Automated Vascular Smooth Muscle Segmentation, Reconstruction, Classification and Simulation on Whole-Slide Histology

Histology of the microvasculature depicts detailed characteristics relevant to tissue perfusion. One important histologic feature is the smooth muscle component of the microvessel wall, which is responsible for controlling vessel caliber. Abnormalities can cause disease and organ failure, as seen in hypertensive retinopathy, diabetic ischemia, Alzheimer’s disease and improper cardiovascular development. However, assessments of smooth muscle cell content are conventionally performed on selected fields of view on 2D sections, which may lead to measurement bias. We have developed a software platform for automated (1) 3D vascular reconstruction, (2) detection and segmentation of muscularized microvessels, (3) classification of vascular subtypes, and (4) simulation of function through blood flow modeling. Vessels were stained for α-actin using 3,3\u27-Diaminobenzidine, assessing both normal (n=9 mice) and regenerated vasculature (n=5 at day 14, n=4 at day 28). 2D locally adaptive segmentation involved vessel detection, skeletonization, and fragment connection. 3D reconstruction was performed using our novel nucleus landmark-based registration. Arterioles and venules were categorized using supervised machine learning based on texture and morphometry. Simulation of blood flow for the normal and regenerated vasculature was performed at baseline and during demand based on the structural measures obtained from the above tools. Vessel medial area and vessel wall thickness were found to be greater in the normal vasculature as compared to the regenerated vasculature (p\u3c0.001) and a higher density of arterioles was found in the regenerated tissue (p\u3c0.05). Validation showed: a Dice coefficient of 0.88 (compared to manual) for the segmentations, a 3D reconstruction target registration error of 4 μm, and area under the receiver operator curve of 0.89 for vessel classification. We found 89% and 67% decreases in the blood flow through the network for the regenerated vasculature during increased oxygen demand as compared to the normal vasculature, respectively for 14 and 28 days post-ischemia. We developed a software platform for automated vasculature histology analysis involving 3D reconstruction, segmentation, and arteriole vs. venule classification. This advanced the knowledge of conventional histology sampling compared to whole slide analysis, the morphological and density differences in the regenerated vasculature, and the effect of the differences on blood flow and function

Local induction of lymphangiogenesis with engineered fibrin-binding VEGF-C promotes wound healing by increasing immune cell trafficking and matrix remodeling

Lymphangiogenesis occurs in inflammation and wound healing, yet its functional roles in these processes are not fully understood. Consequently, clinically relevant strategies for therapeutic lymphangiogenesis remain underdeveloped, particularly using growth factors. To achieve controlled, local capillary lymphangiogenesis with protein engineering and determine its effects on fluid clearance, leukocyte trafficking, and wound healing, we developed a fibrin-binding variant of vascular endothelial growth factor C (FB-VEGF-C) that is slowly released upon demand from infiltrating cells. Using a novel wound healing model, we show that implanted fibrin containing FB-VEGF-C, but not free VEGF-C, could stimulate local lymphangiogenesis in a dose-dependent manner. Importantly, the effects of FB-VEGF-C were restricted to lymphatic capillaries, with no apparent changes to blood vessels and downstream collecting vessels. Leukocyte intravasation and trafficking to lymph nodes were increased in hyperplastic lymphatics, while fluid clearance was maintained at physiological levels. In diabetic wounds, FB-VEGF-C-induced lymphangiogenesis increased extracellular matrix deposition and granulation tissue thickening, indicators of improved wound healing. Together, these results indicate that FB-VEGF-C is a promising strategy for inducing lymphangiogenesis locally, and that such lymphangiogenesis can promote wound healing by enhancing leukocyte trafficking without affecting downstream lymphatic collecting vessels. (C) 2017 The Authors. Published by Elsevier Ltd

탈산업 도시의 경관 진정성

학위논문(박사) -- 서울대학교대학원 : 환경대학원 협동과정 조경학, 2023. 2. 배정한.This thesis begins with a question, how can we understand and utilize the power of landscape authenticity, given the context of post-industrial city and the increasing commodification of urban landscapes? This question is founded on the idea that the contemporary issues stem from a complex network of interests and desires that operate the urban society. This thesis believes that landscape authenticity is part of such an operation that is visible in our everyday lives. When considering landscape authenticity, the issues typically discussed in relation to urban revitalization of the post-industrial city such as urban homogeneity, gentrification and overtourism are in fact the by-products of the process where landscape authenticity is formulated, recognized, and appropriated by the cultural entrepreneurs, urban regeneration experts, municipal governments, residents, and the non-residents. However, a critical issue faced by the landscape authenticity discourse, particularly those who are trying to find ways of applying the concept to the post-industrial city, is that the existing definition and scope the concept does not sufficiently encompass the expanding field of landscape authenticity. Hence, in hopes of providing a suitable answer to the proposed question, this thesis covers a wide variety of topics related to urban landscape authenticity to illustrate the fluid and undefined nature of the concept, to provide a framework that allows for a wider spectrum of landscape authenticity to be included into the discussion of contemporary cities, to demonstrate how its uncritical application in the post-industrial urban revitalization sites can be disruptive to sustainable urban development, and to propose ways of harnessing landscape authenticity to in ways that include a diverse array of authentic representations that are authenticated through different consumer agencies. First, this thesis aims to update and clarify the concept of landscape authenticity in the context of post-industrial city. The definition of landscape authenticity is necessarily complex and contextual. For the purpose of the discussions presented here, this study defines landscape authenticity as conspicuous representation of authentic qualities of a site in a specific landscape, where authentic qualities are qualities or elements that are authenticated by the landscape consumers. Because our society is collecting resources from every corner of the earth in similar, if not uniform fashion, it is unlikely that any land can be described as untouched or pristine. This means that one cannot place the different representations of landscape authenticity into a hierarchical frame. Instead, the Three Layers of Landscape Authenticity, an analytical framework for understanding different layers of authenticity that are found on site, is presented as an alternative approach. Divided into site-specific, constructive, and projective authenticities, the framework is designed so that all types of authenticity representations, from natural and historical to innovative and idiosyncratic, may be included. A key agent in the discussion over urban landscape authenticity is the landscape consumer, whose agency is influential through the process of authentication. Landscape consumers are the main agents of authentication process, which refers to a process of aesthetic engagement with the site in terms of landscape authenticity. This process allows for landscape authenticity to be in constant flux in accordance with the society. Since the authentication of a landscape authenticity representation relies on the consumer, landscape authenticity functions as both index and icon, shifting from a reference to a realized architectural form, only to be adapted as a reference for other sites. In other words, landscape authenticity is an ever-evolving repository that is necessarily attached to the site. Not all representations of landscape authenticity are conspicuous; considering the linearity of time, the most recent additions to the landscape, either idiosyncratic, iconic, or else, are more visible in urban settings. However, projective authenticity, due to its attachment to consumers, is subjected to political intentions that appropriate landscape authenticity in ways that do not consider the longevity of the complex relationship between the landscape authenticity layers. In this thesis, two examples, the Seoul Forest Alleys and the Huinnyeoul Culture Village, were analyzed to attest to such a situation. Based on the analysis of two sites, issues regarding policy, agency, and understanding of landscape were identified. The image-specific landscape policies that are prone to projective authenticity have tendency to overwhelm the future landscape with little to no regard for other distinct layers of landscape authenticity on site. In place of establishing image-specific landscape policies, this thesis proposes a more thorough survey of landscape authenticities by using the framework of the Three Layers of Urban Landscape Authenticity. Key function of this framework is to balance the consumer agency behind each layer and to create a more integrative archive of the site. This means that urban landscape authenticity as presented in this thesis may function as a platform from which interdisciplinary discussion regarding landscape may arise. This allows for landscape authenticity to remain in flux, updating itself through communication with the consumers, and to stay relevant for future landscape-related projects. With many cities in developing nations shifting from manufacturing into service industry, different forms of urban regeneration will likely continue in different contexts. The topics and issues discussed in this paper may provide insight into how landscape authenticity functions in relation to the contemporary society, and how the induction of tourism industry through political measures in a residential site can cause confusion in terms of representation of authenticity. Finally, the extensive literature review conducted throughout this thesis that connects various fields in introducing and discussion the concept of urban landscape authenticity will lead other landscape and/or landscape architecture research to consider the concept of authenticity and take initiatives in formulating interdisciplinary network of ideas.전 세계를 주도하는 산업 패러다임이 바뀐 이후 도시의 재생과 재활성화는 선택이 아닌 필수가 되었다. 그 과정에서 도시화 및 산업화를 통해 상실한 도시의 크고 작은 문화사회적 자본을 보존하고자 하는 노력이 진정성에 대한 논의로 이어지고 있다. 하지만 도시에서 진정성이란 새로운 것, 완전히 전례가 없는 것으로도 나타난다. 다양한 형태의 진정성이 탈산업 도시의 경관 곳곳에 존재하고 있으며, 다양한 학문 및 실천 분야가 진정성의 요소를 구체적인 상으로 발전시켜 도시 개발, 보존 사업, 상업 프로젝트 등으로 전환하고 있다. 본 연구는 오늘날 도시를 둘러싼 많은 문제의 뿌리에 도시를 향유하고 작동하는 다양한 욕망이 존재한다고 파악하고 있으며, 그 작동 기제 중 하나로 경관의 진정성에 주목했다. 경관 진정성을 도시가 지닌 작동 기제의 가시적 형태라고 본다면, 오늘날 도시의 문제점으로 종종 언급되는 동질화, 젠트리피케이션, 오버투어리즘 등 역시 문화 창업가, 도시재생 전문가, 지자체의 행정, 주민과 비주민 모두에 의해 경관 진정성이 형성되고 인지되고 활용되는 과정의 부작용이라고 볼 수 있다. 그러나 경관 진정성은 여전히 난해한 개념으로 남아 있다. 특히 오늘날 경관 진정성을 연구하거나 실천으로 옮기는 데 있어 문제가 되는 것 중 하나는 현재 도시 연구 분야에 적용되고 있는 경관 진정성 개념이 탈산업 도시의 맥락과 현상을 충분히 포괄하지 못한다는 점이 있다. 따라서 탈산업 도시의 경관 진정성에 대한 탐구를 위해 본 연구는 도시 경관의 진정성을 다루는 다양한 분야의 연구를 정리하고, 현대 도시 경관의 진정성을 분석하기 위한 연구 틀을 구축하고, 적확한 경관 진정성 적용의 중요성을 드러내는 사례를 분석하며, 다양한 경관 진정성 개념을 탑재해 경관 실천으로 연계하기 위한 방안을 제시하고자 한다. 먼저 탈산업 도시의 맥락에서 경관 진정성 개념을 재설정하여 범주와 적용 대상을 확장할 필요가 있다. 본 연구의 논의를 위해 경관 진정성(landscape authenticity)이란 특정 경관에서 부지의 진정한 특질(authentic qualities)을 나타내는 가시적 재현이라고 파악한다. 여기서 진정성은 경관의 소비자에 의해 인증(authenticate)된다. 인증 과정으로 인해 경관 진정성은 계속해서 변화를 겪게 되는데, 인증의 주체인 소비자가 계속해서 변화하기 때문이다. 이러한 특성으로 인해 경관 진정성은 기표이자 기호로 작동하며 경관을 둘러싼 다양한 내러티브를 축적하게 된다. 탈산업 도시는 산업화가 낳은 다양성의 상실이라는 공통 증상을 겪고 있으며, 이에 따라 소비자로 인해 인증된 경관 진정성은 이동하고 투영될 수 있다고 보았다. 즉, 경관 진정성의 다양한 재현은 층위적 구조를 갖고 있되, 구조 및 각 켜의 위치가 고정되어 있지 않다. 본 연구는 이를 반영하기 위해 경관 진정성 켜를 세 가지 유형으로 구분했다. 다음으로, 장소특정적(site-specific), 구성적(constructive), 투영적(projective) 진정성으로 구성한 본 연구의 경관 진정성 분석모델을 통해 서울숲길 일대와 부산 흰여울문화마을 일대의 경관을 분석했다. 두 사례지를 분석한 결과, 경관 관련 정책, 행위성, 경관 이해 등에서 문제점을 발견했다. 경관 진정성의 다양한 켜가 아닌 이미지를 위시한 투영 진정성 중심의 정책 실천으로 인해 경관 진정성의 다른 켜에 부정적 영향을 미치거나 상실로 이어질 수 있다는 문제도 도출했다. 이에 대응하기 위해서 본 연구가 제시한 경관 진정성 분석모델을 통해 다양한 켜를 축적하는 효용성 있는 아카이브를 구축하는 것이 중요할 것이다. 마지막으로, 본 연구는 유연함과 변화무쌍함이 경관 진정성을 유의미하게 만들며 경관 실천에 영향을 미칠 수 있을 것이라 해석했다. 실제로 전통적으로 경관을 연구해온 지리학과 조경학이 아닌 관광학과 경영학을 중심으로 최근 경관 진정성 연구가 발전했다는 점에 주목할 필요가 있다. 경관 진정성 개념을 중심으로 한 다학제적 연구를 통해 경관 연구의 확장이 가능할 것이다. 제조업에서 서비스업으로, 서비스업에서 지식산업으로 계속해서 산업이 바뀌는 과정에서 도시의 구조와 경관 역시 변화를 피할 수 없다. 본 연구는 현대 사회에서 경관 진정성이 어떻게 작동하고 있으며 경관을 바꿀 힘을 가진 정책이 경관 진정성과 어떻게 결합되고 어떤 결과를 낳고 있는지 비판적 시선으로 고찰했으며, 이를 바탕으로 대안적 연구 틀과 제언을 제시함으로써 이론적실천적 함의를 도출했다. 나아가 본 연구를 구성하는 다양한 문헌 분석은 추후 탈산업 도시의 경관과 진정성 연구의 다변화와 다학제적 연구의 확장을 위한 바탕이 될 것으로 기대한다.Ⅰ. INTRODUCTION 1 1.1. Research Background 1 1.2. Research Purpose 9 1.3. Research Perspective 11 1.3.1. Lacanian Alienation and Authenticity 11 1.3.2. Postmodernism and Pseudo-modernism 14 1.4. Research Scope & Methodology 17 1.4.1. Scope 17 1.4.2. Methodology 20 1.4.3. Organization 23 Ⅱ. DEVELOPMENT OF THE LANDSCAPE AUTHENTICITY IDEA 26 2.1. The Historical-Philosophical Development of Authenticity 27 2.1.1. Why (Urban Landscape) Authenticity, Now 27 2.1.2. Development of Authenticity Discourse since the 18th Century 31 2.1.3. From Innate to Acquired Quality 34 2.2. Authenticity and Landscape 37 2.2.1. Authenticity in Heritage and Tourism Studies 41 2.2.2. Authenticity in Entrepreneurship and Consumer Studies 48 2.2.3. Authenticity in Urban Studies and Design Fields 53 Ⅲ. A NEW FRAMEWORK FOR LANDSCAPE AUTHENTICITY 69 3.1. Review of Urban Landscape Authenticity Categories 69 3.1.1. From Authentic Tourist Experiences to Authentication 69 3.1.2. Indexical and Iconic Authentications 72 3.1.3. Interpretation of Authenticities in Commercial Landscapes 75 3.1.4. Authenticity Triad in Urban Planning 79 3.2. The Three Layers of Urban Landscape Authenticity in the Post-Industrial Urban Context 82 3.2.1. Site-specific Authenticity 86 3.2.2. Constructive Authenticity 90 3.2.3. Projective Authenticity 97 3.3. Urban Landscape Authenticity and Sustainable Landscape-making 103 3.3.1. Authentication and Landscape Consumer Agency 103 3.3.2. Landscape Consumer Agency and the Power of Aesthetics 107 Ⅳ. CRITICAL ANALYSIS OF URBAN LANDSCAPE AUTHENTICITY IN THE POST-INDUSTRIAL URBAN CONTEXT 115 4.1. Urban Revitalization and the Post-industrial Context in South Korea 115 4.2. Two Cases: SFPA and HCV 122 4.2.1. Seoul Forest Park Alleys (SFPA) 125 4.2.2. Huinnyeoul Culture Village (HCV) 150 4.3. Summary of Landscape Authenticity Issues 178 4.3.1. On Policy: Between Preservation and Use 179 4.3.2. On Agency: Constituents of Landscape Consumers 185 4.3.3. On Landscape: Against Homogeneity 189 Ⅴ. IMPLICATIONS OF URBAN LANDSCAPE AUTHENTICITY DISCOURSE FOR THE CONTEMPORARY CITY 193 5.1. Accommodating for the Landscape Authentication Process 197 5.2. Implications of Urban Landscape Authenticity for the Landscape and Related Fields 207 Ⅵ. CONCLUSION 214 Appendix 224 A1. List of Tables 225 A2. List of Figures 226 A3. Focus Group Interview (FGI) 228 1) Methodology 230 2) Interview Questions and Results 231 Bibliography 233 Abstract in Korean 254박

Modeling The Spatiotemporal Dynamics Of Cells In The Lung

Multiple research problems related to the lung involve a need to take into account the spatiotemporal dynamics of the underlying component cells. Two such problems involve better understanding the nature of the allergic inflammatory response to explore what might cause chronic inflammatory diseases such as asthma, and determining the rules underlying stem cells used to engraft decellularized lung scaffolds in the hopes of growing new lungs for transplantation. For both problems, we model the systems computationally using agent-based modeling, a tool that enables us to capture these spatiotemporal dynamics by modeling any biological system as a collection of agents (cells) interacting with each other and within their environment. This allows to test the most important pieces of biological systems together rather than in isolation, and thus rapidly derive biological insights from resulting complex behavior that could not have been predicted beforehand, which we can then use to guide wet lab experimentation. For the allergic response, we hypothesized that stimulation of the allergic response with antigen results in a response with formal similarity to a muscle twitch or an action potential, with an inflammatory phase followed by a resolution phase that returns the system to baseline. We prepared an agent-based model (ABM) of the allergic inflammatory response and determined that antigen stimulation indeed results in a twitch-like response. To determine what might cause chronic inflammatory diseases where the twitch presumably cannot resolve back to baseline, we then tested multiple potential defects to the model. We observed that while most of these potential changes lessen the magnitude of the response but do not affect its overall behavior, extending the lifespan of activated pro-inflammatory cells such as neutrophils and eosinophil results in a prolonged inflammatory response that does not resolve to baseline. Finally, we performed a series of experiments involving continual antigen stimulation in mice, determining that there is evidence in the cytokine, cellular and physiologic (mechanical) response consistent with our hypothesis of a finite twitch and an associated refractory period. For stem cells, we made a 3-D ABM of a decellularized scaffold section seeded with a generic stem cell type. We then programmed in different sets of rules that could conceivably underlie the cell\u27s behavior, and observed the change in engraftment patterns in the scaffold over selected timepoints. We compared the change in those patterns against the change in experimental scaffold images seeded with C10 epithelial cells and mesenchymal stem cells, two cell types whose behaviors are not well understood, in order to determine which rulesets more closely match each cell type. Our model indicates that C10s are more likely to survive on regions of higher substrate while MSCs are more likely to proliferate on regions of higher substrate

Making places: performative arts practices in the city

This thesis ‘Making places: performative arts practices in the city’ results from a research project focused on a practice of placemaking informed by performative and social practice artforms. The research is concerned with grassroots arts-led interventions in the urban realm, participated in by citizens with an aim to improve the urban lived experience and to form and cultivate connections between people, place and community. This has come to be termed in the course of the research ‘social practice placemaking’ (social practice placemaking3), a practice observed in the placemaking sector as an approach that is informed by social practice arts and an attention on these arts as a means of urban revitalization. Operating at the intersection of arts, placemaking and urban theory, and place attachment thinking, the research has used a comparative approach based on participant observation and interviews at three case study sites: Art Tunnel Smithfield, Dublin, an outdoor art gallery and garden space; The Drawing Shed, London, a social arts practice predominantly operating in housing estates in Walthamstow and Wandsworth; and Big Car, Indianapolis, an arts organisation operating across the whole of this Midwest USA city. Findings are along three themes. Firstly, of the art practice and process of social practice placemaking, revealing the collaborative social practice placemaking art experience. Secondly, of urban space and place and social practice placemaking as a means of reinterpreting both spatial and cultural activities of the city. Thirdly, of place attachment and social practice placemaking and its role in and citizenship conscientisation and the politics of social practice placemaking activity in the urban public realm. The research presents an original typology of practice for the placemaking sector and examines the practice, process and role of arts in the placemaking sector and positions social practice placemaking in the social practice arts field. Significantly, the presentation of data includes the voice of the artist and non-artist protagonists. The research has various implications for the sector. Firstly, for creative and urban professionals and communities, by revealing how social practice placemaking can deepen an understanding of the relative agencies of the various modes of arts in place. Secondly, how this practice may advance placemaking practice as a whole by its use to better understand differences and similarities between placemakings within the placemaking sector, and from this, better communicate its practices to constituent stakeholders in the creative, urban design and community sectors. Thirdly, how this practice can inform the understanding of collective progressive citizenship in the urban realm and inform generative planning practices