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Sökning: WFRF:(Brown J)

  • Resultat 2111-2120 av 2581
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2111.
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2112.
  • Björkström, Anders, 1947- (författare)
  • Regression methods in multidimensional prediction and estimation
  • 2007
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • In regression with near collinear explanatory variables, the least squares predictor has large variance. Ordinary least squares regression (OLSR) often leads to unrealistic regression coefficients. Several regularized regression methods have been proposed as alternatives. Well-known are principal components regression (PCR), ridge regression (RR) and continuum regression (CR). The latter two involve a continuous metaparameter, offering additional flexibility.For a univariate response variable, CR incorporates OLSR, PLSR, and PCR as special cases, for special values of the metaparameter. CR is also closely related to RR. However, CR can in fact yield regressors that vary discontinuously with the metaparameter. Thus, the relation between CR and RR is not always one-to-one. We develop a new class of regression methods, LSRR, essentially the same as CR, but without discontinuities, and prove that any optimization principle will yield a regressor proportional to a RR, provided only that the principle implies maximizing some function of the regressor's sample correlation coefficient and its sample variance. For a multivariate response vector we demonstrate that a number of well-established regression methods are related, in that they are special cases of basically one general procedure. We try a more general method based on this procedure, with two meta-parameters. In a simulation study we compare this method to ridge regression, multivariate PLSR and repeated univariate PLSR. For most types of data studied, all methods do approximately equally well. There are cases where RR and LSRR yield larger errors than the other methods, and we conclude that one-factor methods are not adequate for situations where more than one latent variable are needed to describe the data. Among those based on latent variables, none of the methods tried is superior to the others in any obvious way.
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2113.
  • Björstad, Åse, 1976, et al. (författare)
  • The host defense peptide LL-37 selectively permeabilizes apoptotic leukocytes.
  • 2009
  • Ingår i: Antimicrobial agents and chemotherapy. - 1098-6596. ; 53:3, s. 1027-38
  • Tidskriftsartikel (refereegranskat)abstract
    • LL-37 is a cationic host defense peptide that is highly expressed during acute inflammation and that kills bacteria by poorly defined mechanisms, resulting in permeabilization of microbial membranes. High concentrations of LL-37 have also been reported to have cytotoxic effects against eukaryotic cells, but the peptide is clearly capable of differentiating between membranes with different compositions (eukaryotic versus bacterial membranes). Eukaryotic cells such as leukocytes change their membrane composition during apoptotic cell death, when they are turned into nonfunctional but structurally intact entities. We tested whether LL-37 exerted specific activity on apoptotic cells and found that the peptide selectively permeabilized the membranes of apoptotic human leukocytes, leaving viable cells unaffected. This activity was seemingly analogous to the direct microbicidal effect of LL-37, in that it was rapid, independent of known surface receptors and/or active cell signaling, and inhibitable by serum components such as high-density lipoprotein. A similar selective permeabilization of apoptotic cells was recorded for both NK cells and neutrophils. In the latter cell type, LL-37 permeabilized both the plasma and granule membranes, resulting in the release of both lactate dehydrogenase and myeloperoxidase. Apoptosis is a way for inflammatory cells to die silently and minimize collateral tissue damage by retaining tissue-damaging and proinflammatory substances within intact membranes. Permeabilization of apoptotic leukocytes by LL-37, accompanied by the leakage of cytoplasmic as well as intragranular molecules, may thus shift the balance between pro- and anti-inflammatory signals and in this way be of importance for the termination of acute inflammation.
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2114.
  • Blythe, Jessica, et al. (författare)
  • The Dark Side of Transformation : Latent Risks in Contemporary Sustainability Discourse
  • 2018
  • Ingår i: Antipode. - : Wiley. - 0066-4812 .- 1467-8330. ; 50:5, s. 1206-1223
  • Tidskriftsartikel (refereegranskat)abstract
    • The notion of transformation is gaining traction in contemporary sustainability debates. New ways of theorising and supporting transformations are emerging and, so the argument goes, opening exciting spaces to (re)imagine and (re)structure radically different futures. Yet, questions remain about how the term is being translated from an academic concept into an assemblage of normative policies and practices, and how this process might shape social, political, and environmental change. Motivated by these questions, we identify five latent risks associated with discourse that frames transformation as apolitical and/or inevitable. We refer to these risks as the dark side of transformation. While we cannot predict the future of radical transformations towards sustainability, we suggest that scientists, policymakers, and practitioners need to consider such change in more inherently plural and political ways.
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2115.
  •  
2116.
  • Bogaert, Elke, et al. (författare)
  • Polymorphisms in the GluR2 gene are not associated with amyotrophic lateral sclerosis
  • 2012
  • Ingår i: Neurobiology of Aging. - : Elsevier BV. - 0197-4580 .- 1558-1497. ; 33:2, s. 418-420
  • Tidskriftsartikel (refereegranskat)abstract
    • Excitotoxicity is thought to play a pathogenic role in amyotrophic lateral sclerosis (ALS). Excitotoxic motor neuron death is mediated through the Ca(2+)-permeable alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)-type of glutamate receptors and Ca(2+) permeability is determined by the GluR2 subunit. We investigated whether polymorphisms or mutations in the GluR2 gene (GRIA2) predispose patients to ALS. Upon sequencing 24 patients and 24 controls no nonsynonymous coding variants were observed but 24 polymorphisms were identified, 9 of which were novel. In a screening set of 310 Belgian ALS cases and 794 healthy controls and a replication set of 3157 cases and 5397 controls from 6 additional populations no association with susceptibility, age at onset, or disease duration was observed. We conclude that polymorphisms in the GluR2 gene (GRIA2) are not a major contributory factor in the pathogenesis of ALS.
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2117.
  • Bontidean, Ibolya, et al. (författare)
  • Biosensors for detection of mercury in contaminated soils
  • 2004
  • Ingår i: Environmental Pollution. - : Elsevier BV. - 0269-7491. ; 131:2, s. 255-262
  • Tidskriftsartikel (refereegranskat)abstract
    • Biosensors based on whole bacterial cells and on bacterial heavy metal binding protein were used to determine the mercury concentration in soil. The soil samples were collected in a vegetable garden accidentally contaminated with elemental mercury 25 years earlier. Bioavailable mercury was measured using different sensors: a protein-based biosensor, a whole bacterial cell based biosensor, and a plant sensor, i.e. morphological and biochemical responses in primary leaves and roots of bean seedlings grown in the mercury-contaminated soil. For comparison the total mercury concentration of the soil samples was determined by AAS. Whole bacterial cell and protein-based biosensors gave accurate responses proportional to the total amount of mercury in the soil samples. On the contrary, plant sensors were found to be less useful indicators of soil mercury contamination, as determined by plant biomass, mercury content of primary leaves and enzyme activities. (C) 2004 Elsevier Ltd. All rights reserved.
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2118.
  •  
2119.
  • Bottero, Irene, et al. (författare)
  • Impact of landscape configuration and composition on pollinator communities across different European biogeographic regions
  • 2023
  • Ingår i: Frontiers in Ecology and Evolution. - 2296-701X. ; 11
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Heterogeneity in composition and spatial configuration of landscape elements support diversity and abundance of flower-visiting insects, but this is likely dependent on taxonomic group, spatial scale, weather and climatic conditions, and is particularly impacted by agricultural intensification. Here, we analyzed the impacts of both aspects of landscape heterogeneity and the role of climatic and weather conditions on pollinating insect communities in two economically important mass-flowering crops across Europe. Methods: Using a standardized approach, we collected data on the abundance of five insect groups (honey bees, bumble bees, other bees, hover flies and butterflies) in eight oilseed rape and eight apple orchard sites (in crops and adjacent crop margins), across eight European countries (128 sites in total) encompassing four biogeographic regions, and quantified habitat heterogeneity by calculating relevant landscape metrics for composition (proportion and diversity of land-use types) and configuration (the aggregation and isolation of land-use patches). Results: We found that flower-visiting insects responded to landscape and climate parameters in taxon- and crop-specific ways. For example, landscape diversity was positively correlated with honey bee and solitary bee abundance in oilseed rape fields, and hover fly abundance in apple orchards. In apple sites, the total abundance of all pollinators, and particularly bumble bees and solitary bees, decreased with an increasing proportion of orchards in the surrounding landscape. In oilseed rape sites, less-intensively managed habitats (i.e., woodland, grassland, meadows, and hedgerows) positively influenced all pollinators, particularly bumble bees and butterflies. Additionally, our data showed that daily and annual temperature, as well as annual precipitation and precipitation seasonality, affects the abundance of flower-visiting insects, although, again, these impacts appeared to be taxon- or crop-specific. Discussion: Thus, in the context of global change, our findings emphasize the importance of understanding the role of taxon-specific responses to both changes in land use and climate, to ensure continued delivery of pollination services to pollinator-dependent crops.
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2120.
  • Boza-Serrano, Antonio, et al. (författare)
  • Galectin-3, a novel endogenous TREM2 ligand, detrimentally regulates inflammatory response in Alzheimer’s disease
  • 2019
  • Ingår i: Acta Neuropathologica. - : Springer Science and Business Media LLC. - 0001-6322 .- 1432-0533. ; 138:2, s. 251-273
  • Tidskriftsartikel (refereegranskat)abstract
    • Alzheimer’s disease (AD) is a progressive neurodegenerative disease in which the formation of extracellular aggregates of amyloid beta (Aβ) peptide, fibrillary tangles of intraneuronal tau and microglial activation are major pathological hallmarks. One of the key molecules involved in microglial activation is galectin-3 (gal3), and we demonstrate here for the first time a key role of gal3 in AD pathology. Gal3 was highly upregulated in the brains of AD patients and 5xFAD (familial Alzheimer’s disease) mice and found specifically expressed in microglia associated with Aβ plaques. Single-nucleotide polymorphisms in the LGALS3 gene, which encodes gal3, were associated with an increased risk of AD. Gal3 deletion in 5xFAD mice attenuated microglia-associated immune responses, particularly those associated with TLR and TREM2/DAP12 signaling. In vitro data revealed that gal3 was required to fully activate microglia in response to fibrillar Aβ. Gal3 deletion decreased the Aβ burden in 5xFAD mice and improved cognitive behavior. Interestingly, a single intrahippocampal injection of gal3 along with Aβ monomers in WT mice was sufficient to induce the formation of long-lasting (2 months) insoluble Aβ aggregates, which were absent when gal3 was lacking. High-resolution microscopy (stochastic optical reconstruction microscopy) demonstrated close colocalization of gal3 and TREM2 in microglial processes, and a direct interaction was shown by a fluorescence anisotropy assay involving the gal3 carbohydrate recognition domain. Furthermore, gal3 was shown to stimulate TREM2–DAP12 signaling in a reporter cell line. Overall, our data support the view that gal3 inhibition may be a potential pharmacological approach to counteract AD.
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