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Sökning: WFRF:(Holden Mark A.)

  • Resultat 1-9 av 9
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2.
  • Menkveld, Albert J., et al. (författare)
  • Nonstandard Errors
  • 2024
  • Ingår i: JOURNAL OF FINANCE. - : Wiley-Blackwell. - 0022-1082 .- 1540-6261. ; 79:3, s. 2339-2390
  • Tidskriftsartikel (refereegranskat)abstract
    • In statistics, samples are drawn from a population in a data-generating process (DGP). Standard errors measure the uncertainty in estimates of population parameters. In science, evidence is generated to test hypotheses in an evidence-generating process (EGP). We claim that EGP variation across researchers adds uncertainty-nonstandard errors (NSEs). We study NSEs by letting 164 teams test the same hypotheses on the same data. NSEs turn out to be sizable, but smaller for more reproducible or higher rated research. Adding peer-review stages reduces NSEs. We further find that this type of uncertainty is underestimated by participants.
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3.
  • Heap, Graham A., et al. (författare)
  • HLA-DQA1-HLA-DRB1 variants confer susceptibility to pancreatitis induced by thiopurine immunosuppressants
  • 2014
  • Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 46:10, s. 1131-1134
  • Tidskriftsartikel (refereegranskat)abstract
    • Pancreatitis occurs in approximately 4% of patients treated with the thiopurines azathioprine or mercaptopurine. Its development is unpredictable and almost always leads to drug withdrawal. We identified patients with inflammatory bowel disease (IBD) who had developed pancreatitis within 3 months of starting these drugs from 168 sites around the world. After detailed case adjudication, we performed a genome-wide association study on 172 cases and 2,035 controls with IBD. We identified strong evidence of association within the class II HLA region, with the most significant association identified at rs2647087 (odds ratio 2.59, 95% confidence interval 2.07-3.26, P = 2 x 10(-16)). We replicated these findings in an independent set of 78 cases and 472 controls with IBD matched for drug exposure. Fine mapping of the H LA region identified association with the HLA-DQA1*02:01-HLA-DRB1*07:01 haplotype. Patients heterozygous at rs2647087 have a 9% risk of developing pancreatitis after administration of a thiopurine, whereas homozygotes have a 17% risk.
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5.
  • Hepburn, Lucy, et al. (författare)
  • A Spaetzle-like role for nerve growth factor beta in vertebrate immunity to Staphylococcus aureus
  • 2014
  • Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 346:6209, s. 641-646
  • Tidskriftsartikel (refereegranskat)abstract
    • Many key components of innate immunity to infection are shared between Drosophila and humans. However, the fly Toll ligand Spaetzle is not thought to have a vertebrate equivalent. We have found that the structurally related cystine-knot protein, nerve growth factor β (NGFβ), plays an unexpected Spaetzle-like role in immunity to Staphylococcus aureus infection in chordates. Deleterious mutations of either human NGFβ or its high-affinity receptor tropomyosin-related kinase receptor A (TRKA) were associated with severe S. aureus infections. NGFβ was released by macrophages in response to S. aureus exoproteins through activation of the NOD-like receptors NLRP3 and NLRP4 and enhanced phagocytosis and superoxide-dependent killing, stimulated proinflammatory cytokine production, and promoted calcium-dependent neutrophil recruitment. TrkA knockdown in zebrafish increased susceptibility to S. aureus infection, confirming an evolutionarily conserved role for NGFβ-TRKA signaling in pathogen-specific host immunity.
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6.
  • Brent, Rhea, et al. (författare)
  • Unstitching the Nanoscopic Mystery of Zeolite Crystal Formation
  • 2010
  • Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 0002-7863 .- 1520-5126. ; 132:39, s. 13858-13868
  • Tidskriftsartikel (refereegranskat)abstract
    • A molecular-scale understanding of crystal growth is critical to the development of important materials such as pharmaceuticals, semiconductors and catalysts. Only recently has this been possible with the advent of atomic force microscopy that permits observation of nanoscopic features on solid surfaces under a liquid or solution environment. This allows in Situ measurement of important chemical transformations such as crystal growth and dissolution. Further, the microscope can access not only an accurate height measurement of surface topography, important to deduce structural elements, but also the forces involved during nanoscopic processes. We have discovered that it is possible to use these features to "illuminate" critical nanoscopic chemical events at crystal surfaces and at the same time extract the associated energies and unstitch the details of the stepwise mechanism of growth and dissolution. This approach has been developed using nanoporous crystals of the heterogeneous catalyst zeolite L; however, in principle the approach could be adapted to many crystal growth problems.
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8.
  • Green, David C., 1987-, et al. (författare)
  • Dichroic Calcite Reveals the Pathway from Additive Binding to Occlusion
  • 2021
  • Ingår i: Crystal Growth & Design. - Washington, DC : American Chemical Society (ACS). - 1528-7483 .- 1528-7505. ; 21:7, s. 3746-3755
  • Tidskriftsartikel (refereegranskat)abstract
    • Organic additives play key roles in controlling the precipitation of calcium carbonate in the environment, industry, and biology, where they can direct polymorphism, alter crystal morphologies, and sometimes even become occluded, modifying bulk properties. However, significant questions remain regarding the pathway from adsorption on crystal surfaces to occlusion. Here, the optical properties of calcite crystals grown in the presence of the dye Congo red are used to characterize the organization of the additives within the crystal. Complemented by the analysis of surface adsorption through in situ atomic force microscopy (AFM), molecular simulations, and changes in crystal morphologies, we show that the occluded dye molecules are randomly oriented under fast growth conditions, but that slow growth engenders ordering of the dye within islands, whose orientation is determined by the dye/terrace interaction free energy. The islands are subsequently overgrown such that their internal structure is preserved. These results reveal that the occlusion of organic macromolecules into calcite can be understood by thermodynamics operating at the adsorption stage. This new insight will ultimately enable the design of additives to give specific material properties.
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9.
  • Reed, Mark S., et al. (författare)
  • The future of the uplands
  • 2009
  • Ingår i: Land use policy. - : Elsevier Limited. - 0264-8377 .- 1873-5754. ; 26:Supplement 1
  • Tidskriftsartikel (refereegranskat)abstract
    • Upland areas provide UK society with many important functions, goods and services, but have experienced a number of disturbing trends and face an uncertain future. This paper outlines historic, current and future drivers of environmental, economic, socio-cultural and policy change in UK uplands, and assesses how these have affected or are likely to affect ways in which land is used and the provision of ecosystem services. Information is synthesised into scenarios summarising a range of possible futures anticipated for UK uplands to 2060 and beyond. Finally, innovations in science, technology, governance and policy are evaluated that could enable uplands to continue providing key ecosystem services under a range of scenarios. The paper concludes that many upland areas will need to be prepared for significant reductions in grazing and prescribed burning. Conversely, other areas could experience agricultural intensification, for example significant increases in grazing or an expansion of arable or bioenergy crops into upland valleys, due to anticipated increases in global demand for food and energy. These scenarios will take place in the context of climate change. Many may take place together and may interact with each other, with complex and unpredictable implications for the upland environment, economy and society. In this context, a number of advances are needed in science, technology and policy to maintain viable uplandcommunities and the future provision of ecosystem services. These may include funding for ecological and hydrological restoration via carbon offsetting or other means. It may also involve advances in ecosystem service modelling, mapping and valuation, which through stakeholder participation could facilitate more integrated rural planning. New forms of environmental governance need to be explored that can empower those interested in developing upland economies to maintain thriving upland communities, while managing the ecosystem services they provide as efficiently as possible.
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  • Resultat 1-9 av 9

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