593 research outputs found

    Paul Henry Gore-Booth and President F.L. Hovde

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    Photograph of President F.L. Hovde; Mr. Paul Henry Gore - Booth (British Diplomat and Author) and President Hovde, Ca. late 1940's

    Systems biology of plant molecular networks: from networks to models

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    Developmental processes are controlled by regulatory networks (GRNs), which are tightly coordinated networks of transcription factors (TFs) that activate and repress gene expression within a spatial and temporal context. In Arabidopsis thaliana, the key components and network structures of the GRNs controlling major plant reproduction processes, such as floral transition and floral organ identity specification, have been comprehensively unveiled. This thanks to advances in ‘omics’ technologies combined with genetic approaches. Yet, because of the multidimensional nature of the data and because of the complexity of the regulatory mechanisms, there is a clear need to analyse these data in such a way that we can understand how TFs control complex traits. The use of mathematical modelling facilitates the representation of the dynamics of a GRN and enables better insight into GRN complexity; while multidimensional data analysis enables the identification of properties that connect different layers from genotype-to-phenotype. Mathematical modelling and multidimensional data analysis are both parts of a systems biology approach, and this thesis presents the application of both types of systems biology approaches to flowering GRNs. Chapter 1 comprehensively reviews advances in understanding of GRNs underlying plant reproduction processes, as well as mathematical models and multidimensional data analysis approaches to study plant systems biology. As discussed in Chapter 1, an important aspect of understanding these GRNs is how perturbations in one part of the network are transmitted to other parts, and ultimately how this results in changes in phenotype. Given the complexity of recent versions of Arabidopsis GRNs - which involves highly-connected, non-linear networks of TFs, microRNAs, movable factors, hormones and chromatin modifying proteins - it is not possible to predict the effect of gene perturbations on e.g. flowering time in an intuitive way by just looking at the network structure. Therefore, mathematical modelling plays an important role in providing a quantitative understanding of GRNs. In addition, aspects of multidimensional data analysis for understanding GRNs underlying plant reproduction are also discussed in the first Chapter. This includes not only the integration of experimental data, e.g. transcriptomics with protein-DNA binding profiling, but also the integration of different types of networks identified by ‘omics’ approaches, e.g. protein-protein interaction networks and gene regulatory networks. Chapter 2 describes a mathematical model for representing the dynamics of key genes in the GRN of flowering time control. We modelled with ordinary differential equations (ODEs) the physical interactions and regulatory relationships of a set of core genes controlling Arabidopsis flowering time in order to quantitatively analyse the relationship between their expression levels and the flowering time response. We considered a core GRN composed of eight TFs: SHORT VEGETATIVE PHASE (SVP), FLOWERING LOCUS C (FLC), AGAMOUS-LIKE 24 (AGL24), SUPPRESSOR OF OVEREXPRESSION OF CONSTANS 1 (SOC1), APETALA1 (AP1), FLOWERING LOCUS T (FT), LEAFY (LFY) and FD. The connections and interactions amongst these components are justified based on experimental data, and the model is parameterised by fitting the equations to quantitative data on gene expression and flowering time. Then the model is validated with transcript data from a range of mutants. We verify that the model is able to describe some quantitative patterns seen in expression data under genetic perturbations, which supported the credibility of the model and its dynamic properties. The proposed model is able to predict the flowering time by assessing changes in the expression of the orchestrator of floral transition AP1. Overall, the work presents a framework, which allows addressing how different quantitative inputs are combined into a single quantitative output, i.e. the timing of flowering. The model allowed studying the established genetic regulations, and we discuss in Chapter 5 the steps towards using the proposed framework to zoom in and obtain new insides about the molecular mechanisms underlying the regulations. Systems biology does not only involve the use of dynamic modelling but also the development of approaches for multidimensional data analysis that are able to integrate multiple levels of systems organization. In Chapter 3, we aimed at comprehensively identifying and characterizing cis-regulatory mutations that have an effect on the GRN of flowering time control. By using ChIP-seq data and information about known DNA binding motifs of TFs involved in plant reproduction, we identified single-nucleotide polymorphisms (SNPs) that are highly discriminative in the classification of the flowering time phenotypes. Often, SNPs that overlap the position of experimentally determined binding sites (e.g. by ChIP-seq), are considered putative regulatory SNPs. We showed that regulatory SNPs are difficult to pinpoint among the sea of polymorphisms localized within binding sites determined by ChIP-seq studies. To overcome this, we narrowed the resolution by focusing on the subset of SNPs that are located within ChIP-seq peaks but that are also part of known regulatory motifs. These SNPs were used as input in a classification algorithm that could predict flowering time of Arabidopsis accessions relative to Col-0. Our strategy is able to identify SNPs that have a biological link with changes in flowering time. We then surveyed the literature to formulate hypothesis that explain the regulatory mechanism underlying the difference in phenotype conferred by a SNP. Examples include SNPs that disrupt the flowering time gene FT; in which the mutation presumably disrupts the binding region of SVP. In Chapter 5 we discuss the steps towards extending our approach to obtain a more comprehensive survey of variants that have an effect on the flowering time control. In Chapter 4, we propose a method for genome-wide prediction of protein-protein interaction (PPI) sites form the Arabidopsis interactome. Our method, named SLIDERbio, uses features encoded in the sequence of proteins and their interactions to predict PPI sites. More specifically, our method mines PPI networks to find over-represented sequence motifs in pairs of interacting proteins. In addition, the inter-species conservation of these over-represented motifs, as well as their predicted surface accessibility, are take into account to compute the likelihood of these motifs being located in a PPI site. Our results suggested that motifs overrepresented in pairs of interacting proteins that are conserved across orthologs and that have high predicted surface accessibility, are in general good putative interaction sites. We applied our method to obtain interactome-wide predictions for Arabidopsis proteins. The results were explored to formulate testable hypothesis for the molecular mechanisms underlying effects of spontaneous or induced mutagenesis on e.g. ZEITLUPE, CXIP1 and SHY2 (proteins relevant for flowering time). In addition, we showed that the binding sites are under stronger selective pressure than the overall protein sequence, and that this may be used to link sequence variability to functional divergence. Finally, Chapter 5 concludes this thesis and describes future perspectives in systems biology applied to the study of GRNs underlying plant reproduction processes. Two key directions are often followed in systems biology: 1) compiling systems-wide snapshots in which the relationships and interactions between the molecules of a system are comprehensively represented; and 2) generating accurate experimental data that can be used as input for the modelling concepts and techniques or multi-dimensional data analysis. Highlighted in Chapter 5 are the limitations in key steps within the systems biology framework applied to GRN studies. In addition, I discussed improvements and extensions that we envision for our model related to the GRN underlying the control of flowering time. Future steps for multi-dimensional data analysis are also discussed. To sum up, I discussed how to connect the different technologies developed in this thesis towards understanding the interplay between the roles of the genes, developmental stages and environmental conditions.</p

    An empirical relationship between the Deacon profile number and the Richardson number under convective conditions

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    Mean low-level temperature and wind profiles were constructed for 44 cases of free convection using the data O'Neill, Nebraska, during July and August 1956. Based upon the expression for the normalized logarithmic wind shear first suggested by Ellison and later refined by Panofsky, a theoretical formula for the Deacon number as a function of the Richardson number was derived, and values of the Deacon profile were computed. One of the parameters entering into this formula is the ration of the eddy diffusitivities for heat and momentum. This parameter was, in turn, computed from Priestley's expression for the dimensionless heat flux for free-convective cases. In using observed wind data from the mean profile in order to verify the theoretical computations of B, some marked discrepancies occurred above the 100 cm level. These were due to inconsistent wind speed readings, and it was necessary to employ control data, based on neutral profiles to correct the wind speed. When this was done, the theoretical and observed Deacon profile nurnbers were in very good agreement. The author is deeply indebted to Dr. F.L. Martin (Professor of Meteorology) for his suggestions and continued help throughout the investigations and during preparation of this paper. Special credit is due to Professor Martin for his large share in developing the derivations in this study.Approved for public release; distribution is unlimited.Captain, Republic of Indonesian Navyhttp://archive.org/details/anempiricalrelat109451210

    De stad van de toekomst wortelt in een gezonde bodem

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    De stad van de toekomst is een circulaire stad waar de toestand van de bodem cruciaal is voor de leefbaarheid en voor het succesvol doorvoeren van noodzakelijke transities. Gezien de huidige staat van de Nederlandse bodem is een gestructureerde aanpak nodig om de balans tussen boven- en ondergrond te herstellen.The city of the future is a circular city in which the condition of the soil is crucial to liveability and to the successful achievement of necessary transitions. Given the present condition of the soil in the Netherlands, a structure approach is needed to restore balance between subsurface and surface.Green Open Access added to TU Delft Institutional Repository 'You share, we take care!' - Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.Environmental Technology and Desig

    Amfibisch wonen in de delta

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    Alle signalen wijzen erop: onze manier van bouwen en wonen in de delta is op de lange termijn niet vol te houden. Onderzoeker milieutechnisch ontwerpen en universitair hoofddocent aan de TU Delft Fransje Hooimeijer pleit daarom voor een radicale herijking van het deltabeheer. Een ontwerpende, interdisciplinaire aanpak is de eerste stap om de Nederlandse delta in de toekomst veilig en leefbaar te houden. En ja, dat levert soms provocatieve ontwerpen op.Green Open Access added to TU Delft Institutional Repository 'You share, we take care!' - Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.Environmental Technology and Desig

    De boven- en ondergrond van de stad als een samenhangend systeem: The surface and subsurface of the city as a united system

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    No healthy city without a healthy surface. And yet the soil and its associated eco- and water system are a final piece in area development practice. What if we were to draw cross-sections through the above- and underground city more often and pay more attention to the 'technical space' of nature and the city below ground level? Can we achieve a more sustainable design of urban space with this?Accepted Author ManuscriptEnvironmental Technology and DesignPractice Chair Urban Area Developmen

    Rotterdam: A dynamic polder city in the Randstad

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    This chapter examines the case of Rotterdam as one of the most representative cities in the Randstad in dealing with water and adapting to the current challenges. The dynamics of the regional water system, which include groundwater and rainwater in combination with surface water in a lowland delta facing the North Sea, is crucial for the process of development and urbanisation of the Dutch polders. By creating the Waterstad area, Rotterdam took profit from its strategic position in the Randstad Delta. Van der Ham described eighth century period of time until the year 1000 as distinguished by ‘natural water management’, as nature ruled over culture. At the end of the nineteenth century, explosive urbanisation and technological prosperity put pressure on the polder cities. The manipulative era is marked by the introduction of the engine and electricity, which had an immense influence on the city and the water system.Green Open Access added to TU Delft Institutional Repository 'You share, we take care!' - Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.Environmental Technology and Desig

    Co-Create Resilience: Integrating planners, designers and engineers for adapting to flood risk in Taipei

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    Architecture and The Built EnvironmentUrbanis

    Distributed agency between 2D and 3D representation of the subsurface

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    Although severely altered, the urban subsurface is the base of the natural system, and is crucial for a stable, green, healthy, and liveable city. It is also the technical space, the engine room of the city where vital functions such as water, electricity, sewers, and drainage are located. This hybrid state needs to be recognized when designing resilient and durable (subsurface) infrastructure within urban renewal projects, so as to properly employ the parameters of both natural and technical systems. Interdisciplinary work is needed in order to be able to link natural systems (a) the water cycle, (b) soil and subsurface conditions, (c) soil improvement technology, and (d) opportunities for urban renewal (e.g. urban growth or shrinkage) in an efficient way.The importance of implementing “boundary spanning” when doing interdisciplinary work that deals with the effects of climate change is a widely recognized method, and has been an object of study in the city of Rotterdam in the past decade. The particular need for a “distributed agency” became clear during several research projects dealing with climate change, because it enables different actors to contribute to the development of the project at different phases. The representation of the city as both a natural and technical construction has been tested through the use of 2D and 3D information, which has played a significant role in enabling designs to incorporate the dimension of the subsurface. 2D and 3D information needs to anticipate different scales of specific planning and/or design phases, and they must also address various topics of the subsurface. For each phase of urban development, the distributed agency between 2D and 3D information is investigated and reflected upon. Conclusions are then drawn on the relationship between 2D and 3D information, and how it could relate in a productive, boundary spanning act that is inclusive of the subsurface. Based on these potential connections, the design of a new concept which implements boundary spanning as a facilitator is presented.Accepted Author ManuscriptEnvironmental Technology and Desig
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