Regeneration of Nicotinamide Coenzyme by Rhodium Complexes; Efficient Regeneration Methods and Applications

Dharmalingam Sivanesan 국민대학교 일반대학원 2014 국내박사

Abstract Regeneration of Nicotinamide Coenzyme by Rhodium Complexes; Efficient Regeneration Methods and Applications by Dharmalingam Sivanesan Department of Bio and Nano Chemistry Graduate School of Kookmin University Seoul, Korea Chapter 1. Overview on Available Regeneration Methods for Nicotinamide Coenzymes and Our Efforts for NADH Regeneration NADH-dependent or oxidoreductases mediated asymmetric synthesis are of particular interest because they are utilized in the synthesis of various pharmaceutically active intermediates. Hence regeneration of NADH coenzyme plays very important role in the biocatalysis. In this chapter we have summarized the previously available compounds and methods for the coenzyme regeneration. Also, based on the results available in the literature, our efforts toward making efficient regeneration method for coenzyme is rationalized based on the regeneration mechanism. Chapter 2. Effect of the Substituents in the 2,2’-Bipyridine Ligands of [Cp*Rh(bpy]Cl]Cl for Regeneration of NADH by Chemical and Indirect Electrochemical Methods The Rh(III) complexes having functionalized bpy ligands were synthesized and fully characterized. The hydrido complex [η5-Cp*Rh(bpyCH2OH)H]+, which could be generated either electrochemically by cathodic reduction of the [η5-Cp*Rh(bpy-CH2OH)Cl]Cl complex at −771 mV (versus Ag/AgCl) or chemically with formate, transformed NAD+ efficiently into NADH. The 5,5’-bpyCH2OH and 4,4’-bpyCH2OH ligated rhodium complexes were successfully generated the NADH by chemical and indirect electrochemical methods. The maximum activity was obtained for [η5-Cp*Rh(4,4’-bpyCH2OH) Cl]Cl (710 h-1) and [η5-Cp*Rh(5,5’-bpyCH2OH)Cl]Cl (1106 h-1) at 60°C chemically with formate anion. Although, the electron releasing groups are in 4,4’-position of 2,2’-pypyridine, the catalytic efficiency was decreased for linkable functional groups containing [Cp*Rh(bpy)Cl]+ complexes due to the functional groups interaction with metal center. Chapter 3. Water-soluble Carbene-containing Rhodium Complexes for Regeneration of NADH with Elevated Catalytic Turnover Frequency The Rh(III) complexes ligated with pyridyl-carbene ligands that can allocate high electron density on metal site was synthesized and fully characterized. The Rh(III) complexes effciently could regnerate the NADH by chemically with formate. Also, electrochemically by cathodic reduction of the [(η5-Cp*)Rh(4-t-butylpyridyl(NHC))Cl]Cl(7) complex at −980 mV vs. Ag/AgCl transformed NAD+ efficiently into NADH. In pH 9.2, the complex 7 shown the highest activity with a TOF = 6960 h-1 at 60°C. Here the catalytic activity was rationized based on the reduction potential of the catalysts 7, 8 and 9, and pH of the reaction medium. In the chemical regeneration, high concentration of NAD+ in the catalytic medium changes the pH to acidic which prohibit the formation of active intermidiate, [(η5-Cp*)Rh(4-t-butylpyridyl(NHC))H]+. Chapter 4. Efficient Regeneration of Coenzyme Using Dihydrogen and Combined studies with Lactate Dehydrogenase Enzyme We have demonstrated that the Rh(III) complexes [η5-Cp*Rh(bpy-OH)Cl]Cl and [(η5-Cp*)Rh(4-t-butylpyridyl(NHC))Cl]Cl having ligands dihydroxyl-bpy and N-heterocyclic carbene provide efficient regeneration of NADH using H2 gas. The highly active complexes were 3 and 4, and the generated NADH by 3 was utilized for the enantioselective synthesis of D-lactate with D-LDH. At pH 8.2 maximum turn over number 145 was obtained for D-lactate using 3. We believe that this system is suitable for the in-situ generation of NADH and enzymatic reductions because of the NADH regeneration without producing the environmentally harmful byproducts. Chapter 5. Covalently Attached Ru and Rh Bimetal Complexes for Photochemical Regeneration of NADH and Photoenzymatic Studies Utilization of solar energy as a sustainable and environmentally acceptable energy source has most attention due to the high abundance, cheap and clean energy. In this chapter we have described covalently attached bi-metal complexes 1 and 2 for the photochemical regeneration of NADH and the generated NADH was combined for enantioselective synthesis of D-lactate using NADH-dependent enzyme, D-LDH. In 1 and 2, mediator and photosensitizer were covalently attached through saturated and unsaturated covalent bonds. Among them 2 is shown the maximum generation of D-lactate from photoenzymatic method and it results from the higher electron density on the metal. Additionally, the conjugation properties of the 1 and 2 affect the electron transfer which decides the photochemical generation of NADH.

Lineage Restriction, Cellular Heterogeneity, and Patterning during Mammalian Digit Tip Regeneration

Johnson, Gemma Lee Harvard University ProQuest Dissertations & Theses 2022 해외박사(DDOD)

Regeneration can be broadly defined as the renewal of biological structures. This occurs over the lifetimes of all multicellular organisms as structures like epithelia are replaced by cell division and growth. Some vertebrates, however, are capable of regenerating entire appendages, such as limbs, after amputation. This type of regeneration goes beyond the maintenance of tissues and requires re-growth of entire appendages. One striking example is the axolotl, which can regenerate lost limbs and tails, among other complex tissues. Regenerative ability is more restricted within mammals, but mice and human children have the innate ability to regenerate digit tips. The digit tip is an anatomical structure that includes bone, connective tissue, nerves, blood vessels, the nail, and the nail epithelium. After amputation there is first a wound healing response that leads to closure of the wound epithelium. The blastema, a heterogeneous mass of proliferating cells, then forms and regenerates the non-epithelial structures of the digit tip. Mouse digit tip regeneration provides a model to study regeneration in mammals to determine principles of regeneration that will lead to advances in regenerative medicine in humans. This dissertation addresses two aspects of digit tip regeneration that advance our understanding of the mouse digit tip blastema: what is the cellular composition of the blastema, and does patterning of the blastema require the same genes that pattern the limb bud during embryonic limb development. Classically, the blastema has been described simply as a collection of proliferating cells. In the mouse digit tip, the blastema is made up of heterogeneous and broadly lineage restricted cells, but the full extent of heterogeneity is unknown. In Chapter 2 we use single-cell RNA-sequencing to define the cell types present in the unamputated and regenerating digit tip. We find that the blastema is largely made up of heterogeneous fibroblast populations with distinct gene expression programs. Other cell types such as immune cells, Schwann cells, osteoblasts, vascular cells, and more are also found in the blastema, some of which have been described before using histology. These broad cell types are also present in the unamputated digit tip. A computational lineage trajectory of the vascular, monocytic, and fibroblast populations confirms broad lineage restriction in the mouse digit tip blastema but suggests that subtler trans differentiation relationships may exist. We also find that certain fibroblast clusters expand during regeneration and express regeneration specific genes such as Mest. Patterning during limb regeneration has long been thought to be mediated by the same genes that pattern developing limbs. In Chapter 3 we explore the patterning of the mouse digit tip blastema in the dorsal-ventral axis using the well-known set of transcription factors that define the dorsal-ventral axis during limb development, En1 and Lmx1b. We show that En1 and Lmx1b are expressed during regeneration but not with dorsal-ventral polarity. Further, we develop a computational method to show that loss of En1 or Lmx1b does not perturb the dorsal-ventral morphology of the regenerated digit tip bone, indicating that the limb development dorsal-ventral patterning genes are not re-used during digit tip regeneration. Together, these chapters advance our knowledge of the digit tip blastema and provide a wealth of data and methods that can be used to further investigate the mechanisms of regeneration in a mammalian system.

객관주의적 인식론이 기독교학교교육에 미친 영향에 대한 비판적 연구 : “중생”에 대한 이해의 관점에서

김병재 아세아연합신학대학교 교육대학원 2018 국내석사

ABSTRACT A critical on the influence of Objectivism epistemology in Christian school -based on understanding “Regeneration”- Kim, Byoung Jae Master of Education The Graduate School of Education, Asia United Theological University The aim of this study is to suggest alternatives to objectivism epistemology in Christian educational view. Especially, This researcher suggests ‘regeneration’ among the Christian doctrines as an alternative. Therefore, this researcher studies ‘regeneration’ with the following questions. First, What is objectivism and what are the critical points about objectivism? Second, What is the influence of objectivism epistemology on education? Third, What is regeneration and what is epistemology based on regeneration? Fourth, how does epistemology based on regeneration restores Christian school education? This dissertation consists of five chapters. In the first chapter, the demands and significance of the study are demonstrated. In chapter Ⅱ, the effects of objectivism epistemology on education are discussed. And the objectivism epistemology is criticized from theories of Hans-Georg Gadamer, Karl R. Popper, Tomas S. Kuhn, and Michael Polanyi. Then in chapter Ⅲ, regeneration that core of Christian educational epistemology is explained with the three following points: surveying regeneration in the frame of salvation, examining the change of humanity’s will through regeneration in books of Jonathan Edwards, and presenting Christian epistemology based on regeneration in the light of Van Til. In chapter Ⅳ, The knowledge in objectivism epistemology is criticized on the basis of the epistemology based on regeneration, focussing on ‘non-independence’, ‘value orientation’, and ‘personality’. Also, This dissertation, on the basis of the epistemology based on regeneration, suggests what should be recovered in Christian school education, and this suggestion categorizes into areas: salvation, class, and practice. Finally, in chapter V, this researcher examines the importance of epistemology based on regeneration as a matter of Christian school education. Christian school cannot exist without the Truth of Christianity. To say specifically, regeneration is both the idea and practice, encompassing human knowledge, will, and practice. Therefore, In the following, this dissertation demonstrates that Christian school education should take as it is foundation epistemology based on regeneration. It will not only help to teach the proper knowledge in a Christian school but also restore the method of Christian school education and even students’ life. I hope that it is succeeding researches to be more theological, more detailed themes on Christian educational view.

Urban Regeneration Studies in Beijing Sub-Center Based on Public Policy-oriented

Bo DENG 서울시립대학교 국제도시과학대학원 2022 국내석사

도시재생은 도시에 필요한 일종의 재건 사업이다. 베이징 부도심의 도시화가 가속화됨에 따라 도시재생은 도시 건설 및 개발에 있어서 더욱 중요한 역할을 하고 있다. 많은 이해관계자(정부, 시장, 대중)가 참여하는 공공정책은 도시재생사업에서 무시할 수 없는 중요한 측면이다. 정부와 시장, 대중 그리고 기타 이해관계자 모두 도시재생사업에 핵심적인 역할을 할 것이다. 이해관계자의 성숙한 역할을 필요로 하는 도시재생 공공정책 개발에 있어서 한국이 중국보다 앞서 있다는 점을 감안하면 중국, 특히 베이징 부도심에서 도시재생 공공정책을 수립하는 데 있어 한국의 정책은 고려할 만한 가치가 있을 것이다. 본 연구는 베이징 부도심의 대표적인 도시재생사업(행정구역, 디자인 타운, 사우스 스트리트)을 모두 종합한 결과를 토대로 인터뷰와 설문지에서 얻은 데이터를 분석하여 베이징 부도심 도시재생의 특성 및 문제를 파악하고, 한국 도시의 사례를 충분히 학습하여 베이징 부도심의 도시재생 공공정책을 개선할 수 있는 몇 가지 제안을 내놓았다. 제안에는 도시재생의 법적인 제도를 개선하고, 도시재생 관리 플랫폼을 구축하여 더 많은 지원정책을 수립하고, 시장이 질서 있게 도시재생에 참여할 수 있도록 돕고, 대중이 도시재생활동에 적극적으로 참여할 수 있도록 지원해야 한다는 점을 포함한다. Urban regeneration is some kind of necessary reconstruction activity in the city. With the acceleration of urbanization of Beijing Sub Center, urban regeneration is playing a more and more important role in the construction and development of the city. In the urban regeneration projects, public policies involving many stakeholders (government, market, public, etc.) are important aspects that cannot be ignored. The government, the market, the public and other stakeholders will all play key roles in urban regeneration. Considering that South Korea, as a developed country, ahead of China in the development of urban regeneration public policy, whose role of stakeholders is more mature, it should be of great value to the formulation of urban regeneration public policy in China, especially in Beijing Sub Center. On the basis of fully combing the typical urban regeneration projects of Beijing Sub Center (Administrative Zone, Design town and South Street), this study analyzes the data from interviews and questionnaires, finds out the characteristics and problems of urban regeneration of Beijing Sub Center, by fully learning from the experience of Korean cities, gives some suggestions to improve the public policy of urban regeneration of Beijing Sub Center, Including: improving the law system of urban regeneration, establishing the urban regeneration management platform, formulating more supporting policies, helping the market to participate in urban regeneration orderly, and supporting the public to participate in urban regeneration actively.

Effects of Pinus densiflora needle extract on liver regeneration induced by partial hepatectomy in rat

이경석 Soonchunhyang University 2017 국내석사

Pine (Pinus densiflora) is widely distributed in Eastern Asia including Korea, China, Japan and Russia. The leaf (pine needle) has been used as a traditional medicine for gastroenteritis, hypertension, etc. Recently it has been reported that pine needle has anti-oxidative, anti-inflammatory, anti-tumor and anti-bacterial activities. The liver is an essential organ in animal since it plays a crucial role in protein synthesis, detoxification, regulation of glucose and other many metabolism. The liver has unique ability to regenerate potential after injury. Regenerative potential of the liver is well known and is widely used in physiological researches. Liver regeneration could be induced by partial hepatectomy (PH). After PH, liver regenerates via compensatory growth which does not means anatomic true-regeneration. The expanding liver does not regain its original gross anatomical structure. Remnant liver proliferates to meet metabolic needs of the organism. During liver regeneration, quiescent hepatocytes undergo one or two rounds of replication and then return to non-proliferative state. Based on physiological effects of pine needle previously mentioned, in this study, effects of pine needle extract (PNE) were investigated in regenerating rat liver. To determine the positive effects of PNE on liver regeneration induced by PH in rat, PNE was administrated to animal model and then the effects were investigated focused on protein expression which is related with cell proliferation. Juicy PNE was stored at 4℃ for 3 years before used. Rats in experimental group were provided PNE which was diluted in distilled water at 10% from 5 days before PH till sacrifice. As results, it was microscopically observed that hepatic plates were collapsed and restored during liver regeneration. Hepatocytes were divided and then hepatic structure was restored with proliferation of endothelial cells and remodelling of sinusoidal network. Vascular endothelial growth factor-A (VEGF-A) played a crucial role in this process. In serum analysis, AST and ALT activity of experimental group increased in early phase of liver regeneration. But the activities recovered within one day. In immunohistochemistry, Ki-67 which is used for biomarker to proliferation expression in hepatocyte obviously increased. It means that PNE promotes proliferation of hepatocyte. In western blot analysis, proliferating cell nuclear antigen (PCNA) expression was also relatively accelerated. PCNA expression in experimental group was peaked at 36 hrs after PH while in control group, the expression was peaked at 60 hrs after PH. In experimental group, VEGF-A expression increased quickly after PH and continued to 3 days. In rodent, proliferation of endothelial cells to restore the sinusoids occurs from 3 days till 6 days after PH. It has been reported that DNA synthesis of VEGF-A was started at 12 hrs after PH and peaked at 48 hrs. In this study, VEGF-A already increased at 12 hrs after PH. This pattern is thought to be due to the stimulation of PNE and then increased VEGF-A could accelerate the proliferation of non-parenchymal cell and restoration of sinusoid. Remodeling of sinusoid in early stage facilitates to carry nutrients and oxygen and other signal molecules for proliferation of hepatic cells. In summary, administration of PNE stimulates the expression of VEGF-A in regenerating liver and then restoration and development of sinusoidal network were promoted. These changes could promote the proliferation of hepatic cells through supplying of sufficient nutrients and oxygen. These results in early phase of liver regeneration could bring insight into the physiological events of liver and liver transplantation and would be applied to medical treatment. Further trials such as identifying of core component are asked for complete understanding the effects of PNE on regenerating liver.

Bone regeneration with biomaterials for protein delivery and stem cell differentiation

나완근 서울대학교 대학원 2012 국내박사

The current study is reporting on the tissue engineering of bone tissue regeneration using bone morphogenetic protein -2 (BMP-2) delivery, stem cell transplantation and drug delivery. Previous bone fracture patients were treated with autograft, allograft and xenograts implantation. However these grafts have some disadvantages. Autografts have the distinct advantage of histocompatibility without the risks of disease transfer and are still the best material for bone repair. However, their limited availability necessitates the development of alternative bone substitutes. Although allogenic bone grafts have better availability than autografts and avoid the need for a second surgical procedure to obtain an autograft, the use of allogenic bone grafts may transmit diseases and cause immune responses, which lead to the graft failure. Recently, BMP-2 is being used clinically to regenerate bone tissue instead of graft implantation. However BMP-2 has several limitations for successful bone regeneration. Another tissue engineering approach of bone regeneration is to use bone marrow mesenchymal stem cells (BMMSCs) that represent a promising bone substitute for repairing large bone defects. Nevertheless, undifferentiated BMMSCs are not sufficient for in vivo bone formation without predifferentiaion. Therefore, in this study we investigated the appropriate factors for BMP-2 delivery vehicle and developed methods for enhancing BMMSCs in vitro and in vivo osteoblastic activity. Following the introductory description and experimental procedures in chapter 1 and 2, we investigated the dependency of the orthotopic bone formation efficacy of BMP-2 at various doses on its delivery mode in chapter 3. Heparin-conjugated poly (lactic-co-glycolic acid) nanospheres suspended in fibrin gel were used as a long-term delivery system, and fibrin gel was used as a short-term delivery system. Various doses of BMP-2 was delivered to mouse calvarial defects using either the long-term delivery system or the short-term delivery system. Eight weeks later, bone regeneration was evaluated with X-ray radiopacity and histomorphometry. For both delivery systems, bone regeneration increased as the BMP-2 dose increased up to 1 μg, and beyond this dose (1 μg) the bone regeneration did not increase further. Importantly, at BMP-2 dose higher than 1 μg, the long-term delivery exerted much greater bone formation compared to the short-term delivery. This study shows that long-term delivery of BMP-2 enhances orthotopic bone formation compared to short-term delivery at various doses. In chapter 4, we compared the quality of regenerated bone when BMP-2 was delivered with either β-tricalcium phosphate (β-TCP) or heparin conjugated fibrin (HCF), both of which are shown to be excellent carriers for BMP-2. The release profile of BMP-2 was not significantly different between the delivery carriers. However, the alkaline phosphate activity (ALP) of cultured osteoblasts was significantly higher when BMP-2 was delivered using HCF than when BMP-2 was delivered using β-TCP. To evaluate the quality of the regenerated bone, both types of BMP-2 carriers were implanted into critical-sized calvarial defects in mice. Eight weeks after implantation, the regenerated bone was examined by histomorphometry. Importantly, the treatment using HCF+BMP-2 and β-TCP+BMP-2 resulted in similar bone formation areas. However, the treatment using HCF+BMP-2 resulted in significantly higher bone density than the treatment using β-TCP+BMP-2. This study shows that a BMP-2 delivery carrier can modulate the quality of bone regenerated via BMP-2 delivery. In chapter 5, we improved clinically utilized BMP-2 using a type-I collagen scaffold with apatite coated on the surface. Apatite coated was achieved by incubating collagen scaffolds in simulated body fluid. BMP-2 release kinetics and bioactivity were evaluated by enzyme-linked immunosorbent assay and alkaline phosphatase activity (ELISA) measurement of cultured osteoblasts. Micro-computed topography (Micro-CT) and histomorphometry were performed eight weeks after various doses of BMP-2 were delivered to mouse calvarial defects using either non-modified or apatite-coated collagen scaffolds. Apatite-coated collagen scaffolds released 91.8 ± 11.5% of the loaded BMP-2 over 13 days in vitro, whereas non-modified collagen scaffolds released 98.3± 2.2% over the initial one day. The in vivo study showed that BMP-2 delivery with apatite-coated collagen scaffolds resulted in a significantly greater bone formation area and higher bone density than that with non-modified collagen scaffolds. This study suggests that simple apatite coating on collagen scaffolds can enhance the bone regeneration efficacy of BMP-2 released from collagen scaffolds. In chapter 6, the study was to compare the bone-forming ability of the BMP-2 delivered by HCF to that delivered by clinically utilized BMP-2 delivery vehicle collagen sponge. An in vitro release profile of BMP-2 showed that HCF released 80% of the loaded BMP-2 within 20 days, whereas collagen sponge released the same amount within the first 6 days. Moreover, the BMP-2 released from the HCF showed significantly higher ALP activity than the BMP-2 released from collagen sponge at 2 weeks in vitro. Various doses of BMP-2 were delivered with HCF or collagen sponge to mouse calvarial defects. Eight weeks after the treatment, bone regeneration was evaluated by computed tomography, histology, and histomorphometric analysis. The dose of BMP-2 delivered by HCF to achieve 100% bone formation in the defects was less than half of the BMP-2 dose delivered by collagen sponge to achieve a similar level of bone formation. Additionally, bone regenerated by the HCF-BMP-2 had higher bone density than bone regenerated by the collagen sponge-BMP-2. These data demonstrate that HCF as a BMP-2 delivery vehicle exerts better osteogenic ability of BMP-2 than collagen sponge, a clinically utilized delivery vehicle. In chapter 7, we investigated whether modifying culture surface with 3,4-Dihydroxy-L-phenylalanine (DOPA), can enhance in vitro osteogenic differentiation of human bone marrow-derived mesenchymal stem cells (hBMMSCs). hBMMSC cultured on DOPA-coated plates exhibited better cell adhesion and spreading compared to that on non-coated, conventional tissue culture plates. DOPA coating did not affect apoptosis and viability of the cultured hBMMSCs. hBMMSCs on DOPA-coated plate exhibited higher degree of osteogenic differentiation than those cultured on non-coated plate, as evaluated by ALP activity, calcium content, and mRNA expression of runt-related transcription factor 2 (Runx2), ALP, and osteocalcin. hBMMSCs cultured on DOPA-coated plates exerted higher capability of ectopic bone formation in vivo following implantation to subcutaneous space of athymic mice than those cultured on non-coated plate, as evaluated by micro-CT analysis and histomorphometry. These results indicate that modifying culture surface with DOPA can enhance in vitro osteogenic differentiation of hBMMSCs.

An Analysis of Financial and Physical Incentives on Urban Regeneration Projects in the Metropolitan Area of Japan : Focusing on Kawasaki Station Urban Regeneration Cases

권구황 서울시립대학교 대학원 2009 국내석사

Even though Japan had been experiencing dramatic growth in its economy by the late 1980s, they also had to face striking economic recession over the whole country after the bubble of Japanese economy started busting. Both their prices of houses on the market and the price index of stocks fell remorselessly and never seemed to bottom out. From that time for ten years, Japan experienced long-term recession called as “lost ten years." To overcome this, Japan had driven many policies, and one of them called as “urban regeneration” started in 2001 when the Ministry of Koizumi Junichiro took the office. It was true that Japanese urban regeneration was devised to pull its economy in booming stage again. And by regenerating cities Japan could get not only economic vigor but also perfectly new cities considered to have more competitiveness now. Without vitality of private sector, urban regeneration project cannot fulfill the creativity and show their ideas to the public. Historical events also show that funds and ideas of the private are one of the most critical factors which can lead a project to more successful development. In this aspect, Japan is well known for giving various incentives on urban regeneration cases to generate private companies' participation. This paper aimed at both analyzing the strategies of urban regeneration in Japan through case study and drawing the implication suitable to Korea. By taking a closer look to the Kawasaki Station’s two urban regeneration cases : Lazona Kawasaki Project and Muza Kawasaki Project, this study focused on the incentives the private and public developers could get. In the cases, there were a few incentives the developers took advantage of. First, they took physical incentives which helped the developers change the former land use, so that they could use the land in more effective and efficient way. Given that the changes into large commercial area help the local government revitalize their regional economy and renew the district, this can be an effective way of using demolished industrial plant. Second, giving financial incentives to the regeneration projects also helped the private be a part of the regeneration project. Especially, unique scheme like urban regeneration fund made the developer have easy access to fund-raising from commercial banks and private sectors Third, a long term and comprehensive plan made the two projects better developed. Making detailed plan and discipline on redevelopment as well as giving more opportunity to participate in regeneration cases led to more effective and efficient land use and convenient way of life for citizens. However, in that each incentive system has its own strength and weakness, more complicated studies would be needed to understand the Japanese urban regeneration and to apply the incentive system into Korea. 패전 이후 일본은 1980년대 후반까지의 급속한 경제성장을 통해 초 일류국가로서의 기틀을 마련하였지만 1990년대 초반의 거품경제의 붕괴 이후로 10년 동안 경기침체를 경험하였고, 이 시기동안 부동산뿐만 아니라 주식시장 역시 붕괴되었다. 이러한 거품경제의 붕괴를 극복하기 위하여 일본정부는 다양한 시도를 해 왔고, 그 일환으로써 2001년 고이즈미 내각 당시 도시재생본부를 발족하고 도시재생을 실현하기 위한 정책을 실시해오고 있다. 이를 통해 일본정부는 경기활성화와 동시에 도심공간의 재활성화라는 두 가지의 목표를 달성하기 위해 노력하고 있다. 도시재생과 같이 막대한 자금이 필요한 사업에 있어서 공공의 자금만을 가지고 사업을 추진하기에는 큰 위험과 무리가 따르고 있기 때문에 민간의 활력과 자금을 확보하는 것이 무엇보다 중요하다고 할 수 있을 것이다. 이러한 측면에서 일본은 민간과 공공의 사업참여를 유도하기 위한 다양한 인센티브를 마련함으로써 도시재생을 원활히 추진하기 위해 노력하고 있다. 이에 본 연구는 일본의 도시재생정책의 추진배경과 의의를 보다 구체적으로 살펴보고, 도시재생을 유도하기 위한 다양한 지원제도를 살펴보기 위해, 사례지역을 선정하여 인센티브를 분석함으로써 시사점을 찾고자 하는데 있다. 구체적인 인센티브 및 시사점은 다음과 같다. 첫째, 용도변경의 허가를 통해 공장이전적지 및 저·미이용지의 효율적 활용을 도모하였다. 특히 호리가와쵸공장부지의 경우 공장이전적지를 대규모 상업공간으로 변화시킴으로써 지역경제에 큰 파급효과를 미치고 있었다. 한국의 경우, 공장이전적지의 용도전환에 있어서 녹지위주의 변환 혹은 주상복합의 개발을 통해 주거위주의 개발이 이뤄져왔다는 점에서 본 사례는 의의가 크다고 할 수 있다. 둘째, 도시재생사업의 원활한 사업자금을 확보하기 위해 민간도시개발기구와 일본정책투자은행의 도시재생펀드를 활용하고 있는데, 본 사례는 일본정책투자은행과 미즈호 은행이 공동 투자한 도시재생펀드를 통해 후순위 채권에 자금이 투입되면서 사업이 보다 원활히 진행될 수 있었다는 특징이 있다. 이러한 공공과 민간의 펀드를 바탕으로 한 도시재생사업의 투자는 종래 행해지고 있는 다른 자금조달 방식과 차이점을 보인다는 점에서 의의가 클 것이다. 셋째, 일본의 경우 도시재생을 촉진하기 위해 도시재생긴급정비지역의 지정을 통해 사업의 추진을 돕고 있다. 하지만 하나의 제도를 바탕으로 도시재생사업이 진행되는 것이 아니라, 다른 다양한 정책들의 유기적 지원을 통해 도시재생을 보다 빠르고 강력하게 추진하면서도, 종합적인 규제의 틀을 마련하여 체계적인 개발이 될 수 있도록 하고 있다. 그렇지만 이러한 인센티브 역시 각각의 장·단점을 지니고 있으며 이를 분석하기 위해서는 보다 많은 연구가 진행되어야 할 것이다. 특히 본 연구가 선택한 사업의 경우 다양한 제도가 중첩되어 적용되고 있고, 사례지역의 수 역시 두 개로 한정되어 있어 일본의 도시재생정책의 대표적인 사례라고 단정 짓기 어려우며, 사례지역에 적용된 제도적 수법을 살펴보았을 뿐 이로 인한 경제적 파급효과 및 그 결과에 대해서는 다루지 못했다는 연구의 한계를 지니고 있다. 따라서 일본이 부동산 및 경제의 버블 붕괴이후 극복의 방법으로 제시한 도시재생사업을 보다 구체적으로 연구하고, 그 파급효과를 바탕으로 한국에의 시사점을 도출할 수 있는 연구가 지속적으로 이뤄지기를 바란다.

Community formation and spatio-temporal implication in residential area regeneration project : a case study of the government R&D test-bed project in Changwon

이상훈 Graduate School, Yonsei University 2017 국내박사

Local governments have been implementing various urban regeneration project with support of the government since legislation of the Special Act on Promotion of and Support for Urban Regeneration in June 2013. Regeneration of residential areas takes up important part in urban regeneration projects and the success of residential area regeneration hangs largely with formation of communities. However, this formation of communities is not made easy due to conflicts between redevelopment and regeneration that normally occur in early stages of regeneration projects, and hence much time is required for community formation and for the regeneration project as a whole. In addition, a project that is executed within the framework of regeneration project but aims for different types of spaces than those sought by the community weakens aims of regeneration and sometimes have negative effects on regeneration. This research takes a look at regeneration of residential area in Nosan-dong, Changwon, to examine conflicts that arise during community formation process and characteristics and sustainability of community that is formed upon resolution of conflicts, on one hand. On the other hand, spatial - spatio-temporal - characteristics and implications of regeneration projects are examined to distinguish conservation oriented regeneration projects and non-conservation but development resulting other projects from spatial perspectives, and, farther, to gain a spatio-temporal understanding about Korean cities in general. A number of different conflicts arose in the process forming Nosan-dong residential area regeneration community: conflicts between residents wanting redevelopment and research team implementing the regeneration project, conflicts between residents for redevelopment and residents for regeneration, and conflicts between residents who were members of existing community groups and the rest of the residents. These conflicts were resolved with formation of strong emotional solidarity based on mythical metaphorical field between research team and residents and early visible actualization of project effects via residential welfare type of regeneration. Resolution of conflicts enabled the birth of a formidable community known as town corporation at the suggestion of research team. This leads to the summary that role of experts, small short-term projects that can prove benefits of regeneration, and appropriate utilization of existing groups are essential in residential area regeneration. Projects executed by the community basically tried to conserve existing spaces and have heterotopic characters. Existing space’s spatial composition is retained to conserve placeness and diversity, to bolster continuity of alleys, to alleviate spatial tension through use of vacant spaces, and to encourage spontaneous links of adjacent parts. Only, it was observed that the alleys were not used as living spaces any longer with increasing number of outsiders visiting the alleys. Meanwhile, new roads constructed under the residential environment improvement project and development of town square and public parking lot under the Doshi-hwallyuck-jeungjinjiyuck-gaebal-saup(urban vitality promotion regional development project) led to a Haengbok housing project - a public housing project - resulting in a space prompts homotopic development that was not intended by the regeneration project. This, in turn, has led to rise in housing values in Nosan-dong inducing many outsiders to move to Nosan-dong and this has been shown to furnish causes for recurrence of redevelopment and regeneration conflicts. A range of spatio-temporal implications comprising spaces created by a community in the Nosan-dong regeneration project painstakingly revealed characteristics of Korean cities in general. The most important of these is active referencing of nature. Referencing to cyclical nature and recurrence to nature had the effect of emotionally binding not only residents but also outsides in ecological and metaphoric manner. Because the center of a city – town square – is left empty and because physical boundaries of a community are determined by social space, physical boundaries are ambiguous and have tendency to broaden. The fact that ambiguous boundaries became clearer with the regeneration project receiving financial support and that conflicts between resident factions arose is worthwhile noting. Identity of a community grounded in relationships so that it has tendency to even use other region’s resources to expand network of relationships and to increase its value. And, the unruly and disorderly looking urban space was not an object to be looked at but a living space so that the disorderliness had not raised landscape issues with the residents. Community’s non-spatial enterprises, town corporations and town festivals, provide strongly ludic space-times in character. These space-times have boundaries, rules and order distinguishable from daily life and had enthusiastic participation of residents on voluntary basis under utopian goal known as urban regeneration. Points to be made about these space-times are that they are less restricted by physical space due to their temporal features and that they are very similar to ludic space-times with narcissistic tendencies being made immensely popular by young people. Book café that opened as town corporation #2 while serving its intended communal purposes also needs to embrace the narcissistic ludic space-times of young people by making use of internet, blogs and etc. Sustainability of a community lies in capturing goal-oriented ludic space-times accompanied by flexible and elastic physical space.

TAZ stimulates muscle regeneration by Myf5 induction and prolonged TAZ increase promotes muscle fibrosis in muscular dystrophy

김경민 Graduate School, Korea University 2020 국내박사

Damaged muscle is repaired by activation of satellite cells, known as muscle stem cells, by regeneration signals. However, this activation mechanism remains largely unknown. Here, I demonstrated that transcriptional coactivator with PDZ binding motif (TAZ) promotes muscle regeneration via satellite cell activation. During muscle regeneration, TAZ expression is significantly increased in satellite cells, promoting satellite cell proliferation, and when TAZ is depleted from satellite cells, muscle regeneration is delayed. This is because TAZ interacts with Pax7 to induce the expression of Myf5, which stimulates satellite cell activation. TAZ expression also is remarkably increased in muscles of Duchenne muscular dystrophy patients and mdx mice. In early stage muscular dystrophy, satellite cell specific TAZ knockout mdx mice (mdx;sKO) are defective in muscle regeneration due to reduced satellite cell activation. Unlike this, prolonged satellite cell TAZ activation in late stage muscular dystrophy causes muscle fibrosis via TGFβ2 induction. These results suggest a novel mechanism of satellite cell activation and muscle fibrosis by TAZ. In addition, alleviation of muscle fibrosis in mdx mice treated with simvastatin that reduces TAZ indicates TAZ as a target of treatment.

Research on Urban Regeneration Strategy on Spatial Arrangement under the Background of Inventary Age : Case Study of the Northern Region of Changchun Railway Station, China

HU, Yuan University of Seoul, International School of Urban 2021 국내석사

최근 수십 년 동안 중국은 급속한 인구 집중과 토지 확장을 경험했는데, 이는 수많은 ""도시 질병""을 유발했다. '뉴 노멀'시대 진입 후, 중국의 도시 재생은 특정 단계에 이르기 위한 다양한 도시 개발 방법 중 하나이며, 도시의 공간/구조와 기능 재생을 위한 과정이다('뉴 노멀'의 개념은 2014년 시진핑 중국 주석이 제시한 것으로, 주로 중국의 경제 발전 모델이 양에서 질로 전환하는 것을 의미한다). 따라서 도시 재생은 의심할 여지없이 도시의 지속가능한 개발을 촉진하는 중요한 분야가 될 것이다. 도시 재생은 도시 문제를 해결하고 도시 지향성을 실현하며, 실행 가능성을 보장해야 한다. 도시 재생에는 주로 4개의 연구 포인트가 있다. 첫째, 도시 개발의 문제 및 목표에 대한 이해. 둘째, 문제와 목표에 기반한 도시 재생 전략 모색. 셋째, 기존 도시 계획 시스템과 연결. 넷째, 재생 계획의 이행을 보장하기 위한 정책 및 시스템 구축이다. 본 연구에서는 문헌연구법, 분석 및 비교법, 현장 조사법, 사례 연구법, 차트 분석법의 5가지 연구 방법을 채택하였으며, 중국의 비축 시대(Stocking of era) 도시 재생 사례로 장춘역 북구 재생을 설명한다. 본 연구는 미래 가치를 위해 비축 시대 도시 재생의 적용 방법을 모색하는 일환으로 국내외 개발의 역사 및 관련 이론과 중국의 고유한 상황을 결합하여, 실제 프로젝트를 연구 대상으로 삼아 토지이용, 교통 조직, 도시 기능, 경관 환경 조성 등의 측면에서 재생 전략을 제시한다. 주요어: 비축 시대(Stocking of era), 도시 재생, 기획 전략, 장춘역 북부 지역, 공간 구문 In recent decades, China has witnessed rapid population agglomeration and land expansion, which has brought many urban problems to cities. After entering the ""new normal"" era which refers to the transformation of China's economic development model from quantity to quality, urban regeneration in China also keep pace with this by promoting more sustainable ways of urban development. The research objective of this thesis is to summarize and explore the referable model of urban regeneration in the inventory era in China through the experience, principles and methods of the urban regeneration project of Changchun Railway Station Northern Region conducted by the project team led by myself. To provide more feasible experience and suggestions for more urban regeneration projects in terms of four important parts, spatial structure, urban functions, transportation system and landscape environment. This study adopts 5 kinds of Research Methods: literature review, case comparison, site investigation, chart analysis and space syntax. In this thesis, four key aspects of urban regeneration are studied. Through the study and reference of urban regeneration related cases, the comparison of domestic and foreign urban regeneration actual project methods, in-depth field questionnaire and research, the production of relevant diagrams and tables, and the use of space syntax analysis to draw the corresponding conclusions, these five ways to conduct a comprehensive study. Through the research of this thesis, it is found that under the background of ""new normal"" era, urban regeneration projects have common and reproducible methods to enhance the overall style, function and business form of the city and the vitality of the city. There are four key strategies to perfect the urban regeneration. For example, through optimize spatial structure make the city's skeleton and street grid scale clearer. Through perfect the urban functions, cancel the functions that are not suitable for the current urban development rhythm, and implant the urban functions that are more in line with the actual situation and the future development trend of the city. Through adjustment the transportation system in order to make the city traffic smoother, people reach the destination more convenient, the city road more humanized. Through improve landscape environment in order to improve the beautiful urban environment and create green ecological space. By focusing on the four aspects of urban regeneration, we can improve the quality of the city and create a beautiful space more suitable for human living. Keywords: urban regeneration, planning strategy, Changchun Railway Station Northern Region, space syntax