• Title/Summary/Keyword: RAD18

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Transcription Factor E2F7 Hampers the Killing Effect of NK Cells against Colorectal Cancer Cells via Activating RAD18 Transcription

  • Bingdong Jiang;Binghua Yan;Hengjin Yang;He Geng;Peng Li
    • Journal of Microbiology and Biotechnology
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    • v.34 no.4
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    • pp.920-929
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    • 2024
  • As a pivotal defensive line against multitudinous malignant tumors, natural killer (NK) cells exist in the tumor microenvironment (TME). RAD18 E3 Ubiquitin Protein Ligase (RAD18) has been reported to foster the malignant progression of multiple cancers, but its effect on NK function has not been mined. Here, the study was designed to mine the mechanism by which RAD18 regulates the killing effect of NK cells on colorectal cancer (CRC) cells. Expression of E2F Transcription Factor 7 (E2F7) and RAD18 in CRC tissues, their correlation, binding sites, and RAD18 enrichment pathway were analyzed by bioinformatics. Expression of E2F7 and RAD18 in cells was assayed by qRT-PCR and western blot. Dual-luciferase assay and chromatin immunoprecipitation (ChIP) assay verified the regulatory relationship between E2F7 and RAD18. CCK-8 assay was utilized to assay cell viability, colony formation assay to detect cell proliferation, lactate dehydrogenase (LDH) test to assay NK cell cytotoxicity, ELISA to assay levels of granulocyte-macrophage colony-stimulating factor (GM-CSF), tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ), and immunofluorescence to detect expression of toxic molecules perforin and granzyme B. High expression of RAD18 and E2F7 was found in CRC tissues and cells. Silencing RAD18 could hamper the proliferation of CRC cells, foster viability and cytotoxicity of NK cells, and increase the secretion of GM-CSF, TNF-α, IFN-γ as well as the expression of perforin and granzyme B. Additionally, ChIP and dual-luciferase reporter assay ascertained the binding relationship between RAD18 promoter region and E2F7. E2F7 could activate the transcription of RAD18, and silencing RAD18 reversed the inhibitory effect of E2F7 overexpression on NK cell killing. This work clarified the inhibitory effect of the E2F7/RAD18 axis on NK cell killing in CRC, and proffered a new direction for immunotherapy of CRC in targeted immune microenvironment.

The Results of Radiation Treatment in Carcinoma of the Uterine Cervix (자궁경암의 방사선치료 성적)

  • Lee, Myung-Za;Kim, Jung-Jin
    • Radiation Oncology Journal
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    • v.3 no.2
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    • pp.95-101
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    • 1985
  • From July 1979 through March 1985,112 patients with carcinoma of the uterine cervix were treated by whole pelvis irradiation and intracavitary radiation with Cs-137. The treatment consisted of 3600rad-5200rad to the whole pelvis by parallel opposing portals, 5 days per week, 180-200rad per day. Parametrial boost with 400-800rad was given in 60 patients. 2 intracavitary Cs-137 radiation using TAO applicator were done with 7-10 days interval. Total treatment times were 40-65 days with average 52 days. Total dose of radiation to point A varied from 6820 to 10500rad with average 8388rad and to point B from 4850 to 6899ra0 with average 5898rad. All patients had follow up from 6 months to 75 months and median follow up of 31 months. $9(8\%)$ had stage $14(12.5\%)$ had stage IIa, $50(44.6\%)$ had stage IIb, $33(29.5\%)$ had stage III, $6(5.4\%)$ had stage IV. 110 patients had squamous cell carcinoma and 2 patients had adenocarcinoma. 5 year actuarial survival rates were $61.8\%$ for the entire group, $84.6\%$ for stage Ib,$77.8\%$ for stage IIa, $56.7\%$ for stage IIb, $60\%$ for stage III, $33.3\%$ for stage IV. RT dose to medial parametrium (point A) below 8000rad resulted in $7/18(38.9\%)$ failure (=death) in contrast to 25/94 $(26.5\%)$ failure with dose over 8000rad. RT dose to lateral parametrium (point B) below 6000ra0 yielded 20/63 $(34.9\%)$ failure compared to $10/49(20.4\%)$ failure with dose over 6000rad. Poor survival group of age were between 40-49 years with failure of $14/41(34.1\%)$. There was no increased failure rate below age of 40 with failure of $2111(13.9\%)$. The results suggest that survival is as good as other published data, and that higher doses over 8000rad to point A and 6000rad to point B should be delivered.

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PCNA Modifications for Regulation of Post-Replication Repair Pathways

  • Lee, Kyoo-young;Myung, Kyungjae
    • Molecules and Cells
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    • v.26 no.1
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    • pp.5-11
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    • 2008
  • Stalled DNA replication forks activate specific DNA repair mechanism called post-replication repair (PRR) pathways that simply bypass DNA damage. The bypassing of DNA damage by PRR prevents prolonged stalling of DNA replication that could result in double strand breaks (DSBs). Proliferating cell nuclear antigen (PCNA) functions to initiate and choose different bypassing pathways of PRR. In yeast, DNA replication forks stalled by DNA damage induces monoubiquitination of PCNA at K164, which is catalyzed by Rad6/Rad18 complex. PCNA monoubiquitination triggers the replacement of replicative polymerase with special translesion synthesis (TLS) polymerases that are able to replicate past DNA lesions. The PCNA interaction motif and/or the ubiquitin binding motif in most TLS polymerases seem to be important for the regulation of TLS. The TLS pathway is usually error-prone because TLS polymerases have low fidelity and no proofreading activity. PCNA can also be further polyubiquitinated by Ubc13/ Mms2/Rad5 complex, which adds an ubiquitin chain onto monoubiquitinated K164 of PCNA. PCNA polyubiquitination directs a different PRR pathway known as error-free damage avoidance, which uses the newly synthesized sister chromatid as a template to bypass DNA damage presumably through template switching mechanism. Mammalian homologues of all of the yeast PRR proteins have been identified, thus PRR is well conserved throughout evolution. Mutations of some PRR genes are associated with a higher risk for cancers in mice and human patients, strongly supporting the importance of PRR as a tumor suppressor pathway.

Implementation of Rapid Application Development Method in the Development of Geographic Information Systems of Industrial Centers

  • Sasmito, Ginanjar Wiro;Wibowo, Dega Surono;Dairoh, Dairoh
    • Journal of information and communication convergence engineering
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    • v.18 no.3
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    • pp.194-200
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    • 2020
  • Cities in Indonesia include diverse scattered industrial centers comprising industries that can sustain the existing economic pace. For industrial data collection, the city government still relies on census that consumes extensive time and money. The public are unfamiliar with industries owing to their lack of industry information; therefore, the market share is not optimal. In addition, the opportunity to procure investors for business development is limited. A Geographic Information System (GIS) is a computer system that can record, store, write, analyze, and display geographical data. Using the Rapid Application Development (RAD) method, GIS was developed on a website platform to provide information on industry profiles, types of production, investment values, industry maps, and industrial locations in each village and sub-district to a wider community. The RAD method was chosen compared to the waterfall method because it could accelerate website development process.

Single Photon Interference Experiments in a Sagnac-type Mach-Zehnder Interferometer (Sagnac 형태로 변형된 Mach-Zehnder 간섭계를 이용한 단일광자 간섭실험)

  • Um, Jayoon;Kim, Yong Soo;Kim, Heonoh
    • Korean Journal of Optics and Photonics
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    • v.23 no.2
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    • pp.71-76
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    • 2012
  • A Sagnac-type Mach-Zehnder interferometer(SMZI) is a very stable instrument with respect to phase drift because all optical paths can share common optical components. We have observed very stable interference fringes in single photon interference experiments with an extremely attenuated laser beam, and with heralded single photons prepared from polarization correlated photon pairs in type-II spontaneous parametric down-conversion. The phase stability is measured to be about ${\pm}0.18$ rad for the SMZI, in contrast, conventional MZI showed the phase fluctuation of around ${\pm}1.02$ rad.

The analysis on the Pulsed radiation effect for semiconductor unit devices (반도체 단위소자의 펄스방사선 영향분석)

  • Jeong, Sang-hun;Lee, Nam-ho;Lee, Min-woong
    • Proceedings of the Korean Institute of Information and Commucation Sciences Conference
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    • 2016.05a
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    • pp.775-777
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    • 2016
  • In this paper presents an analysis of pulsed radiation effects of unit devices. Unit devices are the nMOSFET, pMOSFET, NPN Transistor and those fabricated by the 0.18um CMOS process. Pulsed radiation test results in nMOSFET, the photocurrent of tens nA was generated in $2.07{\times}10^8rad(si)/s$. For the pMOSFET, a photocurrent generation was not observed in $3{\times}10^8rad(si)/s$. For the NPN transistor, the photocurrent was generated with about 1uA. Therefore, the MOSFET must be used than BJT transistor when radhard IC design.

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Identification and Cloning of jipA Encoding a Polypeptide That Interacts with a Homolog of Yeast Rad6, UVSJ in Aspergillus nidulans

  • Cho, Jae-Han;Yun, Seok-Soong;Jang, Young-Kug;Cha, Mee-Jeong;Kwon, Nak-Jung;Chae, Suhn-Kee
    • Journal of Microbiology
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    • v.41 no.1
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    • pp.46-51
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    • 2003
  • RAD6 in yeast mediates postreplication DNA repair and is responsible for DNA-damage induced mutations. RAD6 encodes ubiquitin-conjugating enzyme that is well conserved among eukaryotic organisms. However, the molecular targets and consequences of their ubiquitination by Rad6 have remained elusive. In Aspergillus nidulans, a RAD6 homolog has been isolated and shown to be an allele of uvs). We screened a CDNA library to isolate UVSJ-interacting proteins by the yeast two-hybrid system. JIPA was identified as an interactor of UVSJ. Their interaction was confirmed in vitro by a GST-pull down assay. JIPA was also able to interact with mutant UVSJ proteins, UVSJl and the active site cysteine mutant UVSJ-C88A. The N- and the C-terminal regions of UVSJ required for the interaction with UVSH, a RAD18 homolog of yeast which physically interacts with Rad6, were not necessary for the JIPA and UVSJ interactions. About 1.4 kb jipA transcript was detected in Northern analysis and its amount was not significantly increased in response to DNA-damaging agents. A genomic DNA clone of the jipA gene was isolated from a chromosome I specific genomic library by PCR-sib selection. Sequence determination of genomic and cDNA of jipA revealed an ORF of 893 bp interrupted by 2 introns, encoding a putative polypeptide of 262 amino acids. JIPA has 33% amino acid sequence identity to TIP41 of Saccharomyces cerevisiae which negatively regulates the TOR signaling pathway.

Rectal Injuries after Radiotherapy for Carcinoma of the Uterine Cervix (자궁경암(子宮頸癌) 방사선치료(放射線治療)에 의한 직장손상(直腸損傷))

  • Kim, Jung Jin
    • Radiation Oncology Journal
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    • v.1 no.1
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    • pp.103-109
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    • 1983
  • 47 out of 56 cases of intact uterine cervix cancer treated by radiation at the Hanyang University Hospital were followed 18 months or more after treatment. (7 patients died before 18 months, 2 cases lost to follow-up). Age distribution reveal 5 cases in 30's, 18 cases in 40's, 17 cases in 50's, 7 cases in 60's. Histologically, all cases were squamous cell type except one case of adenocarcinoma. 1. 45 cases were treated by combined external Co-60 irradiation and intracavitary irradiation by Cs-137 small sources. 1 case was treated by external irradiation only, and 1 case by intracavitary only. 2. Rectal injuries were observed in 13 cased (27.6%), 4 cases in Grade 1, 8 cased in Grade 2 and 1 cases in Grade 3 which needed surgical management. 3. Average intervals of rectal injury following treatment was 9.2 months varying from 5 to 15 months. 4. Relation between rectal injury and point A dose reveal 6 cases between 7000-7999 rad and 6 cases between 8000-8999 rad and 1 case above 9000 rad. Even though there is no direct relation between point A dose and rectal injury, it is expected that rectal injury increases as point A dose increase. 5. In the normal condition, rectal injury can't be attributed to one major cause. Radiation dose, small source distribution, general condition of patients, local anatomy of the individual patient, history of PID and previous surgery, all play complex roles.

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Mirror Manipulator with Independent Adjustability Using an External Spherical Joint (외부 구형관절을 이용한 조정 독립형 거울조정기)

  • 길계환;김창균;나승유;이재민;윤화식;윤무현;백성기
    • Journal of the Korean Vacuum Society
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    • v.10 no.2
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    • pp.145-154
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    • 2001
  • A new type of modular mirror manipulator with independent adjustability was developed for the EPU6 beamline under construction at the Pohang Accelerator Laboratory. The mirror manipulator was designed so that the angular displacements of roll and pitch rotations do not introduce translational displacements and are independent with each other by positioning the mirror center to the center of a newly devised spherical joint. Manipulating its roll and pitch micrometers, the rotation angles of a dummy mirror were measured at an accuracy of 5 $\mu$rad using a gravity-referenced inclinometer. While the designed angular resolution was 3.937 $\mu$rad/$\mu\textrm{m}$, measured angular resolutions were 3.94 $\mu$rad/$\mu\textrm{m}$ for roll rotation and 3.85 $\mu$rad/$\mu\textrm{m}$ for pitch rotation. The effect of roll rotation on pitch angles was measured to be -3.18% and the effect of pitch rotation on roll angles was measured to be -5.21%. As the mirror manipulator was designed with emphases on independent adjustability and standardization, it results in eases of manufacturing, installation and adjustment as well as reductions of development period and design cost of mirror manipulators for various types of mirrors.

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COMPARISON OF DEVELOPMENTAL AND PSYCHOPATHOLOGlCAL CHARACTERISTICS FOR RAD AND PDD CHILDREN (반응성 애착장애 아동과 전반적 발달장애 아동의 발달 및 정신병리학적 특징의 비교연구)

  • Yoon, Hyun-Sook;Choi, Jin-Sook;Kim, Tae-Ryeon;Hong, Kang-E
    • Journal of the Korean Academy of Child and Adolescent Psychiatry
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    • v.3 no.1
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    • pp.3-13
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    • 1992
  • For the purpose of better understanding of RAD children, comparisons were performed about the developmental and psychopathological characteristics between RAD and PDD children. Study subjects were the children between the ages 2 and 6. who visitied SNUCH Child and Adolescent Psychiatry OPD or treated in Day Treatment Center during May, 1989 and Sep., 1991, diagnosed by the child psychiatrist as RAD or PDD according to DSM-III-R diagnostic criteria. A total of 40 children were included in the study. 20 were RAD(18 boys, 2 girls). 20 were PDD(20 boys). PEP was performed to all study subjects, by the raters blind to psychiatric diagnosis of each. And analysis was done about the level of developmental functioning score and psychopathological scores between RAD and PDD children. The results are as follows 'There were retardation on the general developmental functioning in RAD children, and the severity of retardation were lined up as perceptual ability>imitation>gross motor>cogitive language>eye-hand coordination>fine motor. Characteristics of psychopathology in RAD children were lined up by severity as language>play>relationship>affection >sensory. Group differences of the two shows on PDD group rejection score was significantly higher on the perception item. while RAD was superior on the perception emerging response. Differences of the psychopathology between two groups were on such areas as ; Affection, which was significantly higher on 'Absent' in RAD, while significantly higher on 'severe' in PDD children. On the interest for the play and materials. sensory and language areas, RAD children were significantly higher ratings on 'Absent' than PDD children.

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