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Sökning: WFRF:(Niven R.)

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  • Moffatt, Miriam F, et al. (författare)
  • A large-scale, consortium-based genomewide association study of asthma
  • 2010
  • Ingår i: The New England journal of medicine. - 1533-4406. ; 363:13, s. 1211-1221
  • Tidskriftsartikel (refereegranskat)abstract
    • Asthma is genetically heterogeneous. A few common alleles are associated with disease risk at all ages. Implicated genes suggest a role for communication of epithelial damage to the adaptive immune system and activation of airway inflammation. Variants at the ORMDL3/GSDMB locus are associated only with childhood-onset disease. Elevation of total serum IgE levels has a minor role in the development of asthma.
  • Schofield, James P. R., et al. (författare)
  • Stratification of asthma phenotypes by airway proteomic signatures
  • 2019
  • Ingår i: Journal of Allergy and Clinical Immunology. - Elsevier. - 0091-6749 .- 1097-6825. ; 144:1, s. 70-82
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Stratification by eosinophil and neutrophil counts increases our understanding of asthma and helps target therapy, but there is room for improvement in our accuracy in prediction of treatment responses and a need for better understanding of the underlying mechanisms. Objective: We sought to identify molecular subphenotypes of asthma defined by proteomic signatures for improved stratification. Methods: Unbiased label-free quantitative mass spectrometry and topological data analysis were used to analyze the proteomes of sputum supernatants from 246 participants (206 asthmatic patients) as a novel means of asthma stratification. Microarray analysis of sputum cells provided transcriptomics data additionally to inform on underlying mechanisms. Results: Analysis of the sputum proteome resulted in 10 clusters (ie, proteotypes) based on similarity in proteomic features, representing discrete molecular subphenotypes of asthma. Overlaying granulocyte counts onto the 10 clusters as metadata further defined 3 of these as highly eosinophilic, 3 as highly neutrophilic, and 2 as highly atopic with relatively low granulocytic inflammation. For each of these 3 phenotypes, logistic regression analysis identified candidate protein biomarkers, and matched transcriptomic data pointed to differentially activated underlying mechanisms. Conclusion: This study provides further stratification of asthma currently classified based on quantification of granulocytic inflammation and provided additional insight into their underlying mechanisms, which could become targets for novel therapies.
  • Kaiser, Eurika, et al. (författare)
  • Cluster-based reduced-order modelling of a mixing layer
  • 2014
  • Ingår i: Journal of Fluid Mechanics. - 0022-1120 .- 1469-7645. ; 754, s. 365-414
  • Tidskriftsartikel (refereegranskat)abstract
    • We propose a novel cluster-based reduced-order modelling (CROM) strategy for unsteady flows. CROM combines the cluster analysis pioneered in Gunzburger’s group (Burkardt, Gunzburger & Lee, Comput. Meth. Appl. Mech. Engng, vol. 196, 2006a, pp. 337–355) and transition matrix models introduced in fluid dynamics in Eckhardt’s group (Schneider, Eckhardt & Vollmer, Phys. Rev. E, vol. 75, 2007, art. 066313). CROM constitutes a potential alternative to POD models and generalises the Ulam–Galerkin method classically used in dynamical systems to determine a finite-rank approximation of the Perron–Frobenius operator. The proposed strategy processes a time-resolved sequence of flow snapshots in two steps. First, the snapshot data are clustered into a small number of representative states, called centroids, in the state space. These centroids partition the state space in complementary non-overlapping regions (centroidal Voronoi cells). Departing from the standard algorithm, the probabilities of the clusters are determined, and the states are sorted by analysis of the transition matrix. Second, the transitions between the states are dynamically modelled using a Markov process. Physical mechanisms are then distilled by a refined analysis of the Markov process, e.g. using finite-time Lyapunov exponent (FTLE) and entropic methods. This CROM framework is applied to the Lorenz attractor (as illustrative example), to velocity fields of the spatially evolving incompressible mixing layer and the three-dimensional turbulent wake of a bluff body. For these examples, CROM is shown to identify non-trivial quasi-attractors and transition processes in an unsupervised manner. CROM has numerous potential applications for the systematic identification of physical mechanisms of complex dynamics, for comparison of flow evolution models, for the identification of precursors to desirable and undesirable events, and for flow control applications exploiting nonlinear actuation dynamics.
  • Luederitz, Christopher, et al. (författare)
  • A review of urban ecosystem services: six key challenges for future research
  • 2015
  • Ingår i: Ecosystem Services. - Elsevier. - 2212-0416. ; 14, s. 98-112
  • Forskningsöversikt (refereegranskat)abstract
    • Global urbanization creates opportunities and challenges for humanwell-being and transition towards sustainability. Urban areas are human-environment systems that depend fundamentally on ecosystems, and thus require an understanding of the management of urban ecosystem services to ensure sustainable urban planning. The purpose of this study is to provid easy stematic review of urban ecosystem sservices research, which addresses the combined domain of ecosystem services and urban development. We examined emerging trends and gaps in how urban ecosystem services are conceptualized in peer-reviewed case study literature, including the geographical distribution ofresearch,the development and use of the urban ecosystem services concept,and thei nvolvement of stakeholders. We highlight six challenges aimed at strengthening the concept's potential to facilitate meaningful inter-and transdis ciplinary work for ecosystem services research and planning. Achieving a cohesive conceptual approach in ther esearch field will address(i)the need for more extensive spatial and contextual coverage,(ii) continual clarification of definitions, (iii)recognition of limited datat ransferability,(iv)more comprehensive stakeholder involvement,(v)more integrated research efforts,and(vi)translation of scientific findings into actionable knowledge,feeding information back into planning and management.We conclude with recommendations for conducting further research while incorporating these challenges.
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