32 research outputs found

    Play Among Books

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    How does coding change the way we think about architecture? Miro Roman and his AI Alice_ch3n81 develop a playful scenario in which they propose coding as the new literacy of information. They convey knowledge in the form of a project model that links the fields of architecture and information through two interwoven narrative strands in an “infinite flow” of real books

    Taken By Storm: The Rise And Fall Of Tau From Microtubule-Associated To Aggregated To Degraded

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    Tau is a microtubule-associated protein, which promotes neuronal microtubule assembly and stability. Accumulation of tau into insoluble aggregates known as neurofibrillary tangles (NFTs) is a pathological hallmark of several neurodegenerative diseases, known as tauopathies. Aggregated proteins are normally degraded by the cell’s protein degradation mechanisms, autophagy or the ubiquitin-proteasome system (UPS). In tauopathies, however, the efficiency of these degradation pathways becomes challenged by the abnormal accumulation of the tau protein, which consequently, does not get fully degraded. The current hypothesis is that small, soluble oligomeric tau species preceding NFT formation cause toxicity. However, thus far, visualizing the spatial distribution of tau monomers and oligomers inside cells under physiological or pathological conditions has not been possible. Moreover, it is unclear whether certain tau aggregate species are more resistant to degradation. Here, using single-molecule localization microscopy, we show that tau forms small oligomers on microtubules ex vivo. These oligomers are distinct from those found in cells exhibiting tau aggregation and could be precursors of aggregated tau in pathology. Furthermore, using an unsupervised shape classification algorithm that we developed, we show that different tau phosphorylation states are associated with distinct tau aggregate species. Using machine learning, we also show that autophagy and UPS target distinct classes of tau aggregates for degradation. More specifically, we propose a model where tau fibrils are targeted by UPS for degradation and NFTs are mostly degraded by autophagy, generating more tau monomers and oligomers as well as small fibrils. Our work elucidates tau’s nanoscale composition under nonaggregated and aggregated conditions ex vivo and further informs our understanding of how tau aggregates become degraded by the cell’s degradation pathways

    Microscopy Conference 2021 (MC 2021) - Proceedings

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    Das Dokument enthält die Kurzfassungen der Beiträge aller Teilnehmer an der Mikroskopiekonferenz "MC 2021"

    Suspension Near-Field Electrospinning: a Nanofabrication Method of Polymer Nanoarray Architectures for Tissue Engineering

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    Chapter 1. This chapter is divided into six sections. The first will discuss the issue of nerve tissue loss, and the strategies of therapy (1.1). The second describes the role of nanofabrication in tissue engineering (1.2). The third section details the theoretical background of electrospinning in terms of solution and process parameters (1.3). The fourth section introduces near-field electrospinning (NFES), recent advances in this field and the principles of NFES techniques (1.4). The fifth section details objectives for a tissue engineered construct for neural cell therapy, and presents possible viable solutions (1.5). The sixth summarizes the aims and structure of this thesis (1.6)..

    Optically Induced Nanostructures

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    Nanostructuring of materials is a task at the heart of many modern disciplines in mechanical engineering, as well as optics, electronics, and the life sciences. This book includes an introduction to the relevant nonlinear optical processes associated with very short laser pulses for the generation of structures far below the classical optical diffraction limit of about 200 nanometers as well as coverage of state-of-the-art technical and biomedical applications. These applications include silicon and glass wafer processing, production of nanowires, laser transfection and cell reprogramming, optical cleaning, surface treatments of implants, nanowires, 3D nanoprinting, STED lithography, friction modification, and integrated optics. The book highlights also the use of modern femtosecond laser microscopes and nanoscopes as novel nanoprocessing tools

    Towards a bio-shading system concept design methodology

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    Cities and buildings play a critical role in setting the conditions for human well-being while contributing to more just and environmentally conscious societies and economies. The design of environmentally and socially meaningful buildings has benefitted, in the past two decades, from scientific progress in the fields of computation and materials, as well as from a new way of looking into Nature as an inspirational example. This research focuses on the design of shading systems for building façades, assuming that biomimetics and computational design are a valid and proved combination. The main research question is how to develop architectural shading systems mimicking the adaptation strategies of Nature. The challenge is addressed by developing a design methodology for the creation and optimization of solar control systems based on the biological adaptive systems of terrestrial plants; creating a transfer and interpretation process of biological concepts to an architectural lexicon; and creating a universal methodology applicable to a diverse set of climatic, functional and local contexts. The research proposes a bioshading system design methodology, developed on a problem-based approach. Starting with the architectural challenge of design, solutions are sought in Nature to solve specific performance requirements of shading systems. The development of the methodology rests upon an informed process that integrates and interrelates three domains: architecture, Nature, and artifact. The ‘architecture’ domain is based on the conceptual process, the computational and parametric environmental analysis, and a diagnosis that informs the understanding of the performance requirements that need to be fulfilled. The ‘Nature’ domain is defined through an abstraction process: sustained by a mapping of plants’ features and adaptation strategies, the creation of a meme semantics triggers a performance-based design process. The ‘artifact’ domain is the physical materialization of the design concept, enabling its evaluation and emulation. The Nature-inspired design methodology developed in this research makes it possible for architects to solve the challenges of shading building façades, integrating local climate-related performance requirements with formal architectural criteria, using biomimicry as a mediator. In a step-by-step path, the user identifies specific project-related requirements, discovers and explores natural processes that guide inspiration, and conceptualizes a design proposal that is further simulated and prototyped.As cidades e os edifícios desempenham um papel crítico na definição das condições para o bem-estar humano, contribuindo para sociedades e economias mais justas e ambientalmente conscientes. O projeto de edifícios com significado ambiental e social beneficiou, nas últimas duas décadas, do progresso científico nos campos da computação e dos materiais, bem como de uma nova forma de encarar a natureza enquanto modelo inspirador. Esta investigação centra-se no design de sistemas de sombreamento para fachadas de edifícios, assumindo que a biomimética e o design computacional são uma combinação válida e comprovada. A principal questão de investigação é como desenvolver sistemas de sombreamento arquitetónicos mimetizando as estratégias de adaptação da natureza. O desafio é abordado através do desenvolvimento de uma metodologia de projeto para a criação e otimização de sistemas de controlo solar tendo por base os sistemas de adaptação biológicos das plantas vasculares terrestres; criação de um processo de transferência e interpretação de conceitos biológicos para um léxico arquitetónico; e criação uma metodologia universal aplicável a um conjunto diversificado de contextos climáticos, funcionais e locais. A presente investigação propõe uma metodologia de projeto de sistema bioshading, desenvolvida através de uma abordagem problem-based. Partindo do desafio arquitetónico de projeto, são procuradas soluções na natureza para resolver requisitos de desempenho específicos de sistemas de sombreamento. O desenvolvimento da metodologia tem por base um processo informado que integra e interrelaciona três domínios: arquitetura, Natureza e artefacto. O domínio 'arquitetura' tem por base o processo conceptual, na análise ambiental computacional e paramétrica e num diagnóstico que informa o entendimento dos requisitos de desempenho a serem cumpridos. O domínio 'Natureza' é definido por meio de um processo de abstração: sustentado por um mapeamento de recursos e estratégias de adaptação das plantas, a criação de uma semântica de memes desencadeia um processo de design com base no desempenho. O domínio "artefacto" é a materialização física do conceito de design, permitindo a sua avaliação e emulação. A metodologia de design inspirada na natureza desenvolvida neste trabalho de investigação possibilita aos arquitetos resolverem os desafios de sombreamento de fachadas de edifícios, integrando os requisitos locais de desempenho relacionados com o clima com critérios formais de arquitetura, usando a biomimética como mediadora. Num percurso progressivo evolutivo, o utilizador identifica requisitos específicos do projeto, descobre e explora processos naturais que orientam a inspiração e conceptualiza uma proposta de projeto que é simulada e prototipada

    Bio-based building skin

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    This book provides a compendium of material properties, demonstrates several successful examples of bio-based materials’ application in building facades, and offers ideas for new designs and novel solutions. It features a state-of-the-art review, addresses the latest trends in material selection, assembling systems, and innovative functions of facades in detail. Selected case studies on buildings from diverse locations are subsequently presented to demonstrate the successful implementation of various biomaterial solutions, which defines unique architectural styles and building functions. The structures, morphologies and aesthetic impressions related to bio-based building facades are discussed from the perspective of art and innovation; essential factors influencing the performance of materials with respect to functionality and safety are also presented. Special emphasis is placed on assessing the performance of a given facade throughout the service life of a building, and after its end. The book not only provides an excellent source of technical and scientific information, but also contributes to public awareness by demonstrating the benefits to be gained from the proper use of bio-based materials in facades. As such, it will appeal to a broad audience including architects, engineers, designers and building contractors. ; Presents case-studies and latest trends in material selection, assembling systems, and innovative functions of facades Discusses structure morphologies and aesthetic impressions related to bio-based building facades Highlights factors influencing performance of facades, with a special focus on service life of the buildin

    Strategies for earlier diagnosis of endometrial cancer: targeting endometrial hyperplasia

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    Endometrial cancer (EC) is the most common gynaecological malignancy in the developed world, with approximately 9000 new cases reported annually within the UK (2013-2015). Incidence rates of EC have been steadily climbing over the last decade, with a notably steep increase described in the 40 to 49-year-old age group, most likely as a consequence of rising rates of obesity. Endometrial hyperplasia (EH) is a uterine pathology which is characterised by an increase in the endometrial gland-to-stroma ratio when compared to endometrium from the proliferative phase of the menstrual cycle. The clinical significance of EH lies in its association with progression to endometrioid endometrial cancer and ‘atypical’ forms of EH are widely considered to be premalignant lesions. The overarching objective of the studies described in this thesis was to use cellular and molecular approaches to improve our capacity for earlier diagnosis of EC, through targeting and enhancing our understanding of EH. The following aims were addressed: 1. To develop a human EH tissue resource and utilise this to evaluate the current methods used to classify EH and predict its progression to EC. 2. To characterise key molecular changes within EH lesions so that they can be used to extend and enhance pathological classification of EH. 3. To explore in vitro models of the endometrium and investigate the role of PTEN and ARID1A in endometrial epithelial cell proliferation. The results obtained herein provide novel insight into the diagnostic reproducibility of the two prominent EH pathological classification systems; i) the well-known and widely used World Health Organisation 1994 (WHO94) classification and ii) the more recent Endometrioid Intraepithelial Neoplasia (EIN)/WHO2014 iteration. Following an extensive retrospective review of patient medical records, a human tissue resource was established from samples held within The Lothian NRS Human Annotated Bioresource. Archival tissue sections from n=125 individual patient samples, that were pathologically diagnosed and coded as EH lesions based on the WHO94 criteria, were identified. A dual, blinded, expert gynaecological pathologist review was subsequently carried out. Interobserver percentage agreement for each of the expert pathologists and the original WHO94 based diagnosis was 56.0 % (n=70) and 48.8 % (n=61) respectively. Upon reclassification using the EIN/WHO2014 classification system, EIN lesions were identified in 52/125 patients, with increased interobserver agreement noted between the expert pathologists (67.2 %, n=84). The EIN/WHO2014 classification system also appeared to improve upon the WHO94 system when predicting progression to EC. Investigation of EH lesions for molecular changes pertinent to endometrial carcinogenesis revealed significant differences in the immunohistochemical expression pattern of the tumour suppressor PTEN, and the transcription factors PAX2 and HAND2 between EIN and benign EH lesions. These data may, pending further validation studies, lend favourably to their use as a diagnostic pathological aid. Somewhat unexpectedly, the frequency of defects in mismatch repair protein (dMMR) expression was considerably less than hypothesised amongst EIN lesions. This was surprising given that dMMR are reported in approximately 25-30 % of somatic ECs. An accepted risk factor for the development of both EH and EC is exposure to ‘unopposed oestrogens’ i.e. oestrogen without progesterone opposition. A novel in vitro model was created utilising EC cell lines to investigate the proliferative effects of silencing two commonly mutated genes within both EHs and ECs, namely PTEN and ARID1A, and also the overexpression of oestrogen receptor alpha (ERα). Cellular manipulation of gene expression for ERα, PTEN and ARID1A was performed. Findings demonstrated a significant increase in EC cell proliferation with knockdown of PTEN and to a lesser extent ARID1A, when compared to EC cells transfected with a scrambled sequence. The addition of a functional ERɑ to the knockdown models did not appear to increase cell proliferation in this context. In conclusion, novel data described herein highlights the current difficulties in achieving a reproducible diagnosis for EH. The use of immunohistochemistry identified changes in protein expression, which together with automated tissue analysis and in vitro studies, were used to complement and extend our understanding of premalignant changes in the endometrium. These findings have implications for the clinical management of women diagnosed with EH, as well as the development of a personalised approach to monitoring of women at increased risk of progression to EC
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