12 research outputs found

    Governance of planning processes in peri-urban landscapes : a comparison of three 'good examples'

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    In metropolitan areas are experiencing an increasing competition for land. Besides urbanisation, this competition is due to new societal expectations of the countryside such as space for housing, commercial activities, nature and recreational areas. As a consequence, rural spatial planning processes must attempt to balance the expectations and goals of a variety of stakeholders. Developing a well-balanced, fair and participatory rural planning process appears to be difficult. Previous research has shown that spatial planning processes often lead to resentment among the involved actors and the implementation of the planning goals often lags behind. The objective of our research is to get a better grasp of these decentralised, participatory planning processes. By getting insight into the success and failure-factors of past planning processes we hope to formulate policy guidelines for the governance of rural planning processes. Within this research, we focus on cases in which the stakeholders were satisfied with the course of the planning process. Furthermore we focus on cases in which agricultural land is lost at the expense of other functions. In the highly urbanized region of Flanders, agricultural land is vulnerable and under a continuous pressure. Within our cases we therefore focus on planning processes in which agricultural land is taken over by other functions (e.g. nature or industrial developments). Insight in the governance of such planning processes should provide guidance to policymakers and practitioners in Flanders and other countries with similar planning challenges. With this contribution we want to present the results of a first case in which agricultural land is lost in order to build a new motor-way. The majority of the involved actors indicated that they had a positive perception on the process and its outcomes. By making a qualitative analysis of a series of in-depth interviews we were able to define success factors for rural planning that exceed the particularities of the case-study

    Urban agriculture and place-making : Narratives about place and space in Ghent, Brno and Bristol

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    Despite rising enthusiasm for food growing among city dwellers, local authorities struggle to find space for urban agriculture (UA), both literally and figuratively. Consequently, UA often arises, sometimes temporarily, in marginal areas that are vulnerable to changes in planning designation. In the literature, spatial issues in relation to UA have either addressed structural questions of land use, governance and planning, or have highlighted social and personal benefits of UA. This paper aims to revisit and combine both streams of inquiry, viewing them as two co-constitutive forces that shape places through UA. The paper analyses three case studies in Brno, Ghent and Bristol, using a spatial lens that exposes important tensions as inherent characteristics of UA and conceptualises them as tensions within two space-narratives, namely abstract space and concrete place. It is suggested that UA, as a collective socio-cultural process, can transform functionally replicable spaces into unique places and thus contributes to place-making. This function should be recognised within urban planning circles, which should not only secure physical spaces to develop urban agriculture, but also create possibilities for local autonomous governance

    Urban agriculture and place-making :narratives about place and space in Ghent, Brno and Bristol

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    Despite rising enthusiasm for food growing among city dwellers, local authorities struggle to find space for urban agriculture (UA), both literally and figuratively. Consequently, UA often arises, sometimes temporarily, in marginal areas that are vulnerable to changes in planning designation. In the literature, spatial issues in relation to UA have either addressed structural questions of land use, governance and planning, or have highlighted social and personal benefits of UA. This paper aims to revisit and combine both streams of inquiry, viewing them as two co-constitutive forces that shape places through UA. The paper analyses three case studies in Brno, Ghent and Bristol, using a spatial lens that exposes important tensions as inherent characteristics of UA and conceptualises them as tensions within two space-narratives, namely abstract space and concrete place. It is suggested that UA, as a collective socio-cultural process, can transform functionally replicable spaces into unique places and thus contributes to place-making. This function should be recognised within urban planning circles, which should not only secure physical spaces to develop urban agriculture, but also create possibilities for local autonomous governance.15416

    Chromosome 11q loss and MYCN amplification demonstrate synthetic lethality with checkpoint kinase 1 inhibition in neuroblastoma

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    Neuroblastoma is the most common extracranial solid tumor found in children and despite intense multi-modal therapeutic approaches, low overall survival rates of high-risk patients persist. Tumors with heterozygous loss of chromosome 11q and MYCN amplification are two genetically distinct subsets of neuroblastoma that are associated with poor patient outcome. Using an isogenic 11q deleted model system and high-throughput drug screening, we identify checkpoint kinase 1 (CHK1) as a potential therapeutic target for 11q deleted neuroblastoma. Further investigation reveals MYCN amplification as a possible additional biomarker for CHK1 inhibition, independent of 11q loss. Overall, our study highlights the potential power of studying chromosomal aberrations to guide preclinical development of novel drug targets and combinations. Additionally, our study builds on the growing evidence that DNA damage repair and replication stress response pathways offer therapeutic vulnerabilities for the treatment of neuroblastoma

    Defects in 8-oxo-guanine repair pathway cause high frequency of C > A substitutions in neuroblastoma

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    Neuroblastomas are childhood tumors with frequent fatal relapses after induction treatment, which is related to tumor evolution with additional genomic events. Our whole-genome sequencing data analysis revealed a high frequency of somatic cytosine > adenine (C > A) substitutions in primary neuroblastoma tumors, which was associated with poor survival. We showed that increased levels of C > A substitutions correlate with copy number loss (CNL) of OGG1 or MUTYH Both genes encode DNA glycosylases that recognize 8-oxo-guanine (8-oxoG) lesions as a first step of 8-oxoG repair. Tumor organoid models with CNL of OGG1 or MUTYH show increased 8-oxoG levels compared to wild-type cells. We used CRISPR-Cas9 genome editing to create knockout clones of MUTYH and OGG1 in neuroblastoma cells. Whole-genome sequencing of single-cell OGG1 and MUTYH knockout clones identified an increased accumulation of C > A substitutions. Mutational signature analysis of these OGG1 and MUTYH knockout clones revealed enrichment for C > A signatures 18 and 36, respectively. Clustering analysis showed that the knockout clones group together with tumors containing OGG1 or MUTYH CNL. In conclusion, we demonstrate that defects in 8-oxoG repair cause accumulation of C > A substitutions in neuroblastoma, which contributes to mutagenesis and tumor evolution

    Chromosome 11q loss and MYCN amplification demonstrate synthetic lethality with checkpoint kinase 1 inhibition in neuroblastoma

    Get PDF
    Neuroblastoma is the most common extracranial solid tumor found in children and despite intense multi-modal therapeutic approaches, low overall survival rates of high-risk patients persist. Tumors with heterozygous loss of chromosome 11q and MYCN amplification are two genetically distinct subsets of neuroblastoma that are associated with poor patient outcome. Using an isogenic 11q deleted model system and high-throughput drug screening, we identify checkpoint kinase 1 (CHK1) as a potential therapeutic target for 11q deleted neuroblastoma. Further investigation reveals MYCN amplification as a possible additional biomarker for CHK1 inhibition, independent of 11q loss. Overall, our study highlights the potential power of studying chromosomal aberrations to guide preclinical development of novel drug targets and combinations. Additionally, our study builds on the growing evidence that DNA damage repair and replication stress response pathways offer therapeutic vulnerabilities for the treatment of neuroblastoma
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