(A) Study on the Fabrication of Planar Buried Heterostructure Laser Diode Using Meltback Method

A PBH-LD, a kind of strongly index guided laser, has been made by a meltback method by using a vertical LPE system which was made in our laboratory for ourselves. Formation of a mesa shape by a meltback method has an advantage in the reduction of damages on a substrate due to chemical etching and heating during regrowth. After the investigation of several characteristics of meltback solutions and meltback temperature, we confirmed that both of chemical etching and meltback method should be used to make a high performance PBH-LD. Therefore, we have formed mesa shapes successively with chemical etching and the meltback method. It is considered that the characteristics of the interface between the substrate and current blocking layers grown after the meltback may be excellent because of high meltback temperature of 610℃. The width of an active layer has been controlled to be 0.8 to 1.2㎛ so that the fabricated LD could operate with single mode in the lateral direction. To reduce the leakage current of current blocking layers, the widths of p-InP and n-InP layer have been grown to be 1.2㎛ and 1.6㎛, respectively. From the measurement of electric and optical characteristics of the fabricated MQW-PBH-LD, it was confirmed to be operated with low current and high performance. When the length of resonator was 300㎛, its characteristics were as follows: the threshold current of 10mA, the internal quantum efficiency of 82%, the internal loss of 9.2cm-1, and characteristic temperature of 65K. From the measurement of far-field pattern, we confirmed that it was operated with single mode in both directions parallel and normal to the junction interface. And we observed the variation of threshold current varying the leakage width at a certain cavity length and then applying the same widths to different cavity lengths and as a consequence, we clarified that the threshold current became low in the decrease of the leakage width and in the increase of the ratio of specific resistivity of leakage region to active region. We also made a comparison between the calculated threshold current in the absence of leakage region and the measured threshold current in the opposite case. As a result, the ratio of specific resistivity was about 0.5 in the measured LD, which has the width of a active layer of 1.4㎛ and leakage width of 0.6㎛

산화그래핀을 이용한 항바이러스 약물 스크리닝 플랫폼 및 생리활성 임플란트 소재 개발

학위논문(박사) -- 서울대학교대학원 : 자연과학대학 화학부, 2022.2. 민달희.Novel technologies to treat diseases, such as tissue engineering and drug discovery methodologies, have developed in conjunction with advances in civilization and science. However, certain problems in the field of life sciences have not received sufficient attention and remain unresolved. A classic example is the discovery of therapeutic agents for viral infections. In the globalized modern society, it is imperative to protect and treat humanity from viral infections. However, due to the diversity of viruses and the rapid emergence of mutations, it is impossible to respond immediately using the current drug development processes. Therefore, the development of a new drug discovery method is necessary to overcome this problem and allow the quick discovery of antiviral drugs. Another example is the unmet need to increase the bioactivity of implant materials. Although biocompatibility is essential to prevent adverse effects following the implantation of external materials into the body, bioactivity, which described interactions between the prosthetic material and biological components, is more critical in securing the long-term stability of prosthetic materials. Thus, many studies are being conducted to increase bioactivity by controlling the surface properties of the implant material in various ways. Nevertheless, compared to minutely controlling the thickness and roughness of its oxide film, there is a continuing need for a modification method that is somewhat simpler. Nanobiotechnology refers to the combination of nanotechnology, which involves the development of new materials by identifying their physical properties at the atomic or molecular level, and biotechnology, which refers to the study of life phenomena. Nanobiotechnology can be applied to solve biological and biotechnological problems unsolvable by classical approaches. Therefore, the core goal of nanobiotechnology is to develop new nanomaterials with excellent properties that can be applied to various fields such as biosensors, biochips, drug delivery, therapeutics, and tissue regeneration. Graphene oxide (GO) is an attractive nanomaterial due to its excellent physicochemical properties, originating from its oxygen functional groups and sp2 carbon domains. As a representative feature, GO can quench fluorescent molecules located within 20 nm by adsorption. Therefore, GO is being used in research on various fluorescence-based biosensors. In addition, because GO has excellent biocompatibility and bioactivity to induce bone regeneration and cell differentiation, it is being used in regenerative medicine and prosthetic research. Herein, we suggest a solution to the problems mentioned above using GO. First, we will address the development of a drug screening platform for rapid antiviral drug discovery: We developed a graphene oxide-based RNA viral helicase assay named RheGO. This assay could be used to analyze helicase activity in real-time with excellent reproducibility and reliability, and was applicable to antiviral drug screening. The antiviral activity of the hit compound identified with RheGO was also confirmed in vitro and in vivo. Second, we will address the need to improve the bioactivity of implant materials: We coated GO on the surface of the implant material with simple processing. As a result, we confirmed that the adhesion and proliferation of gingival fibroblasts increased when GO was coated. Moreover, we confirmed that the expression of focal adhesion genes was increased when gingival fibroblasts came into contact with GO. Thus, we showed that problems that were difficult to solve with classical methods could be solved with new approaches using nanobiotechnology. Moreover, we believe that many medical and biotechnology problems can potentially be solved using GO to develop new methods for antiviral drug discovery and new materials with excellent bioactivity.문명과 과학기술이 발전하면서 질병을 치료하기 위한 약물의 발굴 방법과 조직공학 기술 또한 함께 발전하였다. 그러나 생명과학 분야에서 상대적으로 주목받지 못하여 아직도 해결되지 않은 문제들이 존재하고 있다. 대표적인 예로서 바이러스 감염 질환 치료제 발굴을 들 수 있다. 세계화된 현대 사회에서 바이러스 감염으로부터 인류를 보호하고 치료하는 것이 얼마나 중요한지는 이루 말할 수 없다. 그러나 바이러스의 다양성과 빠른 변이의 출현으로 인해 기존의 약물 개발과정으로는 신속한 대응이 불가능하다는 한계가 있다. 따라서 이를 극복하기 위한 새로운 약물 발굴방법 개발과 이를 이용한 신속한 항바이러스 약물 발굴을 해야 한다. 또 다른 예로서, 임플란트 물질의 생리활성을 높이는 것이다. 외부 물질을 생체 내로 삽입할 때 생체내 부정적인 영향이 나타나지 않도록 하는 생체 적합도는 필수적이지만, 인공삽입술에서 인공삽입물질과 생체분자및 세포들 간의 강력한 상호작용을 할 수 있도록 생리활성을 높이는 것은 인공삽입물질의 장기간 안정성을 확보할 수 있다는 점에서 더욱 중요한 의미를 갖는다. 비록 인공삽입물로 활용될 수 있는 물질 종류가 다양하지 않지만, 그럼에도 불구하고 물질의 표면 특성을 여러가지 방법으로 조절하여 생리활성을 높이는 연구들이 수행되고 있다. 그러나 물질 표면의 산화막 두께 및 거칠기를 조절하는 섬세한 방법에 비해 다소 간편한 개질 방법에 대한 요구가 지속되고 있다. 나노바이오기술은 원자나 분자 단위에서의 물성을 규명하여 새로운 물질을 개발하는 나노기술과 이를 이용하여 인간의 질병 및 생명현상을 연구하는 바이오기술이 결합된 것으로서, 고전적인 접근 방법으로 해결하지 못한 생물학 및 생명공학적 문제를 해결할 수 있는 기술이다. 그렇기 때문에 새로운 나노물질을 개발하고 뛰어난 물성을 갖는 나노물질을 바이오센서, 바이오칩, 약물전달, 치료제, 조직재생과 같은 다양한 분야에 적용시키는 것이 나노바이오기술의 핵심이라 할 수 있다. 특히, 다양한 나노물질 중에서 산화그래핀은 산소 작용기와 그래핀 도메인을 가지고 있으며 이로 인해 뛰어난 물리화학적 특징을 보이는 매력적인 나노물질이다. 대표적인 특징으로서, 산화그래핀은 표면에 흡착되거나 20 nm 내에 위치한 형광물질을 소광 시킬 수 있다. 이를 기반으로 다양한 형광 기반 바이오센서연구에 산화그래핀이 활용되고 있다. 또한 산화그래핀은 뛰어난 생체적합성과 뼈 재생 및 세포 분화를 유도할 수 있는 생리활성 특징을 가지고 있다. 이와 같은 특징으로 인해, 재생의학 및 인공삽입물 연구에 산화그래핀이 쓰이고 있다. 본 논문에서 우리는 산화그래핀을 이용하여 앞서 언급한 두 가지 문제에 대한 해결방법을 제시하고자 한다. 첫째, 신속한 항바이러스 약물 발굴을 위한 약물 스크리닝 플랫폼 기술 개발: 우리는 산화그래핀 기반의 RNA 바이러스성 헬리케이즈 활성 분석 기술인 RheGO를 개발하였다. 형광이 개질된 핵산 기질을 사용하여 실시간으로 핼리케이즈의 활성을 확인할 수 있는 본 분석 기술은 뛰어난 재현성과 신뢰성을 보여주었고, 항바이러스 약물 스크리닝에 적용이 가능함을 보였다. 그리고 발굴된 약물 후보군의 세포 수준 및 동물모델 수준에서 유의미한 항바이러스 효과를 확인하였다. 둘째, 임플란트 물질의 생리활성도 향상: 우리는 산화그래핀을 임플란트 물질 표면에 부착하여 그 영향을 확인하였다. 연구 결과 우리는 임플란트 물질에 산화그래핀을 코팅하면 치은섬유아세포의 부착 및 증식이 증가함을 확인하였다. 그리고 이는 치은섬유아세포가 산화그래핀과 접촉할 때 초점접착 유전자의 발현이 증가되어 나타난 결과임을 확인하였다. 본 연구 결과에서 우리는 고전적인 방법으로 해결하기 어려운 문제를 나노바이오기술을 이용한 새로운 접근법으로 해결할 수 있음을 보여주었다. 따라서 우리는 나노 물질인 산화그래핀을 활용하여 항바이러스 약물 발굴을 위한 새로운 방법 개발 및 조직공학을 위한 생리활성이 뛰어난 새로운 물질을 개발함으로써, 향후 많은 의료 및 생명공학 문제들을 해결할 수 있을 것으로 기대한다.Abstract Table of Contents List of Figures Chapter 1. Introduction 1 1.1 Graphene Oxide: its Applications as Biosensor and Bioactive material 1 1.2 Description of Research 4 1.2.1 Identification of a Direct-acting Antiviral Agent Targeting RNA Helicase via a Graphene Oxide Nanobiosensor 4 1.2.2 Graphene Oxide-treated Surface on Pure Titanium Implant Materials Promotes Adhesion and Proliferation of Human Gingival Fibroblast 6 1.3 References 7 Chapter 2. Identification of a Direct-acting Antiviral Agent Targeting RNA Helicase via a Graphene Oxide Nanobiosensor 11 2.1 Introduction 11 2.2 Results 15 2.3 Conclusion 37 2.4 Materials and Methods 38 2.5 References 50 Chapter 3. Graphene Oxide-treated Surface of Pure Titanium Promotes Adhesion and Proliferation of Human Gingival Fibroblast 57 3.1 Introduction 57 3.2 Results 59 3.3 Conclusion 71 3.4 Materials and Methods 72 3.5 References 78 Chapter 4. Conclusion 80 Summary in Korean (국문 요약) 82 Acknowledgement 85 Curriculum Vitae 87박

The Influence of Food Ingestion and Sample Storage on Direct LDL-Cholesterol Measurement by Immunoseparation Method

Background : Elevated level of low density lipoprotein-cholesterol (LDL-C) is one of the major risk factors for the development of coronary heart disease. Direct LDL-C determination method by immunoseparation (DLDL-C) recently developed is claimed not to be influenced by food ingestion. We re-evaluated the effects of diet and storage conditions for this method. Methods : Samples were collected from thirty-two medical college students before and after meal to study the effects of diet on this method. We compared the difference of LDL-C of filtered samples between refrigerated and frozen state. We also compared direct and indirect calculated measurements of LDL-C with ultracentrifugal beta-quantification (BQLDL-C) method. Results : Morning 2-hour-postprandial specimen can be acceptable with no minimal significant bias, but afternoon 2-hour or 4-hour-postprandial specimen cannot be recommended due to significant negative bias (8.6-9.6%). Storage of filtered samples showed no significant difference between frozen and refrigerated state. Calculated LDL-C when triglyceride level is more than 400 mg/dL was not reliable due to large proportional and constant bias. In contrast, DLDL-C showed good accuracy comparing with BQLDL-C (y=0.909x＋3.3, r=0.869, n=9, x=BQLDL-C, y=DLDL-C). Conclusions : In conclusion, morning two-hour postprandial specimens can be acceptable for DLDL-C, but afternoon postprandial specimens may not be recommended due to significant negative bias. DLDL-C seems to be reliable and useful especially for hypertriglyceridemic patients or follow-up cases of hypercholesterolemia with normal triglyceride or HDL-C levels.ope

살기좋은 우리동네 만들기(Improvement of residential community)

노트 : 제 4차 국토종합계획수립연구(주거부문) 이 책은 국토연구원의 자체 연구물로서 정부의 정책이나 견해와는 상관없음을 밝혀둡니다

Prevalence and Risks of Depression and Substance Use Among Adults Living with HIV in the Asia-Pacific Region

ope

The Effect of Red Pepper and Capsaicin on Gastric Emptying

Background/Aims: Capsaicin stimulates the release of several neuropeptides and has diverse effects on gastrointestinal function. We investigated the effect of intragastric red pepper or capsaicin on the gastric emptying in human. Methods: Fourteen healthy male volunteers were recruited. Gastric emptying was assessed by radio-opaque markers (ROMs) method and plasma acetaminophen (AAP) levels. Results: The clearance of ROMs at 2 hours and 3 hours was 10.6 ±15.9 and 73.1 ±34.6% after administration of placebo, 17.6 ±26.0 and 78.7 ±40.2% after administration of red pepper 3 g 27.8 ±34.0 and 73.2 ±31.9% after administration of red pepper 6 g, 2.1 ±5.1 and 15.5 ±20.7% afte administration of capsaicin 17.3 mg. Capsaicin significantly delayed the gastric emptying of ROMs The serum AAP concentrations were measured at 30, 45, 60, 75 and 90 min after administration o placebo (4.09 ±3.45, 8.09 ±4.13, 13.55 ±4.90, 15.50 ±3.44 and 13.0 ±7.53 μg/ml), red pepper 3 g (5.63 ±4.84, 8.88 ±4.76, 14.25 ±5.01, 15.11 ±5.16 and 16.80 ±6.57 μg/ml), red pepper 6 g (7.0 ± 7.19, 8.09 ±5.63, 12.09 ±6.04, 13.73 ±4.65 and 14.28 ±3.77 μg/ml), capsaicin 17.3 mg (4.50 ±2.88 , 7.17 ±3.19, 11.50 ±4.76, 11.17 ±3.71 and 13.33 ±3.72 μg/ml). Intragastric red pepper or capsaicin made no significant difference of serum acetaminophen level from placebo. Conclusions: Intragastric administration of capsaicin delayed gastric emptying of indigestible solid meal, whereas red pepper did not. The gastric emptying of liquid meal was affected by neither capsaicin nor red pepper.ope

Annual Report on the External Quality Assessment of Therapeutic Drug Monitoring and Testing for Drugs of Abuse in Korea (2013)

We performed two trials on the external quality assessment for therapeutic drug monitoring (TDM) and testing for drugs of abuse (DOA) organized by the Therapeutic Drug Monitoring (TDM) subcommittee of the Korean Association of Quality Assurance for Clinical Laboratories (KAQACL) in 2013. In each trial, two levels of control material for TDM, and positive and negative control material for DOA testing, were requested from candidate institutions. The number of participating laboratories was 106 and 105 for the first and second trials, respectively. The average number of drug items was 5.6 per institution. The most commonly tested substances were valproic acid, followed by digoxin, phenytoin, carbamazepine, and tacrolimus, in descending order. The mean inter-laboratory coefficients of variation for low- and high-level control materials were 9.3% and 6.7%, respectively. The most widely used TDM analysers were Architect i System (Abbott Diagnostics, USA), followed by Cobas Integra (Roche Diagnostics, Switzerland) and Cobas c501 analyser (Roche Diagnostics). The number of participating laboratories for DOA testing increased by 30% compared with that in 2012. We received 100% and 98.2% correct answers from the participating DOA laboratories in each trial, respectively. In the external quality assessment for TDM by the TDM subcommittee of KAQACL in 2013, the overall performance of TDM was similar to previous years and the inter-laboratory precision was improved compared with that in 2012. Continuous quality improvement for TDM testing is needed through participation in a proficiency-testing program.ope

Annual Report on the External Quality Assessment Scheme for Therapeutic Drug Monitoring and Testing for Drugs of Abuse in Korea (2014)

As the Therapeutic Drug Monitoring Subcommittee (TDMS) of the Korean Association of Quality Assurance for Clinical Laboratories (KAQACL), we organised two trials as an external quality assessment of therapeutic drug monitoring (TDM) and testing for drugs of abuse (DOA) in 2014. In each trial, low and high level control materials for TDM testing, and positive and negative control materials for DOA testing, were requested from institutions. The number of participating laboratories was 107 for the first trial and 106 for the second. The average number of drug items provided was 5.7 per institution. The most commonly tested substances were, in descending order, valproic acid, digoxin, tacrolimus, phenytoin, and vancomycin. The mean inter-laboratory coefficients of variation for low- and highlevel TDM control materials were 8.5% and 7.2%, respectively. The most widely used TDM analysers were the Architect i System (Abbott Diagnostics, USA), followed by the Cobas Integra (Roche Diagnostics, Switzerland) and the Cobas c501 analyser (Roche Diagnostics). The number of participating laboratories for DOA testing was 23% higher that than in 2013. In 96.9% of cases, our analysis confirmed the suitability of the tests at participating DOA laboratories in both trials. In the external quality assessment of TDM by the TDMS of KAQACL in 2014, the overall performance of TDM testing was found to be similar to that observed in the previous years, and inter-laboratory precision was higher than that in 2013. Continuous quality improvement of TDM testing by participation in a proficiency-testing program is necessary.ope

Effect of Accreditation on Accuracy of Diagnostic Tests in Medical Laboratories

BACKGROUND: Medical laboratories play a central role in health care. Many laboratories are taking a more focused and stringent approach to quality system management. In Korea, laboratory standardization efforts undertaken by the Korean Laboratory Accreditation Program (KLAP) and the Korean External Quality Assessment Scheme (KEQAS) may have facilitated an improvement in laboratory performance, but there are no fundamental studies demonstrating that laboratory standardization is effective. We analyzed the results of the KEQAS to identify significant differences between laboratories with or without KLAP and to determine the impact of laboratory standardization on the accuracy of diagnostic tests. METHODS: We analyzed KEQAS participant data on clinical chemistry tests such as albumin, ALT, AST, and glucose from 2010 to 2013. As a statistical parameter to assess performance bias between laboratories, we compared 4-yr variance index score (VIS) between the two groups with or without KLAP. RESULTS: Compared with the group without KLAP, the group with KLAP exhibited significantly lower geometric means of 4-yr VIS for all clinical chemistry tests (P<0.0001); this difference justified a high level of confidence in standardized services provided by accredited laboratories. Confidence intervals for the mean of each test in the two groups (accredited and non-accredited) did not overlap, suggesting that the means of the groups are significantly different. CONCLUSIONS: These results confirmed that practice standardization is strongly associated with the accuracy of test results. Our study emphasizes the necessity of establishing a system for standardization of diagnostic testing.ope

Annual Report on External Quality Assessment in Inborn Error of Metabolism in Korea (2001)

The trial of external quality assessment for inborn error of metabolism was performed in 2001. Total 5 specimens for neonatal screening tests were distributed to 68 laboratories with a response rate of 64.7% (44/68). All the control materials were sent as filter paper forms. Each laboratory replied the test results as the screening items they were testing routinely at the reception of the specimen among PKU screening, neonatal TSH, neonatal T4 (total/free), galactosemia screen, homocytinuria screen and histidinemia screen. The mean, SD, CV, median and range were analyzed.ope