• Title/Summary/Keyword: PI4P

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Convergence of Cancer Metabolism and Immunity: an Overview

  • Van Dang, Chi;Kim, Jung-whan
    • Biomolecules & Therapeutics
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    • v.26 no.1
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    • pp.4-9
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    • 2018
  • Cancer metabolism as a field of research was founded almost 100 years ago by Otto Warburg, who described the propensity for cancers to convert glucose to lactate despite the presence of oxygen, which in yeast diminishes glycolytic metabolism known as the Pasteur effect. In the past 20 years, the resurgence of interest in cancer metabolism provided significant insights into processes involved in maintenance metabolism of non-proliferating cells and proliferative metabolism, which is regulated by proto-oncogenes and tumor suppressors in normal proliferating cells. In cancer cells, depending on the driving oncogenic event, metabolism is re-wired for nutrient import, redox homeostasis, protein quality control, and biosynthesis to support cell growth and division. In general, resting cells rely on oxidative metabolism, while proliferating cells rewire metabolism toward glycolysis, which favors many biosynthetic pathways for proliferation. Oncogenes such as MYC, BRAF, KRAS, and PI3K have been documented to rewire metabolism in favor of proliferation. These cell intrinsic mechanisms, however, are insufficient to drive tumorigenesis because immune surveillance continuously seeks to destroy neo-antigenic tumor cells. In this regard, evasion of cancer cells from immunity involves checkpoints that blunt cytotoxic T cells, which are also attenuated by the metabolic tumor microenvironment, which is rich in immuno-modulating metabolites such as lactate, 2-hydroxyglutarate, kynurenine, and the proton (low pH). As such, a full understanding of tumor metabolism requires an appreciation of the convergence of cancer cell intrinsic metabolism and that of the tumor microenvironment including stromal and immune cells.

A Study on Ultra Precision Machining for Aspherical Surface of Optical Parts (비구면 광학부품의 초정밀 가공에 관한 연구)

  • Lee, Ju-Sang
    • Journal of the Korean Society for Precision Engineering
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    • v.19 no.10
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    • pp.195-201
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    • 2002
  • This paper deals with the precision grinding for aspherical surface of optical parts. A parallel grinding method using the spherical wheel was suggested as a new grinding method. In this method, the wheel axis is positioned at a $\pi$/4 from the Z-axis in the direction of the X-axis. An advantage of this grinding method is that the wheel used in grinding achieves its maximum area, reducing wheel wear and improving the accuracy of the ground mirror surface. In addition, a truing by the CG (curve generating) method was proposed. After truing, the shape of spherical wheel transcribed on the carbon is measured by the Form-Talysurf-120L. The error of the form in the spherical wheel which is the value ${\Delta}x$ and $R{^2}{_y}$ inferred from the measured profile data is compensated by the re-truing. Finally, in the aspherical grinding experiment, the WC of the molding die was examined by the parallel grinding method using the resin bonded diamond wheel with a grain size of #3000. A form accuracy of 0.16${\mu}m$ P-V and a surface roughness of 0.0067${\mu}m$ Ra have been resulted.

English Sounds to Japanese Ears

  • Yuichi Endo
    • Proceedings of the KSPS conference
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    • 2000.07a
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    • pp.47-58
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    • 2000
  • For the learners of English as a foreign language, oral repetition of model sentences is an e essential practice to improve their listening and speaking abilities of English. Skill training of both speech perception and production is involved in this practice. This paper reports on an observation of production e$\pi$ors in such practice made by Japanese college students in my class. The teaching material used is intended for acquainting the learners with basic English rhythm and intonation p patterns. The students were required to repeat each sentence in a series of conversations after a model reading. Although the vocabulary and expressions were rather limited, I monitored different kinds of errors in their repetition. Putting aside intonation, their difficulties are classified into five types; 1. Omission of words or morphemes, 2. Addition of unnecessary words or morphemes, 3. Replacement of words, 4. Japanization of English sounds, 5. Wrong rhythm caused by improper stress assignment. Accurate listening, especially to weakly stressed syllables and to assimilated sounds, as has often been pointed out, is the most difficult part in perception for them. Japanese sound system interferes in production of English sounds. More often than not their knowledge of grammar or the context does not work at all to guess the words they are hearing

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Automatic Tension Control of a Timber Carriage Used for Biomass Collection

  • Choi, Yun-Sung;Oh, Jae-Huen;Euh, Seung-Hee;Oh, Kwang-Cheor;Choi, Hee-Jin;Kim, Dae-Hyun
    • Journal of Biosystems Engineering
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    • v.37 no.2
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    • pp.106-112
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    • 2012
  • Purpose: A lab-scale timber carriage using a servo motor system was built. When two motors move a carriage, wire tension is changed according to the different line speeds caused by a wire drum's changing diameter, leading to inappropriate traveling characteristics of the carriage. In order to overcome this problem, PID Control was used to control the motor speed. Methods: Ziegler-Nichols method was used to determine PID gains. Results: The initial PID gains were 1.8, 0.025, and 0.006, respectively, and optimal gains of 1.4 and 0.010 for P and I gain were obtained experimentally. Conclusions: The results showed that constant wire tension could be maintained by controlling the speed of the motor using PI control. Overshoot occurred at initial motor operation due to vibration and elasticity of the wire itself.

The Reaction Probability and the Reaction Cross-section of N + O2→ NO + O Reaction Computed by the 6th-order Explicit Symplectic Algorithm

  • He, Jianfeng;Li, Jing
    • Bulletin of the Korean Chemical Society
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    • v.27 no.12
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    • pp.1976-1980
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    • 2006
  • We have calculated the reaction probability and the reaction cross-section of the $N(^4S)+O_2(X^3\sum_{g}^{-})\;\rightarrow\;NO(X^2\Pi)+O(^3P)$ reaction by the quasiclassical trajectory method with the 6th-order explicit symplectic algorithm, based on a new ground potential energy surface. The advantage of the 6th-order explicit symplectic algorithm, conserving both the total energy and the total angular momentum of the reaction system during the numerical integration of canonical equations, has firstly analyzed in this work, which make the calculation of the reaction probability more reliable. The variation of the reaction probability with the impact parameter and the influence of the relative translational energy on the reaction cross-section of the reaction have been discussed in detail. And the fact is found by the comparison that the reaction probability and the reaction cross-section of the reaction estimated in this work are more reasonable than the theoretical ones determined by Gilibert et al.

Effect of Ginseng Saponins on $K^+-Dependent$ Phosphatase Activity of Dog Cardiac Sarcolemma (인삼 사포닌이 개 심실 형질막의 $K^+$-의존성 포스파타제 활성에 미치는 영향)

  • Lee, Shin-Woong;Lee, Jeung-Soo
    • YAKHAK HOEJI
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    • v.36 no.2
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    • pp.129-136
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    • 1992
  • The effects of ginseng saponins, gypsophila saponin, sodium dodecyl sulfate(SDS), and Triton X-100 on membrane $K^+-dependent$ phosphatase activity which is lipid dependent and represents dephosphorylation step of the complete Na+, $K^+-ATPase$ reaction were investigated in this study to elucidate whether the effects of ginseng saponins are due to the detergent action, using sarcolemma enriched preparation isolated from dog ventricle. $Na^+$, $K^+-ATPase$ and $K^+-dependent$ phosphatase activities of cardiac sarcolemma were about $143\;{\mu}mol$ Pi/mg protein/hr and $34\;{\mu}mol$ p-nitrophenol/mg protein/hr, respectively. While ginseng saponins (triol>total>diol) inhibited $K^+-dependent$ phosphatase activity, gypsophila saponin, and low dose of SDS($0.4\;{\mu}g/{\mu}g$ protein), and Triton X-100 ($0.6\;{\mu}g/{\mu}g$ protein) increased the enzyme activity, indicating disruptive effect of detergents on membrane barriers. The activating effect of low doses of Triton X-100 on membrane $K^+-dependent$ phosphatase appeared at concentration decreasing light scattering. However, the inhibitory effect of ginseng saponin appeared before a decrease in light scattering. These results suggest that low concentrations of ginseng saponins inhibit the membrane $K^+-dependent$ phosphatase by interacting directly with enzyme before membrane disruption.

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Assessment of DNA Ploidy Patterns in Connection with Prognostic Factors in Patients with Papillary Thyroid Carcinoma (유두상 갑상선암에서 예후인자와 DNA배수성의 상관관계)

  • Chung Woung-Youn;Lee Jong-Hoon;Park Cheong-Soo
    • Korean Journal of Head & Neck Oncology
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    • v.12 no.2
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    • pp.153-160
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    • 1996
  • Regardless of the prognostic factors in papillary thyroid cancer, such as sex, age, size of tumor, extent of disease, and distant metastasis, the prognosis of papillary thyroid cancer is sometimes difficult to predict from clinical and microscopic analysis alone and additional prognostic indicators are needed. Recent studies of thyroid cancer have indicated that DNA aneuploidy may be correlated to the biological behavior of malignancy and inversely correlated to the prognosis, but it still remains contraversal. We performed this study to assess DNA ploidy patterns in relation with the previously known prognostic factors in AMES scoring system and lateral neck node metastasis in papillary thyroid cancer. A series of 132 patients with papillary thyroid cancer and 80 patients with benign thyroid tumor(27 follicular adenomas and 53 adenomatous goiters) as a control group from October 1993 to Feburary 1995 were analyzed and their nuclear DNA content was measured with flow cytometry using fresh tissue specimens. DNA aneuploidy was found in 8(6.1%) in papillary cancer and 8(10%) in benign tumor. S-phase traction(SFP) and proliferative index(PI) were higher in thyroid cancers, being 2.18$\pm$4.24%, 6.34$\pm$4.94% in the papillary thyroid cancers and 1.97$\pm$2.93%, 4.44$\pm$3.80% in the benign tumors, respectively. However there was no significant difference of values between two groups(p>0.05). Among variable prognostic factors studied(age, sex, size of tun or, extent of disease, distant metastasis in AMES scoring system and lateral neck node metastasis), DNA aneuploidy was found to be common in distant metastasis(p<0.001) and in lateral neck node metastasis(p>0.035), but there was no significant difference between the high risk and low risk group according to the AMES scoring system(p<0.08). In our study, DNA aneuploidy was not valuable in determining the presence of malignancy and did not correlate to the AMES scoring system. However, follow-up study of more cases will be needed for accurate information about the DNA ploidy as a independent prognostic factor.

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Effect of Ovary Transport Temperature on Survivability and Maturation Rate of Canine Oocytes (개 난소 수송온도에 따른 미성숙 난자의 생존율과 핵 성숙율)

  • 이효상;윤희준;이영호;공일근
    • Journal of Embryo Transfer
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    • v.18 no.2
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    • pp.85-90
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    • 2003
  • This study examined the viability of canine oocytes following storage at 4 or 38$^{\circ}C$ for 5 h. Cumulus intact oocytes were collected from domestic dog following ovariohysterectomy at local veterinary clinics. In Exp I, the oocytes that collected from ovary transport different temperatures (4 or 38$^{\circ}C$) for 5 h, were cultured for (24 or 48 h). Survivability of oocytes judged by morphological appearance and PI (propidium iodide) staining. The survival rates at 4$^{\circ}C$ ovary transport group showed significantly lower than control group (0%; 0/129 vs. 72.9%; 129/177) 48 h after culture (P<0.05). In Exp II, to assess nuclear maturation of control group oocytes (ovary transported at 38$^{\circ}C$) after in vitro cultured for 24, 48 or 96 h. After 24 h and 48 h of culture, the metaphase I to metaphase II stages (MI to MII) was 8.3% (6/72) and 8.9% (9/101), and which was not increased at 96h (9.5%; 8/84). These results show that canine oocytes remarkably sensitive to low temperature and the percentage of oocytes reaching MI to MII did not increase 96 h after culture.

KAT8/MOF-Mediated Anti-Cancer Mechanism of Gemcitabine in Human Bladder Cancer Cells

  • Zhu, Huihui;Wang, Yong;Wei, Tao;Zhao, Xiaoming;Li, Fuqiang;Li, Yana;Wang, Fei;Cai, Yong;Jin, Jingji
    • Biomolecules & Therapeutics
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    • v.29 no.2
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    • pp.184-194
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    • 2021
  • Histone acetylation is a well-characterized epigenetic modification controlled by histone acetyltransferases (HATs) and histone deacetylases (HDACs). Imbalanced histone acetylation has been observed in many primary cancers. Therefore, efforts have been made to find drugs or small molecules such as HDAC inhibitors that can revert acetylation levels to normal in cancer cells. We observed dose-dependent reduction in the endogenous and exogenous protein expression levels of KAT8 (also known as human MOF), a member of the MYST family of HATs, and its corresponding histone acetylation at H4K5, H4K8, and H4K16 in chemotherapy drug gemcitabine (GEM)-exposed T24 bladder cancer (BLCA) cells. Interestingly, the reduction in MOF and histone H4 acetylation was inversely proportional to GEM-induced γH2AX, an indicator of chemotherapy drug effectiveness. Furthermore, pGL4-MOF-Luc reporter activities were significantly inhibited by GEM, thereby suggesting that GEM utilizes an MOF-mediated anti-BLCA mechanism of action. In the CCK-8, wound healing assays and Transwell® experiments, the additive effects on cell proliferation and migration were observed in the presence of exogenous MOF and GEM. In addition, the promoted cell sensitivity to GEM by exogenous MOF in BLCA cells was confirmed using an Annexin V-FITC/PI assay. Taken together, our results provide the theoretical basis for elucidating the anti-BLCA mechanism of GEM.

Impact of HER2 and PTEN Simultaneous Deregulation in Non-small Cell Lung Carcinoma: Correlation with Biological Behavior

  • Panagiotou, Ioannis;Georgiannos, Stavros N.;Tsiambas, Evangelos;Karameris, Andreas;Konstantinou, Marios;Lazaris, Andreas C.;Kavantzas, Nikolaos;Vilaras, George;Patsouris, Efstratios
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.12
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    • pp.6311-6318
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    • 2012
  • Background: HER2/neu overexpression due to gene amplification is an important factor in breast cancer, modifying the sensitivity to anti-HER2 monoclonal antibody therapy. The clinical significance of HER2 expression in non small cell lung carcinoma (NSCLC) is currently under evaluation. The tumor suppressor gene PTEN negatively regulates the HER2/PI3K/Akt signalling pathway. The purpose of this study was to evaluate the role of simultaneous alteration in HER2 and PTEN protein expression in relation to biological behaviour of NSCLCs. Materials and Methods: Protein expression was determined by immunohistochemistry in sixty-one (n=61) NSCLC cases along with CISH for HER2 gene analysis and detection of chromosome 17 aneuploidy. Patients were followed-up for a period of 34 to 41 months after surgery. Results: HER2 overexpression (2+/3+score) was detected in 17 (27.9%) patients while loss of PTEN expression was observed in 24 (39.3%) cases, low expression in 29 (47.6%) and overexpression in 8 (13.1%). Simultaneous HER2 overexpression and PTEN low/loss of expression were correlated with metastasis (71.4% vs 36.2% p=0.03). Analysis in the subgroup of 22 patients of pTNM stage III with lymph node status N1 or N2 revealed that there was a relationship between the number of positive regional lymph node groups and simultaneous deregulation of the two genes (p=0.04). Multivariate analysis determined that HER2 overexpression was associated with an increasing risk of developing metastases (OR: 4.3; 95%CI: 1.2-15.9; p: 0.03) while PTEN overexpression was associated with lower risk (OR: 0.1; 95%CI: 0.1, 1.0; p: 0.05). Conclusions: Simultaneous HER2/PTEN deregulation is a significant genetic event that leads to a more aggressive phenotype of NSCLC.