Development of pentaplex RT-ddPCR assay for detecting HIV-1, HIV-2, HCV, HBV, and internal control

Lim, Sooyeon Sungkyunkwan University 2025 국내석사

The primary goal of this study is to develop a novel technology to ensure the safety of biological reference materials, particularly blood-derived reference materials. According to the WHO, blood products and reference materials for blood-borne pathogens such as HIV-1, HIV-2, HCV, and HBV require continuous validation to guarantee their integrity. Therefore, rigorous verification of blood-borne viruses is essential. The secondary goal is to propose a novel auxiliary diagnostic method. Most commercially available viral nucleic acid diagnostic kits rely on antigen-antibody tests or single-target real-time PCR (qPCR). However, accurate quantification of nucleic acids is crucial for virus diagnosis to determine the stage of infection and the success of antiretroviral therapy, which highlights the limitations of applying multiplex qPCR. qPCR requires a standard curve as the basis for quantification, and commercial kits utilizing this technology face challenges in absolute comparison and performance validation across different platforms. To overcome these limitations, this study employed ddPCR, an absolute quantification method that eliminates the need for a standard curve while offering high sensitivity and strong resistance to inhibitors. In this assay, the 95% detection limit for HIV-1, HIV-2, HCV, and HBV was validated at ≤5 copies/reaction, and high specificity was demonstrated for all targets. Robustness and precision tests showed low coefficients of variation (CV%), establishing the reliability of the assay. Furthermore, consistent detection of the internal control enabled the identification of false negatives. This study validated the ddPCR-based pentaplex detection method using international reference materials; however, several limitations remain, including the fact that it has not yet been applied to actual clinical samples. Nevertheless, it is significant that this study proposed a novel approach by integrating pentaplex RT-ddPCR into the screening and diagnostic fields, paving the way for future clinical sample research. 본 연구의 첫 번째 목표는 생물학적 표준물질 중에서도 혈액 유래 표준물질의 안 전성을 보장하기 위한 새로운 기술을 개발하는 것이다. WHO에 따르면, 혈액 제제 및 HIV-1, HIV-2, HCV, HBV와 같은 혈액 매개 병원체 표준물질은 그 무결성을 보장하기 위해 지속적인 검증이 필요하다. 따라서, 혈액 매개 바이러스에 대한 엄격 한 검증이 필수적이다. 두 번째 목표는 새로운 보조 진단 방법을 제안하는 것이다. 대부분의 상용화된 바이러스 핵산 진단 키트는 항원-항체 검사 또는 단일 타겟 real-time PCR(qPCR) 에 의존하고 있다. 하지만 바이러스 진단에는 감염 단계와 항레트로바이러스 치료 성공 여부를 판단하기 위한 핵산 정량이 필요하며, 이는 멀티플렉스 qPCR 적용에 서의 한계를 드러낸다. qPCR은 정량의 기준이 되는 standard curve를 필수적으로 요구하고, 해당 기술 을 사용하는 상용화된 키트들은 서로 간의 절대적인 비교와 성능 검증이 어렵다는 한계점이 있다. 이러한 한계를 극복하기 위해, 본 연구에서는 표준 곡선이 필요 없 는 절대정량법을 이용하며, 억제제에 강하고 민감도가 높은 ddPCR을 사용하였다. 본 assay에서 HIV-1, HIV-2, HCV, HBV에 대한 95% 검출한계는 ≤5 copies/reaction으로 검증되었으며, 모든 타겟에 대해 높은 특이성이 입증되었다. 견 고성과 정밀성 테스트에서는 낮은 변동계수(CV%)가 관찰되어 assay의 신뢰성이 확립되었다. 또한 Internal control의 일관된 검출을 통해 위음성을 식별했다. 본 연구에서는 ddPCR 기반의 pentaplex assay를 국제 표준물질로 검증하였으나, 실제 임상 샘플에 적용해 보지 못했다는 사실을 포함한 몇 가지 한계점이 남아 있 다. 하지만, 스크리닝과 진단 분야에 pentaplex RT-ddPCR를 접목하는 새로운 방법 을 제시하여 향후 임상 샘플 연구를 위한 시도를 했다는 사실에 의의가 있다.

Controlled synthesis and assembly of anisotropic metal nanostructures for stretchable electronic devices

Lim, Guhhwan Sungkyunkwan university 2018 국내박사

Advances in the field of wearable devices are largely dependent on the development of an effective strategy for fabricating stretchable electrodes. In addition to metallic conductivity and high stretchability, good electromechanical stability is required for stretchable electrodes to achieve reliable performance. An alternative strategy is to integrate one-dimensional conductive nanomaterials such as anisotropic metal nanostructures on or within a stretchable elastomeric substrate to form a percolating network that can provide an electrical pathway upon stretching. Despite recent progress, it remains a challenging task to produce highly stretchable and durable network films and devices based on anisotropic metal nanostructures via a simple manufacturing process. Here, we describe a simple, aqueous-phase route to synthesize anisotropic metal nanostructures via solution-phase synthetic methods. We found that multiple-twinned silver (Ag) seeds are generated preferentially at the nucleation stage of the heat-up synthesis, and then grow into long nanowires (NWs) with an average length of about 20 lm. We were also able to produce Ag nanoplates with an average lateral size larger than 1 μm and gold (Au) nanosheets with an average lateral size larger than ~50 μm. Furthermore, we firstly prepared stretchable Au electrodes made of multilayers of Au nanosheets. The electrodes patterned on a rubber substrate showed highly stretchable electromechanical properties under large strain levels (ε ≈ 60%). We also discovered that Ag NWs can be elastically deformed into curved structures within micrometer-sized liquid droplets generated during the spraying process due to the elasto-capillary interaction. By exploiting this curving phenomenon, we were able to directly produce percolating networks made entirely of Ag NW rings on arbitrary substrates, which could be readily embedded in an elastomeric substrate to fabricate stretchable electrodes. Finally, we demonstrated the fabrication of stretchable, highly sensitive, tunable, and durable strain sensors made of multilayered Au nanosheet films for the detection of various human activities. The sensor was simply fabricated by stacking Au nanosheet multilayers on an elastomeric Ecoflex substrate. We also successfully fabricated a fully stretchable and durable triboelectric nanogenerator based on Au nanosheet-embedded electrodes for human motion detection. 최근 착용형 전자 장치에 대한 관심으로 인하여 유연하고 신축성 있는 웨어러블 장치를 만드는 것을 목표로 플렉서블 디스플레이, 신축성 회로, 인공 전자 스킨 및 센서와 같은 차세대 애플리케이션이 주목받고 있다. 웨어러블 장치의 구현을 위해서는 장치를 구성하는 각각의 요소들이 유연 및 신축 가능해야 하며, 특히 소자구동에 필수적인 전극은 유연 및 신축성이 우수해야만 한다. 지금까지 보고된 대부분의 웨어러블 소자들은 Au, Al 또는 Cu와 같은 비신축성 금속 필름이 전극으로써 사용되었기 때문에 유연성 또는 신축성이 부족하다. 이에 기계적/전기적 특성이 우수하고 대량 생산이 용이하며, 용액 공정이 가능한 비등방성 금속 나노소재 기반 신축 소재 및 소자 기술이 큰 관심을 받고 있다. 본 학위논문에서는, 신축 소자용 비등방성 금속 나노소재를 합성하고, 이를 기반으로 우수한 기계적/전기적 내구성을 갖는 신축 전극 제조 기술을 설계하고 개발하였다. 또한, 비등방성 금속 나노소재 신축 전극 기반 스트레인 센서 및 신축 마찰전기 발전소자로의 새로운 응용분야에 대한 연구를 진행하였다. 먼저 용액상 합성 방법을 통해 신축 전극 및 소자용 비등방성 금속 나노소재의 합성 기술을 개발하였다. 폴리올 합성법에 Heat-up 방법을 적용하는 은 씨앗 조절 기술을 통하여 약 ~20 μm의 평균 길이를 갖는 은 나노와이어 합성 기술을 개발하였다. 또한 수용액상 합성법을 통하여 평균 ~1 μm의 측면 크기를 갖는 은 나노플레이트 합성 기술과 생체분자인 아미노산을 이용하여 평균 ~50 μm의 측면 크기를 갖는 금 나노시트 합성 기술을 개발하였다. 다음으로 비등방성 금속 나노소재 기반 신축 전극 설계 및 제조기술 개발 연구를 진행하였다. 랑뮤어-블라짓 막의 일종인 Floating 방법을 이용하여 금 나노시트 기반 신축 전극 기술을 개발하였다. 다층으로 만들어진 신축성 금 나노시트 전극은 60%의 변형률, 10,000 번의 내구성 테스트에서 전도도가 일정하게 유지되는 우수한 기계적/전기적 내구성을 보였다. 또한 간단한 스프레이 코팅을 사용하여 용매의 표면장력만으로 은 나노와이어 링 네트워크를 구현하였으며, 30%의 변형률, 5,000번의 내구성 테스트에서 전도도가 일정하게 유지되는 우수한 기계적/전기적 내구성을 보여주었다. 마지막으로, 우리는 비등방성 금속 나노소재 기반 신축 소자를 설계하고 개발하는 연구를 진행하였다. 유연하고 신축성있는 소자를 제작하기 위해서는 반복적인 외부변형에 대해 기계적으로 견고하며 전기적으로 안정적이고 신뢰성이 우수한 유연 신축 전극의 개발이 선행되어야 한다. 이에 신축성 있는 고감도 금 나노시트 신축 전극 기반 스트레인 센서를 구현하고 다양한 인체활동의 탐지 및 구별 가능성을 보여주었다. 또한 금 나노시트-임베디드 전극을 기반으로 하는 신축성 마찰전기 발전소자를 설계하고 성공적으로 구현하였으며, 구동 메커니즘을 분석하였다. 본 연구 결과는 차세대 웨어러블 소자의 실용화를 앞당기기 위한 우수한 결과로 사료되며, 앞으로도 다양한 연구분야에 활용될 것으로 기대된다.

Explainable Deep Supervised Leaning-based Biological Age Estimation with Risk Score

Dongcheol Lim Ulsan National Institute of Science and Technology 2023 국내석사

The pursuit of immortality and longevity without illness has been a longstanding aspiration of humanity. Since the accurate assessment and management of individuals' current health status is a fundamental step in achieving human wellness, the advancements of health indices remain ongoing endeavors. Recently, several machine learning or deep learning methods have been proposed to estimate biological age (BA) by predicting chronological age or extracting latent representations of health data. However, most previous studies cannot reflect disease information, one of the most important health risk factors, and have also been deficient in clarifying the variable’s importance for BA estimation. Therefore, in this study, we propose a deep supervised learning-based BA estimation method with an explainable autoencoder by reflecting both individuals’ health risk status and disease prevalence to extract latent embeddings. To be specific, we present a self-one-to-one correspondence layer with a Lasso loss function adopted for autoencoder architecture to enhance the model’s interpretability. In addition, we use a supervised loss to predict disease incidence as well as reconstruction loss of the autoencoder to comprehensively represent both a person’s health data and its transformed information with respect to risk. We believe that the proposed method offers a useful solution for improving the explainability and accuracy of BA estimation and contributes to leading personalized health management.

Framework for Feasibility Study of Low-Carbon Ammonia Utilization Strategies in the Energy Sector : Stochastic Optimization, Techno-Economic Analysis, and Machine Learning Predictions

Dongjun Lim Ulsan National Institute of Science and Technology 2024 국내박사

Clinical Nutritional Approach to Human Studies on Health Functional Foods

손금희 경희대학교 대학원 2023 국내박사

A Study on the Assessment of Nutritional Adequacy and the Effects of Lettuce (Lactuca sativa L.) Extracts on Sleep Quality Improvement in Korean Adults with Poor Sleep Quality by Kumhee Son Doctor of Philosophy in Medical Nutrition Graduate School of East-West Medical Science, Kyung Hee University Advised by Dr. Hyunjung Lim Background & Aims: “Coronasomnia” is a newly coined word as sleep problems during the pandemic. Lettuce (Lactuca sativa L.) has been known to contain hypnotic substances that induce sleep. The purposes of this study are to evaluate the effect of lettuce extract on the adults who have poor sleep quality, and to assess the nutritional adequacy of those with poor sleep quality. Methods: This is a randomized, double-blind, and placebo-controlled study from February 2021 to February 2022. Subjects aged from 30 to 65 who had poor sleep quality (Pittsburgh Sleep Quality Index (PSQI) > 5) were enrolled. The subjects took 2 capsules of test or placebo every day for 4 weeks. PSQI, insomnia severity index (ISI), Epworth sleep scale (ESS), Stanford sleep scale (SSS) were measured to assess sleep quality. Actigraphy, sleep diary, and polysomnography (PSG) were used to assess sleep quantity. In addition, to assess sleep related symptoms, depression, anxiety, and fatigue were measured. Dietary intake during the study period was analyzed through 3-day food diary. The nutritional adequacy was analyzed by comparing with the estimated average requirement (EAR) from 2020 Dietary Intakes for Koreans (KDRIs). Also, biochemical measurement, and adverse events were investigated for safety assessment. Results: Among the indices of sleep quality, the amount of changes in PSQI showed significant difference between the test and placebo group (daytime dysfunction: -0.87 ± 0.80 vs. -0.48 ± 0.82, p = 0.0221; global score: -4.91 ± 3.30 vs. -3.55 ± 2.66, p = 0.0328). The amount of changes in SSS showed significant difference between the test and placebo group (-0.66 ± 0.92 vs. -0.18 ± 1.02, p = 0.0206). Among the indices of sleep quantity, total sleep time (actigraphy: 27.48 ± 59.09 min vs. -8.26 ± 59.69 min, p = 0.0051; sleep diary: 32.11 ± 40.62 min vs. 14.20 ± 37.63 min, p = 0.0320) , sleep efficiency (PSG: 4.81 ± 9.53 % vs. -4.74 ± 12.06 %, p = 0.0103), and wake after sleep onset (PSG: -19.55 ± 32.59 min vs. 18.50 ± 39.16 min, p = 0.0025) improved significantly in the test group compared to the placebo group. In addition, the depression, anxiety, and fatigue symptoms improved after 4 weeks in the test group, whereas there was no significant difference in fatigue symptoms in the placebo group. As a result of evaluating nutritional adequacy, it was found that the intake of vitamin D (41.4 ± 40.3%) and magnesium (33.2 ± 14.2%) were insufficient compared with the EAR. Although there was no difference in nutritional adequacy according to severity of poor sleep quality, BMI was higher in the group with worse sleep quality. Conclusion: Lettuce extract showed possibility of improving sleep quality and quantity in the test group compared with the placebo group. As safety was also identified, it suggests that the lettuce extract can be an effective functional food to improve sleep quality. In addition, this study also showed that clinical nutritional intervention is necessary to improve sleep quality through nutritional adequacy assessment of people with poor sleep quality in Korea. Effects of Lotus and Turmeric Complex Extracts with Medical Nutrition Therapy on Blood Lipid Level in Adults with Borderline Dyslipidemia by Kumhee Son Doctor of Philosophy in Medical Nutrition Graduate School of East-West Medical Science, Kyung Hee University Advised by Dr. Hyunjung Lim Background & Aims: Lotus and turmeric extracts has been reported to have lipid-lowering effect. Medial nutrition therapy (MNT) is essential for dyslipidemia management. This study aimed to examine the effects of the lotus and turmeric complex (LTC) extracts with MNT on blood lipide levels in adults with borderline dyslipidemia in Korea. Methods: This is randomized, single-blind, and placebo-controlled study. Subjects aged from 20 to 60 with borderline dyslipidemia were enrolled. They were randomly assigned to 4 groups; Placebo (P) group, Placebo with MNT (PM) group, Test (T) group, Test with MNT (TM) group. To evaluate the effect of intervention, anthropometric measurement, blood lipid profile, dietary intakes were investigated. Results: MNT was only effective in subjects who took placebo. Changes of dietary intake such as energy (P: 215.0 ± 606.2 kcal/day; PM: -394..9 ± 542.1 kcal/day, p = 0.0041), carbohydrate (P: 23.9 ± 87.2 g/day; PM: -52.3 ± 66.2 g/day, p = 0.0073), fat (P: 7.6 ± 36.4 g/day; PM: -15.5 ± 59.6 g/day, p = 0.0212), and protein (P: 8.3 ± 27.1 g/day; PM: -15.3 ± 26.8 g/day, p = 0.0159), waist circumference (P: 091 ± 2.36 cm; PM: -2.18 ± 2.33 cm, p = 0.0006) and hip circumference (P: 0.87 ± 1.57 cm; PM: -0.92 ± 2.49 cm, p = 0.0174), triglyceride (P: 32.8 ± 61.5 mg/dL; PM: -13.1 ± 56.6, p = 0.0302) and high-density lipoprotein cholesterol (HDL-C, P: -3.1 ± 9.5 mg/dL; PM: 3.4 ± 7.8 mg/dL, p = 0.0373) were significantly larger in the group PM than P (p < 0.005). LTC was only effective in subjects who did not undertake MNT. The change of HDL-C (P: -3.06 ± 9.49 mg/dL; PM: 5.06 ± 6.43 mg/ dL, p = 0.0075) was bigger of group T than P. Conclusion: This study was performed to evaluate the effect of the LTC extract on blood lipid levels in combination with MNT in adults with borderline dyslipidemia in Korea. Dietary intake, anthropometric measurements and blood lipid profile were improved only in the MNT with placebo combination group. LTC only influenced HDL-C improvement in group that did not perform MNT.

Structure Elucidation and Mechanisms of Anti-Cancer Steroidal Saponins in Solanum nigrum Leaves

Hyeon-Su Lim 충북대학교 일반대학원 2025 국내석사

This research examines the anticancer potential of steroidal saponins derived from Solanum nigrum leaves. It aims to develop new therapies to address challenges such as drug resistance and toxicity in standard cancer treatments. By focusing on the bioactive potential of these compounds, this study isolates steroidal saponins from S. nigrum and investigates their therapeutic effects. To optimize steroidal saponin extraction, various solvent systems were tested, and multivariate analysis of compound intensities across extracts revealed that 70% aqueous organic solvents efficiently extracted furostanol-type saponins, while 30% aqueous organic solvents favored spirostane-type saponins. The 70% acetone extract was further subjected to sequential separation by liquid-liquid extraction, column chromatography with macroporous and silica gel resins, and preparative liquid chromatography guided by bioactivity fractionation to investigate the anticancer activity of furostanol-type saponins. This approach yielded five compounds (SN1–SN5). Among these, SN1 and SN2 were identified as solamargine and protodioscin through comparison with authentic standards, while SN3, SN4, and SN5 were characterized by MS and NMR as (25S)-uttroside B, (25R)-uttroside B, and (25S)-26-O-β-D-glucopyranosyl-22-hydroxyfurostan-3-O-α-D-rhamnopyranosyl-(1→2)-[α-D-xylopyranosyl-(1→2)-[β-D-xylopyranosyl-(1→3)]-β-D-glucopyranosyl-(1→4)-β-D-galactopyranoside, with SN3 and SN5 being reported here for the first time. The anticancer potential of the isolated saponins was further investigated, with a particular focus on SN5. In HeLa cell assays, SN5 exhibited notable effects by inhibiting cell proliferation and migration, inducing G2/M phase cell cycle arrest, and promoting apoptosis. A metabolomic analysis was conducted to elucidate the underlying mechanisms of SN5’s anticancer activity. Results indicated that SN5 impacted arginine metabolism pathways, suggesting a metabolic mechanism through which SN5 exerts its anticancer effects. Collectively, these findings highlight the therapeutic potential of steroidal saponins from S. nigrum, especially in the context of cervical cancer, and underscore the importance of further research to fully explore their mechanisms of action.

MOS Switch를 이용한 Negative Skewed Ring Oscillator

임장진 부경대학교 대학원 2002 국내석사

Subcritical Water Extraction and Hydrolysis of Citrus Flavonoids : Kinetics, Optimization, and Biological Activities

Kim,Dong-Shin 제주대학교 2020 국내박사

Citrus peels are the main source of many important flavonoids, flavanones (hesperidin and narirutin) and polymethoxyflavones (PMFs; sinensetin, nobiletin, and tangeretin), which have antioxidant, anti-inflammatory, anticancer, and cardioprotective properties. In part 1, the mechanisms controlling the extraction rates of flavonoids from Citrus unshiu peel using subcritical water (SW) were studied at different temperatures (120−180 °C) and flow rates (1.0−2.0 mL/min). The extraction yields increased from 40.9, 69.0, and 67.4% at 120 °C to 79.6, 81.9, and 89.0% at 160 °C for hesperidin, narirutin, and PMFs, respectively, while decomposition occurred at 180 °C. The extraction rate curves at different flow rates were used to determine whether the extraction was best described by a thermodynamic partitioning or kinetic desorption model. The extraction rate curves showed that the initial extraction phase is fast, while the subsequent phase is slow. The thermodynamic partitioning model did not match with the experimental data for the latter part of the extraction period. The two-site kinetic desorption model fits the entire extraction period very well, suggesting that the extraction of citrus flavonoids was mainly controlled by intra-particle diffusion. Interestingly, this model fits well even at the pyrolysis temperature (180 °C). Therefore, the two-site kinetic model well described both the decomposition and extraction mechanism of citrus flavonoids when using SW. The diffusion coefficient of hesperidin increased about 9.8-fold at 160 °C and 2 mL/min relative to 120 °C and 1 mL/min. The activation energy of hesperidin (37.2−43.8 kJ/mol) was higher than those of narirutin and PMFs (8.2−36.8 kJ/mol). The use of small amounts of SW, an environmentally friendly solvent, promotes good recovery of flavonoids from citrus peel in a short time. In part 2, citrus flavonoids were extracted and hydrolyzed from Citrus unshiu peel using SW. The individual flavonoid yields, antioxidant and enzyme inhibitory activities of the SW extracts were analyzed. The extraction yields of hesperidin and narirutin increased with increasing temperature from 145 °C to 165 °C. Hydrothermal hydrolysis products (HHP), such as monoglucosides (hesperetin-7-O-glucoside and prunin) and aglycones (hesperetin and naringenin) were obtained in the SW extracts at temperatures above 160 °C. The sum of hesperidin and its HHP in the SW extracts was strongly correlated with antioxidant activities, whereas the contents of hesperetin and naringenin were strongly correlated with enzyme inhibitory activities. Hesperetin exhibited the highest antioxidant activities (2,2-diphenyl-1-picrylhydrazyl radical scavenging activity, ferric-reducing antioxidant power, and oxygen radical absorbance capacity), whereas hesperetin-7-O-glucoside exhibited the highest enzyme inhibitory activities (angiotensin-Іconverting enzyme (ACE) and pancreatic lipase (PL)). Naringenin exhibited the highest enzyme inhibitory activities (xanthine oxidase and α-glucosidase). PMFs (sinensetin, nobiletin, and tangeretin) also exhibited relatively high inhibitory activities against ACE and PL. This result confirms the potential of SW for extracting and hydrolyzing bioactive flavonoids from Citrus unshiu peel. In part 3, hesperidin was converted into hesperetin-7-O-glucoside and hesperetin with high biological activity in a semi-continuous mode. The optimum condition for maximum production of hesperetin-7-O-glucoside and hesperetin with minimal loss of hesperidin was temperature of 182.8 °C, and residence time of 3.2 min, where the predicted maximum yields of hesperetin-7-O-glucoside and hesperetin were 11,499.5 and 8,030.1 μg/g dry sample, respectively. Temperature was an important factor in SW hydrolysis of hesperidin. The effect of the residence time on hydrolysis was dependent on the temperature, where the short residence time was required at high temperature. This result confirmed the possibility of the conversion of hesperidin to valuable compounds with short time using an environmentally friendly solvent (water). 감귤 껍질에는 flavanone으로서 hesperidin과 narirutin이 다량 함유되어 있으며, polymethoxyflavones(PMFs)로서 sinensetin, nobiletin, tangeretin이 소량 함유되어 있 는데, 이들 성분은 항산화, 항염, 항암, 심장 보호 등의 기능성을 나타낸다. 제1부 에서는 아임계수를 이용하여 온주밀감 껍질로부터 플라보노이드를 여러 온도(120 −180 °C)와 유속(1.0−2.0 mL/min)에서 추출하여 추출기작을 밝혀내었다. Hesperidin, narirutin, PMFs의 추출수율은 120 °C에서 40.9%, 69.0%, 67.4%이었으 며, 추출온도를 160 °C로 증가시키면 79.6%, 81.9%, 89.0%로 증가하였으나, 추출 온도 180 °C에서는 열분해되어 감소하였다. 물의 유속 1.0−2.0 mL/min에서의 추 출 곡선을 thermodynamic partitioning과 kinetic desorption 모델에 적용하여 추출 기작을 예측하였다. 추출 속도는 추출 초기 단계에서는 빨랐지만 후기 단계에서 는 느렸다. Thermodynamic partitioning 모델은 추출 초기에는 추출속도를 잘 예측 할 수 있었으나 추출 후반부에는 잘 예측하지 못하였다. 반면 two-site kinetic desorption 모델은 추출 전반부 뿐만 아니라 후반부에서도 추출 속도를 매우 예측 할 수 있었으며, 이로부터 감귤 껍질로부터 플라보노이드의 추출은 주로 입자 내 확산에 의해 이루어진다는 것을 알 수 있었다. 또한 two-site kinetic desorption 모 델은 열분해되는 온도(180 °C)에서도 추출속도를 잘 예측할 수 있었던 것으로 보 아, 이 모델은 아임계수를 이용한 감귤 플라보노이드의 추출은 물론 분해 기작을 모두 잘 설명 할 수 있었다. Hesperidin의 확산계수는 120 °C, 1 mL/min에서보다 160 °C, 2 mL/min에서 약 9.8배 높았다. Hesperidin의 확산에 필요한 활성화 에너 지(37.2−43.8 kJ/mol)는 narirutin과 PMFs의 활성화 에너지(8.2−36.8 kJ/mol)보다 높았다. 따라서 감귤 껍질로부터 플라보노이드의 추출은 주로 입자 내 확산에 의 해 이루어졌으며, 환경 친화적인 용매인 물을 사용하여 단시간 내에 추출할 수 있음을 보여주었다. 제2부에서는 아임계수를 사용하여 감귤 껍질로부터 플라보노이드를 추출과 가 수분해하였고, 아임계수 추출물의 개별 플라보노이드의 수율, 항산화 활성 및 효 소 억제 활성을 측정하였다. Hesperidin과 narirutin의 추출수율은 추출온도가 145 °C에서 165 °C로 증가함에 따라 증가하였다. 제1배당체(hesperetin-7-O-glucoside, prunin), 비배당체(hesperetin, naringenin)와 같은 가수분해물은 160 °C 이상의 온도 에서 생성되었다. 아임계수 추출물에서 hesperidin, hesperetin-7-O-glucoside, hesperetin 함량은 항산화 활성과 밀접한 관련이 있는 반면, hesperetin과 naringenin 의 함량은 효소 억제 활성과 밀접한 관련이 있었다. Hesperetin은 가장 높은 항산 화 활성을 보인 반면, hesperetin-7-O-glucoside는 angiotensin-І converting enzyme(ACE)과 pancreatic lipase(PL)에 대한 강한 저해 활성을 나타내었다. Naringenin은 xanthine oxidase와 α-glucosidase에 대한 강한 저해 활성을 나타내었 다. PMFs도 ACE와 PL에 대해 상대적으로 높은 저해 활성을 나타내었다. 따라서 친환경 용매인 물을 이용하여 짧은 시간 내에 감귤 껍질로부터 생리횔성이 높은 플라보노이드를 추출 및 가수 분해할 수 있음을 확인하였다. 제3부에서는 감귤 미숙과 착즙박을 대상으로 반연속식 아임계수 추출 및 가수 분해 장치을 이용하여 아임계수 추출물 중의 hesperidin을 생리활성이 높은 hesperetin-7-O-glucoside와 hesperetin으로 가수분해하였다. Hesperidin의 손실을 최 소화하면서 동시에 hesperetin-7-O-glucoside와 hesperetin의 생성을 극대화하기 위한 최적조건은 가수분해 온도 182.8 °C와 체류시간 3.2분이었으며, 위 조건에서 hesperetin-7-O-glucoside와 hesperetin의 생성량은 각각 11,499와 8,030 μg/g dry sample이었다. 처리 온도는 hesperidin의 아임계수 가수분해에 있어서 가장 중요한 요소였다. 체류시간이 가수분해에 미치는 영향은 온도에 따라 달랐으며, 고온의 가수분해 조건에서는 짧은 체류 시간이 요구되었다. 따라서 환경 친화적 용매인 물을 사용하여 짧은 시간 내에 hesperidin을 기능성이 높은 물질로 연속적으로 전 환할 수 있는 가능성을 확인하였다.

Association of hepcidin with anemia parameters in incident dialysis patients : difference between dialysis modalities

임정훈 Kyungpook National University 2018 국내박사

목적: 만성 신부전에서 빈혈은 흔히 동반되지만 아직까지 철분대사나 조혈작용을 효과적으로 대변해주는 인자는 없는 상태이다. 혈청 헵시딘은 최근 철분 항상성과 관련된 주요 인자로 주목 받고 있으나 이와 관련된 인자들에 대한 연구는 부족한 상태이다. 본 연구에서는 투석을 처음 시작하는 말기신부전 환자들을 대상으로 혈청 헵시딘과 철분 지표들 및 다른 임상 지표들과의 관련성에 대해 분석하였다. 방법: 전향적 다기관 연구에 등록된 총 123명의 새로 투석을 시작한 환자들을 대상으로 연구를 진행하였으며 그 중 110명의 환자들이 연구를 완료하였다. 이 중 복막투석을 시행한 환자는 68명이었고 42명은 혈액투석을 시행하였다. 환자들은 6개월간 관찰되었으며 헵시딘 측정은 효소면역분석법으로 측정하였다. 헵시딘과 다른 임상 변수들과의 관계는 연구등록 시점과 투석 시작 후 6개월째에 선형 회귀모형을 통해 분석하였다. 결과: 혈청 헵시딘은 복막투석 환자군과 혈액투석 환자군 모두에서 6개월 후 증가하였다. 복막투석 환자군은 연구 기간 중 더 적은 양의 적혈구생성자극제를 사용하고도6개월의 투석 후 혈액투석군에 비해 높은 헤모글로빈을 보였다. 다변량 분석을 통해 각 연구 집단에서의 혈청 헵시딘 예측인자를 분석해보면 유지투석을 시행하기 전의 말기신부전 환자에서 혈청 헵시딘 예측인자는 aspartate aminotransferase (β=20.738, P=0.002), interleukin-6 (β=9.115, P=0.001), 페리틴 (β=0.042, P=0.041), 트랜스페린 포화도 (β=0.689, P=0.004), 인 (β=6.283, P=0.002) 이었고, 6개월간 복막투석을 시행한 환자들에서는 페리틴 (β=0.056, P<0.001), 총철결합능 TIBC (β=−0.184, P=0.023) 이었으며, 6개월간 혈액투석을 시행한 환자 집단에서는 페리틴 (β=0.048, P=0.095), 총철결합능 (β=−0.225, P=0.015), 소변량 (β=−0.021, P=0.004) 이었다. 결론: 혈청 헵시딘과 철분지표들과의 관계는 복막투석과 혈액투석 환자들에서 다르게 나타났다. 혈액투석을 처음 시작하는 말기 신부전 환자에서 소변량은 헵시딘의 독립된 예측인자로 밝혀졌다. 따라서 혈액투석을 시작하는 환자에서 잔여 소변량의 보존은 혈중 헵시딘을 낮출 것으로 생각된다.

Security analysis and quality of protection for wireless networks

임선희 Graduate School of Information Management and Secu 2010 국내박사

A diversity of wireless networks, with rapidly evolving wireless technology, are currently in service. Due to their innate physical layer vulnerability, wireless networks require enhanced security components. WLAN, WiBro, and UMTS have defined proper security components that meet standard security requirements. Extensive research has been conducted to enhance the security of individual wireless platforms, and we now have meaningful results at hand. However, with the advent of ubiquitous service, new horizontal platform service models with vertical cross-layer security are expected to be proposed. Research on synchronized security service and interoperability in a heterogeneous environment must be conducted. Security Interworking for Seamless Wireless Service - This thesis analyzes security mechanisms in wireless networks, and designs a secure and efficient protocol for a handover reusing the key materials generated before the handover phase. Especially, we describe in this thesis a handover scenario between WLAN and a WiBro network and propose a fast and efficient authentication scheme for the handover. In the scheme, a Serving Network (SN) plays a key distribution center role so that the Mobile Node (MN) can be quickly associated to a Target Network (TN) before starting a full authentication scheme where a remote Authentication Center (AC) is involved. In order to be sure that our handover protocol does not have any security flaws, we formally validated it using automatic protocol analyzer AVIPSA. Evaluation Model for Balanced Wireless Service - As wireless network cannot dispense with a proper security measure due to its inborn vulnerability, a new security measure has been developed with an advent of new wireless network technology. Each security measure properly serves the security needs of its associated wireless network as it was intended to. In heterogeneous environments, to design the balanced security components, quantitative evaluation model of security policy in wireless networks is required. Quality of Protection (QoP) estimates the stability of individual network system by quantifying security intensity. So, it can work as an evaluation standard for the security of network. Firstly, this thesis considers Historical Vulnerability Measure (HVM) and relative weight in total reward function for the improved QoP model. HVM is objectively organized by Flow-based Abnormal Traffic Detection Algorithm for utility function. Secondly, to design appropriate evaluation method of security policies in heterogeneous wireless networks, we formalize the security properties in wireless networks. As the benefit of security protocols is indicated by the QoP, we improve the QoP model and evaluate hybrid security policy in heterogeneous wireless networks by applying to the QoP model. Deriving relative indicators from the positive impact of security points, and using these indicators to quantify a total reward function, this thesis will help to assure the appropriate benchmark for combined security components in wireless networks.