호모토피 순환 A-무한대수, 잠재함수와 코호몰로지 이론

학위논문 (박사)-- 서울대학교 대학원 : 수리과학부, 2013. 2. 조철현.An A-infinity algebra has "associative up to homotopy" structure. For an A-infinity algebra $A$, we give a definition of strong homotopy inner products(if exist) which is the homotopy notion of cyclic inner products due to Kontsevich. From strong homotopy inner products we get several invariants which we call "potentials". We study their homotopy natures, gauge invariances etc. Also we find an explicit correspondence between cohomology elements of $A$ and isomorphism classes of strong homotopy inner products on $A$.Abstract 1. Introduction 2. Homotopy cyclic A-infinity algebra 2.1. A-infinity algebra 2.2. Homotopy equivalence of A-infinity algebras 2.3. A-infinity bimodules and inner products 3. Formal noncommutative geometry 3.1. Noncommutative function rings and vector fields 3.2. Noncommutative de Rham theory 3.3. Kontsevich-Soibelman's theorem 4. Review of cohomology theories on A-infinity algebras 4.1. Hochschild (co)homology for A-infinity algebras 4.2. (Negative) cyclic cohomology for A-infinity algebras 5. Potentials of homotopy cyclic A-infinity algebras and proof of Theorem A 5.1. Potentials 5.2. Theorem A 6. Proof of Theorem B 6.1. Correspondences between algebra and formal noncommutative geometry 6.2. Explicit relations 6.3. Construction of an automorphism 6.4. A connection to the Kontsevich-Soibelman's result 6.5. Gapped filtered cases 6.5.1. Filtered A-infinity algebras 6.5.2. Weakly filtered A-infinity bimodule homomorphisms 6.5.3. Formal manifolds 6.5.4. Darboux theorem 6.5.5. Corespondences 6.5.6. Theorem B in the filtered case 7. Proof of Theorem C Abstract(in Korean) Acknowledgement(in Korean)Docto

(A) STUDY ON THE IMPLEMENTATION OF DUE DILIGENCE AND ITS EFFECT : FOCUSSING ON THE MARINE HULL INSURANCE

A Study on the Implementation of Due Diligence and Its effect - Focussing on the Marine Hull Insurance - Marine Insurance is for the underwriter to indemnify the assured, in manner and to the extent there by agreed, against marine losses, that is to say, the losses incident to marine adventure. In marine hull insurance, a loss or damage to the assured's insured-against can be divided into two categories. The one is the losses which always can be covered from underwriters regardless of assured's due diligence to his insured-against such as the losses proximately caused by perils of the seas and Act of God, and the other is the losses which can be covered only if his due diligence have been proved. Accordingly, there may be some cases in which underwriters refuse to pay claims to the assured in case of his want of due diligence and actually, a lot of cases which an assured could not have been covered, existed through the history of marine hull insurance claims. Marine enterprisers such as ship's owners, managers, charterers and carriers should not overlook this kind of resonable care in running their business, and if they fail to do so, they might be in trouble with legal liability, to say nothing of their financial hardness and difficulty in management. Statistically, looking back the past marine accident cases in korea, the most parts of the accident are man-made disasters caused by want of due diligence. So, this study will focuss on this kind of marine losses and insurance clauses and other relevant rules containing due diligence such as due diligence of the assured in inchmaree clause, ITC-Hulls, 1983, and due diligence of carrier in Hague-Visby Rule and so on. This study also shows what the disadvantages to marine enterprisers are, caused by want of due diligence and the advantages of doing due diligence are. In conclusion, this study contends that marine enterprisers should perform due diligence in doing their business for both financial stability and good management of their companies. s

Unilateral Restless Legs Syndrome

하지불안증후군은 하지에 움직이고 싶은 충동이 있고 불편하거나 기분 나쁜 느낌이 동반되며, 이러한 충동이나 감각 증상이 쉬거나 앉거나 눕는 것처럼 활동이 적을 때 발생하거나 악화된다. 이러한 증상은 움직이면 부분적으로 혹은 완전하게 사라지며, 낮보다는 밤에 악화되거나 밤에만 나타나는 것을 특징이다. 하지불안증후군의 증상은 대개 양측 하지에서 비슷하게 나타나지만 전체 환자의 29%는 한쪽에서 증상이 더 심하게 나타난다. 하지만 지금까지 편측 하지에 증상이 국한된 경우는 세 건의 증례가 있었다.3 저자들은 하지불안증후군의 진단기준에 맞고, 이차적 원인이 없으며 편측 상하지에 국한된 특발하지불안 증후군의 증례를 경험하였기에 보고한다.OAIID:oai:osos.snu.ac.kr:snu2012-01/102/2014017262/14SEQ:14PERF_CD:SNU2012-01EVAL_ITEM_CD:102USER_ID:2014017262ADJUST_YN:YEMP_ID:A079623DEPT_CD:801CITE_RATE:0DEPT_NM:의학과SCOPUS_YN:NCONFIRM:

스티릴 염료와 보디피 스티릴 염료로 이뤄진 집중된 라이브러리를 통한 형광 프로브의 개발

학위논문 (박사)-- 서울대학교 대학원 : 자연과학대학 화학부, 2018. 2. 홍종인.Fluorescent probes based on small molecules are versatile tools for optical imaging and analytical sensing owing to their high sensitivity levels, fast response times, and simplicity. In addition, the development of a new probe is as important as its usefulness. Although many researchers have developed numerous fluorescent molecular probes, systematic probe development approaches are still lacking. An early conventional strategy for probe development is the target-oriented approach. Probes have been designed based on available empirical knowledge of molecular recognition mechanisms for individual targets. However, this strategy has serious limitations when studying unknown targets. Meanwhile, diversity-oriented fluorescent probe libraries with broad chemical diversity can be an alternative means of discovering new probes for targets that may not be accessible with known sensing moieties. Nevertheless, this strategy has a very low success rate despite the great investments in labor and time. As an alternative to both strategies, we considered focused fluorescent probe libraries that were designed to aid in the development of fluorescent probes based on an understanding of the target or target family. Sensing moieties of our probes were focused on the target family. Herein, we demonstrate the effectiveness of a focused library consisting of sensing moieties and styryl-based fluorescent dyes to provide selective probes for the detection of various targets. First, we prepared a focused fluorescent probe library for metal cations that was developed by combining metal cation ligand moieties and picolinium/quinolinium moieties as combinatorial blocks, which were connected through a styryl group. Selective probes for Hg2+, Ag+, and Zn2+ can be found in this library. Secondly, we constructed a focused probe library for phosphorylated biomolecules using metal complexes obtained from the previous library having a high binding affinity levels for metal cations. From the metal complexes, a selective probe for dTTP was developed. Thirdly, several of our styryl dyes from the previous library showed enhanced fluorescence in cells, and we found fluorescent nucleic acid probes. The feasibility of these probes was confirmed by cellular nucleic acid digestion experiments. Fourth, we developed a ratiometric fluorescent hydrogen peroxide probe, 1A. This probe was used to quantify glucose in diluted urine with enzyme-assisted glucose oxidation. Furthermore, we demonstrated that probe 1A could detect the activities of various oxidases as well as the presence and quantity of specific biomolecules by means of enzyme-assisted metabolism. Lastly, we developed a fluorescent imaging probe based on styryl BODIPY, v-BDP, for a mitochondria-targeting cancer therapy study. This was developed to deliver anticancer drugs to the mitochondria through triggering with intracellular esterase.Part 1. General introduction 1 1.1 Fluorescence and fluorophore 2 1.2 Fluorescence modulation 12 1.3 Development of molecular fluorescent probe strategy 21 1.4 References 25 Part 2. Development of fluorescent probes based on picolinium/ quinolinium based styryl dye from focused libraries 27 2.1 Introduction to styryl dye 27 2.2 Fluorescent metal cation probes 31 2.2.1 Introduction 31 2.2.2 Data & results 33 2.2.3 Experimental section 39 2.2.4 References 59 2.3 Fluorescent thymidine triphosphate probe 61 2.3.1 Introduction 61 2.3.2 Data & results 62 2.3.3 Experimental section 68 2.3.4 References 69 2.4 Fluorescent nucleic acid probes 71 2.4.1 Introduction 71 2.4.2 Data & results 72 2.4.3 Experimental section 79 2.4.4 References 83 2.5 Ratiometric fluorescent hydrogen peroxide probes 87 2.5.1 Introduction 87 2.5.2 Data & results 88 2.5.3 Experimental section 96 2.5.4 References 102 Part 3. Development of fluorescent mitochondria targeting imaging probes based on styryl BODIPY 106 3.1.1 Introduction to BODIPY 106 3.1.2 Introduction to cancer cells 110 3.2 Synthesis and photophysical properties of mono styryl BODIPY dyes 117 3.2.1 Introduction 117 3.2.2 Data & results 118 3.2.3 Experimental section 125 3.2.4 References 138 3.3 Mitochondria targeting cellular imaging probe based on picolinium styryl BODIPY for cancer treatment study 139 3.3.1 Introduction 139 3.3.2 Data & results 140 3.3.3 Experimental section 145 3.3.4 References 146 국문 초록 148Docto

Ship compartment modeling and naval architectural calculation based on a non-manifold polyhedron modeling kernel

학위논문(박사)--서울대학교 대학원 :조선해양공학과,2006.Docto

公共監査의 獨立性에 대한 硏究

학위논문(석사)--서울대학교 행정대학원 :행정학과 정책학전공,2003.Maste

Synergistic anti-tumor effect of ionizing radiation and β-lapachone on the human cancer cell line

의학과/박사[한글] β-lapachone (β-lap)은 남아메리카에 자생하는 lapacho란 나무의 껍질에서 추출하여 합성된 물질로 감염질환에서 악성종양까지 효과를 나타내는 다양한 약리작용을 가지고 있다. 특히 β-lap은 백혈병, 다발성골수종, 유방암, 전립선암 등 광범위한 사람암 세포주에 대해서 항암작용을 가지는 것으로 알려져 있다. β-lap은 자체로도 항암효과를 나타내지만 방사선이나 Taxol 같은 항암제와 병용하는 경우, 항암상승작용이 있는 것으로 알려져 있다. β-lap 자체로는 독성을 나타내지 않는 낮은 농도에서도 방사선을 병용하면 강력한 항암작용을 나타내는 것으로 알려져 있어, 방사선 민감제로써 활용가능성이 높은 약물이다. 본 연구의 목적은 다음과 같다. 1. β-lap과 이온화방사선의 항암상승효과를 in vitro, in vivo 실험을 통하여 검증하고자한다. 2.이온화방사선에 의해 유도되는 NAD(P)H:quinone oxidoreductase (NQO1)이 β-lap과 이온화방사선의 항암상승효과의 기전임을 증명하고자 한다. 3.암세포에서 NQO1의 발현 정도를 알아내면 β-lap과 이온화방사선의 항암상승효과를 예측할 수 있는지 알아보고자 한다. 이런 연구목적을 검증하기 위한 가설로는 “1. β-lap과 이온화방사선의 항암상승효과는 이온화방사선에 의해 유도되는 NQO1에 의해 β-lap 항암효과가 증진되기 때문이다. 2. NQO1 발현 정도를 치료 전 확인하면 β-lap과 이온화방사선의 항암상승효과를 예측할 수 있다”로 정하였다. 실험에 사용된 세포주로는 사람 대장암에서 기원한 RKO 세포주, 사람 폐암에서 기원한 A549 세포주, 사람 두경부종양에서 기원한 AMC-HN-1, -3, -4, -6, -9을 이용하였다. 실험에 사용된 약물로는 β-lap과 NQO1 억제자인 dicumarol을 구입하여 사용하였다. 세포생존율은 세포집락형성능법과 MTT assay을 이용하였고, NQO1, p53, p21, NF-kB의 발현은 western blot을 이용하여 확인하였다. β-lap과 방사선에 의해 유도되는 세포사멸을 관찰하기 위해서 DAPI 염색, DNA 분절 관찰법, Annexin V-PI 염색법을 이용하였고, 세포주기의 변화를 관찰하기 위하여 PI 염색 후 유세포 분석을 시행하였다. 방사선조사에 의한 NQO1의 발현 증가를 관찰하기 위하여 면역형광염색을 시행하였다. 세포집락형성능법으로 다양한 세포주에서 NQO1 발현 정도와 β-lap의 세포독성의 관계를 알아 보았다. 또한 β-lap과 방사선의 항암상승효과가 dicumarol에 의해 소멸되는지를 확인하였다. In vitro 실험 결과를 생체내에서 확인하기 위하여 누드 마우스를 이용하여 종양성장 지연을 관찰하였고, 마우스의 종양에서 채취한 조직을 냉동보관 후 TUNEL 염색을 시행하여 세포사멸을 관찰 하였다. 위의 실험결과를 요약하면 다음과 같다. 1. 5 mM b-lap과 6 Gy 이온화방사선 단독 처리시 각각 67%, 42%의 세포사가 있었으나 병용시 89%의 세포사가 있어, b-lap과 이온화방사선 간의 상승작용을 관찰할 수 있었고, 방사선조사 후 4시간 후에 b-lap을 투여하여도 동시 투여한 경우와 비슷한 결과를 보여, 그 기전은 b-lap이 DNA 손상복구를 억제하는 것이 아님을 알았다. 2. b-lap과 이온화방사선 병용 시 일차적으로 세포사멸이 일어나고 8시간 이후에는 세포괴사도 동시에 일어났다. 3. 방사선에 의해 유도되는 p53이나 NF-kB는 b-lap에 의해 억제되거나 파괴되었는데, p53의 발현은 방사선 단독처리 시 최고 2.8배 증가하였지만, b-lap 단독군이나 병용군에서는 오히려 50% 내외로 감소되었다. 4. 방사선에 의해 일어나는 G2기 세포주기 정지가 b-lap에 의해 억제되어 세포사가 항진되었다. 5. b-lap과 이온화방사선의 항암상승효과는 방사선에 의해 유도되는 NQO1의 발현에 기인하며, NQO1을 dicumarol로 억제할 경우 β-lap과 이온화방사선의 항암상승효과는 소실되었다. 6. b -lap에 의한 세포독성은 NQO1 발현 정도와 비례하는 양상을 보였는데, NQO1 발현이 비교적 높은 AMC-HN-6과 A549 세포주에서는 β-lap (5 mM) 처리 시 각각 84%, 87% 세포사가 발생하였다. 7. In vitro 실험에서 확인한 β-lap과 이온화방사선의 항암상승효과는 누드 마우스의 종양성장지연 이용한 in vivo 실험을 통해서도 확인할 수 있었다. 이상의 결과를 종합하여 다음과 같은 결론을 얻을 수 있었다. 첫째, β-lap과 이온화방사선의 항암상승효과는 NQO1 발현 정도와 비례하며, NQO1 발현 정도로 β-lap과 이온화방사선의 항암효과를 예측하는 것이 가능할 것으로 생각된다. 둘째, 방사선에 저항성을 가지는 종양도 방사선조사로 NQO1이 유도 발현되면, b-lap과 병용하여 효과적인 치료를 할 수 있을 것이다. [영문] β-lapachone (β-lap), a natural o-naphthoquinone, presents in the bark of the lapacho tree, it is cytotoxic against a variety of human cancer, including colon, prostate, promyelocytic leukemia, breast, and lung and potentiates the anti-tumor effect of Taxol. In addition, β-lap has been reported to radiosensitize cancer cells by inhibiting the repair of radiation-induced DNA damage with little toxicity β-lap alone. At lower doses, it is a radiosensitizer of a number of human cancer cell lines. However, the mechanism of cell death triggered by β-lap is unknown. Recently, new hypothesis suggested that β-lap triggers apoptosis in a number of human cancer cell lines through a unique apoptotic pathway that is dependent upon NQO1, a two-electron reductase. In the present study, we investigated the cytotoxicity of β-lap against human cells as well as the combined effect of β-lap and ionizing radiation for in vitro and in vivo studies. An incubation of RKO cells with 5 μM of β-lap for 4 h killed almost 90% of the clonogenic cells. An incubation of RKO cells with 5 μM of β-lap for 4 h or longer also caused massive cell death including apoptosis and necrosis. Unlike other cytotoxic agents, β-lap did not increase the expression of p53 and p21 and it suppressed the NF-κB expression. Radiation and β-lap acted synergistically in including clonogenic cell death and apoptosis in RKO cells when β-lap treatment was applied after but not before the radiation exposure of the cells. Interestingly, a 4 h treatment with 5 μM of β-lap starting 2, 4, 8 h after irradiation was as effective as that stating immediately after irradiation. The mechanisms of β-lap induced cell killing is controversial but a recent hypothesis is that β-lap is activated by NAPD(P)H: quinone-oxidoreductase (NQO1) in the cells followed by an elevation of cytoslic Ca2+ level and activation of proteases leading to apoptosis. It has been reported that NQO1 level in cells is markedly up-regulated at 4 h after irradiation and for longer than 24 h after irradiation. Indeed, using immunological staining of NQO1, we observed a significant elevation of NQO1 expression in RKO cells 4 h after 2.5 Gy irradiation. Such a prolonged elevation of NQO1 level after irradiation may be the reasons why the β-lap treatment applied 4 h after irradiation was as effective as that applied immediately after irradiation in killing the cells. In view of the fact that the repair of radiation-induced damage is usually completed within 1-2 h after irradiation, it is highly likely that the β-lap treatment applied 4 h after irradiation could not inhibit the repair of radiation-induced damage. NQO1 expression directly correlated with sensitivity to a 4-h pulse of β-lap in various cancer cell lines, and the NQO1 inhibitor, dicoumarol, significantly protected NQO1-expressing cells from all aspects of β-lap toxicity. NQO1 levels significantly correlated with β-lap sensitivity. Cell cycle analysis was performed on β-lap-treated cells using PI staining and flow cytometry. Although the result showed no apparent change in the cell cycle after β-lap treatment, the appearance of apoptotic cells (<2 N) was accompanied by the disappearance of G0/G1 cells. The increase of p21 by β-lap was not found in RKO human colon cancer cell lines. However, β-lap inhibited G2 check point by irradiation. For in vivo study, RKO cells were injected S.C. into the hind-leg of Nu/Nu mice, and allowed to grow to 130 mm2 tumor. The mice were i.p. injected with β-lap or saline 2 h after irradiation of tumors with 10 Gy of X-ray. The radiation induced growth delay was increased by 2.4 μg/g of β-lapachone. Taken together, we may conclude that the synergistic interaction of radiation and β-Lap in killing cancer cells is not due to radiosensitization by β-lap but to enhancement of β-lap cytotoxocity by radiation through up-regulation of NQO1. The fact that NQO1 is elevated in tumors and that radiation causes prolonged increase of the NQO1 expression may be exploited to preferentially kill tumor cells using β-lap in combination with radiotherapy. We expect that β-lap could work effectively as a radiosensitizer, even against the most radioresistant human cancer cell lines. Future studies on the nature of damage caused by NQO1-directed antitumor agents will be necessary to fully understand the complex relationship between NQO1 levels and ultimate toxicity. In summary, our results provide evidence that NQO1 is responsible for bioactivation of antitumor quinones in human tumor cells.ope

Efficacy and tolerability of tolterodine in children with neurogenic bladder

학위논문(석사)--서울대학교 대학원 :의학과 비뇨기과학전공,2005.Maste

Gene-centered Methodology and Molecular Biology

This paper investigates the role and the significance of genecentered methodology in molecular biology. I claim that methodological considerations has played an important role in the historical development of molecular biology and are likely to do the same in future molecular biology research. I also claim that there are certain limitations with regard to the usefulness of the genecentered methodology in molecular biology research. I discuss the views of Lewontin, Keller and Morange on this issue to argue my claims