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Sökning: WFRF:(Lynham S)

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  • Ashton, Nicholas J., et al. (författare)
  • A plasma protein classifier for predicting amyloid burden for preclinical Alzheimer's disease.
  • 2019
  • Ingår i: Science advances. - 2375-2548. ; 5:2
  • Tidskriftsartikel (refereegranskat)abstract
    • A blood-based assessment of preclinical disease would have huge potential in the enrichment of participants for Alzheimer's disease (AD) therapeutic trials. In this study, cognitively unimpaired individuals from the AIBL and KARVIAH cohorts were defined as Aβ negative or Aβ positive by positron emission tomography. Nontargeted proteomic analysis that incorporated peptide fractionation and high-resolution mass spectrometry quantified relative protein abundances in plasma samples from all participants. A protein classifier model was trained to predict Aβ-positive participants using feature selection and machine learning in AIBL and independently assessed in KARVIAH. A 12-feature model for predicting Aβ-positive participants was established and demonstrated high accuracy (testing area under the receiver operator characteristic curve = 0.891, sensitivity = 0.78, and specificity = 0.77). This extensive plasma proteomic study has unbiasedly highlighted putative and novel candidates for AD pathology that should be further validated with automated methodologies.
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  • Kumar, Abhinav, et al. (författare)
  • Enrichment of immunoregulatory proteins in the biomolecular corona of nanoparticles within human respiratory tract lining fluid
  • 2016
  • Ingår i: Nanomedicine. - 1549-9634 .- 1549-9642. ; 12:4, s. 1033-1043
  • Tidskriftsartikel (refereegranskat)abstract
    • When inhaled nanoparticles deposit in the lungs, they transit through respiratory tract lining fluid (RTLF) acquiring a biomolecular corona reflecting the interaction of the RTLF with the nanomaterial surface. Label-free snapshot proteomics was used to generate semiquantitative profiles of corona proteins formed around silica (SiO2) and poly(vinyl) acetate (PVAc) nanoparticles in RTLF, the latter employed as an archetype drug delivery vehicle. The evolved PVAc corona was significantly enriched compared to that observed on SiO2 nanoparticles (698 vs. 429 proteins identified); however both coronas contained a substantial contribution from innate immunity proteins, including surfactant protein A, napsin A and complement (C1q and C3) proteins. Functional protein classification supports the hypothesis that corona formation in RTLF constitutes opsonisation, preparing particles for phagocytosis and clearance from the lungs. These data highlight how an understanding of the evolved corona is necessary for the design of inhaled nanomedicines with acceptable safety and tailored clearance profiles. From the Clinical Editor: Inhaled nanoparticles often acquire a layer of protein corona while they go through the respiratory tract. Here, the authors investigated the identity of these proteins. The proper identification would improve the understanding of the use of inhaled nanoparticles in future therapeutics. (C) 2016 Published by Elsevier Inc.
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5.
  • Lynham, J., et al. (författare)
  • Costly stakeholder participation creates inertia in marine ecosystems
  • 2017
  • Ingår i: Marine Policy. - 0308-597X .- 1872-9460. ; 76, s. 122-129
  • Tidskriftsartikel (refereegranskat)abstract
    • Ecosystems often shift abruptly and dramatically between different regimes in response to human or natural disturbances. When ecosystems tip from one regime to another, the suite of available ecosystem benefits changes, impacting the stakeholders who rely on these benefits. These changes often create some groups who stand to incur large losses if an ecosystem returns to a previous regime. When the participation cost in the decision-making process is extremely high, this can lock in ecosystem regimes, making it harder for policy and management to shift ecosystems out of what the majority of society views as the undesirable regime. Public stakeholder meetings often have high costs of participation, thus economic theory predicts they will be dominated by extreme views and often lead to decisions that do not represent the majority viewpoint. Such extreme viewpoints can create strong inertia even when there is broad consensus to manage an ecosystem towards a different regime. In the same manner that reinforcing ecological feedback loops make it harder to exit an ecosystem regime, there are decision-making feedback loops that contribute additional inertia.
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