• 대한두경부종양학회지
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• 제19권1호
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• pp.34-40
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• 2003

Objective: To analyze the treatment-related parameters after the radiotherapy of T1N0 squamous cell carcinoma of the glottic larynx. Materials and Methods: Between October 1989 and August 2000, 54 patients with histologically proven T1N0 squamous cell carcinoma of the glottic larynx who received definitive radiation therapy in Department of Radiation Oncology, Asan Medical Center were analyzed. They were all males with age ranged from 31 to 80 years (median 61 years). 1997 AJCC stages were 31 T1a, 23 T1b. Patients were treated with 4-MV X-rays with a parallel-opposed two-field technique. Ten patients received 66.0-68.4Gy at 1.2Gy per fraction twice daily, 21 patients received 64.8-66.6Gy at 1.8Gy per fraction once daily, and 23 patients received 66.0Gy at 2.0Gy per fraction once daily. Follow-up period was 16-119 months (median 56 months). Results: 5-year overall survival and local control rates for patients with T1 lesions were 87.0% and 88.5%, respectively. 5-year local control with larynx preservation rate was 90.5%. Host and tumor-related prognostic factors including age, stage, anterior commissure involvement and tumor bulk proved not to be significant. Only shorter overall treatment time among treatment-related factors had correlation with imporved local control. Conclusion: Comparable high local control rate with organ preservation was achieved with primary radiation therapy and salvage surgery. Shortening of overall treatment time is related to improved local control rate. To determine the optimal fractionation scheme, randomized trial is mandatory.

• 방사성폐기물학회지
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• 제17권1호
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• pp.75-94
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• 2019

현재 고려되고 있는 단층 심지층처분장 개념은 부지 소요면적이 지나치게 크기 때문에, 처분밀도를 향상시키기 위한 다층 심지층처분장 개념이 제안되고 있다. 심부암반에 건설된 다층 심지층처분장 주위에 형성된 암반손상대가 심지층처분장의 온도 분포에 미치는 영향이 분석되었다. 다층 심지층처분장의 열해석에는 완충재, 뒤채움재 및 암반에서 일어나는 재포화 현상을 고려한 열-수리 모델이 사용되었다. 암반손상대의 존재는 심지층처분장의 온도 분포에 큰 영향을 미치는 것으로 나타났으며, 손상대의 크기와 열전도도 저하 정도에 따라 복층 및 삼층 심지층처분장의 최고첨두온도를 각각 최대 $7^{\circ}C$와 $12^{\circ}C$까지 증가시킬 수 있다. 다층 심지층처분장의 첨두온도에 영향을 크게 미치는 인자는 암반손상대에서의 열전도도 저하이며, 처분공 주위에 형성된 암반손상대가 처분터널 주변에 형성된 암반손상대보다 첨두온도에 더 큰 영향을 미친다.

• Journal of Korean Neurosurgical Society
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• 제65권2호
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• pp.204-214
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• 2022

Objective : Osteoporosis result from age-related decline in the number of osteoblast progenitors in the bone marrow. Probiotics have beneficial effects on the host, when administered in appropriate amounts. This study investigated the effects of probiotics expressing specific genes, especially the effects of genetically modified bone morphogenetic protein (BMP)-2-expressing Lactobacillus plantarum CJNU 3003 (LP) on ovariectomized rats. Methods : Twenty-eight female Wistar rats (250-300 g, 12 weeks old) were divided into four groups : the sham (control), the ovariectomy (OVX)-induced osteoporosis group (OVX), the OVX and LP (OVX/LP), OVX and genetically modified BMP-2-expressing LP (OVX/LP with BMP) groups. The three groups underwent bilateral OVX and two of these groups were administered two different types of LP via oral gavage daily. At 16 weeks post-OVX, blood was collected from the heart and the bilateral tibiae were extracted and were scanned by ex-vivo micro-computed tomography and stained with hematoxylin-and-eosin (H&E) and Masson's trichrome stain for pathological assessment. The serum levels of osteocalcin (OC), rat C-telopeptide of type I collagen (CTX-I), BMP-2, and receptor activator of nuclear factor-ĸB ligand (RANKL) were measured. Results : The 3D-micro-computed tomography images showed that the trabecular structure in the OVX/LP with BMP group was maintained compared with OVX and OVX/LP groups. No significant differences were detected in trabecular thickness (Tb.Th) between control and OVX/LP with BMP groups (p>0.05). Furthermore, a tendency toward increased BMD, trabecular bone volume, Tb.Th, and trabecular number and decreased trabecular separation was found in rats in the OVX/LP with BMP groups when compared with the OVX and OVX/LP groups (p>0.05). The H&E and Masson's trichrome stained sections showed a thicker trabecular bone in the OVX/LP with BMP group compared with the OVX and OVX/LP groups. There was no difference in serum levels of OC, CTX and RANKL control and OVX/LP with BMP groups (p>0.05). In contrast, significant differences were found in OC and CTX-1 levels between the OVX and OVX/LP with BMP groups (p<0.05). Conclusion : Our results showed that the expression of genetically modified BMP-2 showed inhibition effect for bone loss in a rat model of osteoporosis.

• 생명과학회지
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• 제32권2호
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• pp.94-100
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• 2022

B형간염바이러스(HBV)의 만성 감염은 간경화와 간세포암 발생 빈도를 현저히 높인다. HBV 감염의 임상적 결과는 숙주 유전적 요인과 바이러스의 유전자 변이, 그리고 환경적 요인 등에 결정된다. HBV 복제를 위한 HBV의 pre-genomic RNA 전사는 바이러스의 core promoter 활성화에 의해 조절된다. Core promoter 돌연변이는 급성간 질환과 간세포암 발생에 연관되어 있다. 본 연구팀은 미얀마의 HBV 감염 환자들로부터 바이러스 유전자를 획득하여 core promoter 부위의 유전자 변이들을 파악하였다. Core promoter의 상대적 유전자 활성 차이를 분석하기 위해서 core promoter를 luciferase reporter에 재조합한 시스템을 제작하였다. 분석한 core promoter의 유전자 변이들 중에서 C1731T와 G1806A 돌연변이가 HBV core promoter의 전사 활성화를 증가에 관여하였다. 돌연변이 부위를 중심으로 전사 인자들의 가능한 결합 부위 변화를 컴퓨터 프로그램 분석을 통해 조사한 결과, C/EBPβ와 XBP1 반응 부위가 새롭게 생성되었음을 도출하였다. C/EBPβ의 세포 내 발현은 C1713T 돌연변이를 가진 core promoter의 전사 활성을 증가시켰으며, XBP1 발현은 G1806A 돌연변이를 함유한 M95 promoter를 활성을 증가시켰다. HBV 감염의 치료는 약제 내성과 백신 회피 돌연변이 발생으로 문제점을 가지고 있는 상황에서, 이 연구 결과는 HBV core promoter 돌연변이의 분자생물학적 그리고 임상학적 중요성을 제공한다.

• Journal of Microbiology and Biotechnology
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• 제33권4호
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• pp.552-558
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• 2023

Levulinic acid (LA) is a valuable chemical used in fuel additives, fragrances, and polymers. In this study, we proposed possible biosynthetic pathways for LA production from lignin and poly(ethylene terephthalate). We also created a genetically encoded biosensor responsive to LA, which can be used for screening and evolving the LA biosynthesis pathway genes, by employing an LvaR transcriptional regulator of Pseudomonas putida KT2440 to express a fluorescent reporter gene. The LvaR regulator senses LA as a cognate ligand. The LA biosensor was first examined in an Escherichia coli strain and was found to be non-functional. When the host of the LA biosensor was switched from E. coli to P. putida KT2440, the LA biosensor showed a linear correlation between fluorescence intensity and LA concentration in the range of 0.156-10 mM LA. In addition, we determined that 0.156 mM LA was the limit of LA detection in P. putida KT2440 harboring an LA-responsive biosensor. The maximal fluorescence increase was 12.3-fold in the presence of 10 mM LA compared to that in the absence of LA. The individual cell responses to LA concentrations reflected the population-averaged responses, which enabled high-throughput screening of enzymes and metabolic pathways involved in LA biosynthesis and sustainable production of LA in engineered microbes.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• 제27권1호
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• pp.26-36
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• 2024

Purpose: We investigated the role of CD8⁺T cells as host immune factors in pediatric patients with Helicobacter pylori gastritis. Methods: Gastric mucosal tissue and blood samples were collected from 39 children, including 11 children with H. pylori infection and 28 children as controls. Anti-CD8 and anti-T-bet antibodies were used for immunohistochemistry of the gastric mucosa. For the cell surface and intracellular staining, peripheral blood mononuclear cells were stained with anti-IL7Rα, anti-CX3CR1, anti-CD8, anti-T-bet, and anti-IFN-γ antibodies. Cytokines of sera such as tumor necrosis factor alpha (TNF-α) and CX3CL1 were analyzed using enzyme- linked immunosorbent assay (ELISA). Results: In the immunohistochemistry of gastric mucosa, the frequency of CD8⁺ and T-bet⁺ T cells cells was higher in the H. pylori-positive group than in the control group (26.9± 7.8% vs. 16.9±3.3%, p<0.001; 5.0±2.5% vs. 2.2±0.7%, p=0.001). Between the control and H. pylori-positive groups, the frequency of IL-7Rα^lowCX3CR1⁺ CD8⁺ and T-bet⁺ INF-γ⁺ CD8⁺ T cells were not significantly different between surface and intracellular staining, respectively (40.4±24.0% vs. 38.2±17.8%, p=0.914; 40.4±24.0% vs. 38.2±17.8%, p=0.914). In the ELISA, no significant differences in TNF-α and CX3CL1 concentrations were observed between the control and H. pylori-positive groups (34.3±12.1 pg/mL vs. 47.0±22.6 pg/mL, p=0.114/0.5± 0.1 pg/mL vs. 0.5±0.1 pg/mL, p=0.188). Conclusion: CD8⁺ T and Th1 cells, which secrete IFN-γ, might play important roles in the mucosal immunity of the stomach in children with H. pylori infection.

• Parasites, Hosts and Diseases
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• 제62권1호
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• pp.53-63
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• 2024

The intracellular parasite Babesia microti is among the most significant species causing human babesiosis and is an emerging threat to human health worldwide. Unravelling the pathogenic molecular mechanisms of babesiosis is crucial in developing new diagnostic and preventive methods. This study assessed how priming with B. microti surface antigen 1 (BHSA 1) and seroreactive antigen 5-1-1 (BHSA 5-1-1) mediate protection against B. microti infection. The results showed that 500 ㎍/ml rBMSA1 and rBMSA5-1-1 partially inhibited the invasion of B. microti in vitro by 42.0±3.0%, and 48.0±2.1%, respectively. Blood smears revealed that peak infection at 7 days post-infection (dpi) was 19.6%, 24.7%, and 46.7% in the rBMSA1, rBmSA5-1-1, compared to the control groups (healthy mice infected with B. microti only), respectively. Routine blood tests showed higher white blood cell, red blood cell counts, and haemoglobin levels in the 2 groups (BMSA1 and BMSA5 5-1-1) than in the infection control group at 0-28 dpi. Moreover, the 2 groups had higher serum interferon-γ, tumor necrosis factor-α and Interleukin-17A levels, and lower IL-10 levels than the infection control group throughout the study. These 2 potential vaccine candidate proteins partially inhibit in vitro and in vivo B. microti infection and enhance host immunological response against B. microti infection.

• Journal of Animal Science and Technology
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• 제66권4호
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• pp.663-681
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• 2024

Co-infection with porcine reproductive and respiratory syndrome virus (PRRSV) and Haemophilus parasuis (HPS) has severely restricted the healthy development of pig breeding. Exploring disease resistance of non-coding RNAs in pigs co-infected with PRRSV and HPS is therefore critical to complement and elucidate the molecular mechanisms of disease resistance in Kele piglets and to innovate the use of local pig germplasm resources in China. RNA-seq of lungs from Kele piglets with single-infection of PRRSV or HPS and co-infection of both pathogens was performed. Two hundred and twenty-five differentially expressed long non-coding RNAs (DElncRNAs) and 30 DEmicroRNAs (DEmiRNAs) were identified and characterized in the PRRSV and HPS co-infection (PRRSV-HPS) group. Compared with the single-infection groups, 146 unique DElncRNAs, 17 unique DEmiRNAs, and 206 target differentially expressed genes (DEGs) were identified in the PRRSV-HPS group. The expression patterns of 20 DEmiRNAs and DElncRNAs confirmed by real-time quantitative polymerase chain reaction (RT-qPCR) were consistent with those determined by high-throughput sequencing. In the PRRSV-HPS group, the target DEGs were enriched in eight immune Gene Ontology terms relating to two unique DEmiRNAs and 16 DElncRNAs, and the unique target DEGs participated the host immune response to pathogens infection by affecting 15 immune-related Kyoto Encyclopedia of Genes and Genomes enrichment pathways. Notably, competitive endogenous RNA (ceRNA) networks of different groups were constructed, and the ssc-miR-671-5p miRNA was validated as a potential regulatory factor to regulate DTX4 and AEBP1 genes to achieve innate antiviral effects and inhibit pulmonary fibrosis by dual-luciferase reporter assays. These results provided insight into further study on the molecular mechanisms of resistance to PRRSV and HPS co-infection in Kele piglets.

• 사물인터넷융복합논문지
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• 제10권3호
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• pp.19-24
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• 2024

최근 빅데이터, 클라우드 컴퓨팅, 인공지능 등 대용량 데이터 처리 기술의 발전에 따라 데이터센터와 엔터프라이즈 환경에서 고성능 저장장치에 대한 요구가 증가하고 있다. 특히 저장장치의 빠른 데이터 응답 속도는 전체 시스템 성능을 좌우하는 핵심 요소이다. 이에 NVMe(Non-Volatile Memory Express) 인터페이스 기반 SSD(Solid State Drive)가 주목받고 있으나, 다수 호스트의 대량 데이터 입출력 요청을 동시에 처리하는 과정에서 새로운 병목 현상이 발생하고 있다. SSD는 일반적으로 호스트 요청을 내부 큐에 순차적으로 쌓아 처리하는 방식을 취한다. 이때 긴 전송 길이 요청이 먼저 처리되면 짧은 요청들이 장기간 대기하여 평균 응답 시간이 증가한다. 이 문제를 해결하기 위해 데이터 전송 시간제한과 데이터 분할 전송 방법이 제안되었으나 근본적인 해결책이 되지 못했다. 본 논문에서는 저장장치 내부 데이터 처리 스케줄링 전략인 DQBS(Dual Queue Based Scheduling Scheme)를 제안한다. 이 방식은 이중 큐 기반의 스케줄링 전략으로 하나의 큐에서는 요청 순서를, 다른 큐에서는 전송 길이를 기준으로 데이터 전송 순서를 관리한다. 그리고 요청 시간과 전송 길이를 종합적으로 고려하여 효율적인 데이터 전송 순서를 결정한다. 이를 통해 대기 시간이 긴 요청과 짧은 요청을 균형있게 처리할 수 있어 전체 평균 응답 시간을 단축시킬 수 있다. 실제 시뮬레이션 결과, 제안 기법은 기존 순차 처리 방식 대비 월등히 향상된 성능을 보였다. 본 연구는 고성능 SSD 환경에서 데이터 전송 효율을 극대화하는 스케줄링 기법을 제시하여, 차세대 고성능 저장 시스템의 발전에 기여할 수 있을 것으로 기대된다.

• 한국균학회소식:학술대회논문집
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• 한국균학회 2015년도 춘계학술대회 및 임시총회
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• pp.59-59
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• 2015

Cryptococcus neoformans causes life-threatening meningoencephalitis in humans, but the treatment of cryptococcosis remains challenging. To develop novel therapeutic targets and approaches, signaling cascades controlling pathogenicity of C. neoformans have been extensively studied but the underlying biological regulatory circuits remain elusive, particularly due to the presence of an evolutionarily divergent set of transcription factors (TFs) in this basidiomycetous fungus. In this study, we constructed a high-quality of 322 signature-tagged gene deletion strains for 155 putative TF genes, which were previously predicted using the DNA-binding domain TF database (http://www.transcriptionfactor.org/). We tested in vivo and in vitro phenotypic traits under 32 distinct growth conditions using 322 TF gene deletion strains. At least one phenotypic trait was exhibited by 145 out of 155 TF mutants (93%) and approximately 85% of the TFs (132/155) have been functionally characterized for the first time in this study. Through high-coverage phenome analysis, we discovered myriad novel TFs that play critical roles in growth, differentiation, virulence-factor (melanin, capsule, and urease) formation, stress responses, antifungal drug resistance, and virulence. Large-scale virulence and infectivity assays in insect (Galleria mellonella) and mouse host models identified 34 novel TFs that are critical for pathogenicity. The genotypic and phenotypic data for each TF are available in the C. neoformans TF phenome database (http://tf.cryptococcus.org). In conclusion, our phenome-based functional analysis of the C. neoformans TF mutant library provides key insights into transcriptional networks of basidiomycetous fungi and ubiquitous human fungal pathogens.