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Sökning: WFRF:(Ratcliffe P.)

  • Resultat 1-36 av 36
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  • 2017
  • swepub:Mat__t
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  • Kanai, M, et al. (författare)
  • 2023
  • swepub:Mat__t
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  • Heywood, I., et al. (författare)
  • Inflation of 430-parsec bipolar radio bubbles in the Galactic Centre by an energetic event
  • 2019
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 573:7773, s. 235-237
  • Tidskriftsartikel (refereegranskat)abstract
    • The Galactic Centre contains a supermassive black hole with a mass of four million Suns1 within an environment that differs markedly from that of the Galactic disk. Although the black hole is essentially quiescent in the broader context of active galactic nuclei, X-ray observations have provided evidence for energetic outbursts from its surroundings2. Also, although the levels of star formation in the Galactic Centre have been approximately constant over the past few hundred million years, there is evidence of increased short-duration bursts3, strongly influenced by the interaction of the black hole with the enhanced gas density present within the ring-like central molecular zone4 at Galactic longitude |l| < 0.7 degrees and latitude |b| < 0.2 degrees. The inner 200-parsec region is characterized by large amounts of warm molecular gas5, a high cosmic-ray ionization rate6, unusual gas chemistry, enhanced synchrotron emission7,8, and a multitude of radio-emitting magnetized filaments9, the origin of which has not been established. Here we report radio imaging that reveals a bipolar bubble structure, with an overall span of 1 degree by 3 degrees (140 parsecs × 430 parsecs), extending above and below the Galactic plane and apparently associated with the Galactic Centre. The structure is edge-brightened and bounded, with symmetry implying creation by an energetic event in the Galactic Centre. We estimate the age of the bubbles to be a few million years, with a total energy of 7 × 1052 ergs. We postulate that the progenitor event was a major contributor to the increased cosmic-ray density in the Galactic Centre, and is in turn the principal source of the relativistic particles required to power the synchrotron emission of the radio filaments within and in the vicinity of the bubble cavities.
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  • Bardella, C., et al. (författare)
  • Expression of Idh1(R132H) in the Murine Subventricular Zone Stem Cell Niche Recapitulates Features of Early Gliomagenesis
  • 2016
  • Ingår i: Cancer Cell. - : Elsevier BV. - 1535-6108. ; 30:4, s. 578-594
  • Tidskriftsartikel (refereegranskat)abstract
    • Isocitrate dehydrogenase 1 mutations drive human gliomagenesis, probably through neomorphic enzyme activity that produces D-2-hydroxyglutarate. To model this disease, we conditionally expressed Idh1(R132H) in the subventricular zone (SVZ) of the adult mouse brain. The mice developed hydrocephalus and grossly dilated lateral ventricles, with accumulation of 2-hydroxyglutarate and reduced alpha-ketoglutarate. Stem and transit amplifying/progenitor cell populations were expanded,, and proliferation increased. Cells expressing SVZ markers infiltrated surrounding brain regions. SVZ cells also gate rise to proliferative subventricular nodules. DNA methylation was globally increased, while hydroxymethylation was decreased. Mutant SVZ cells overexpressed Wnt, cell-cycle and stem cell genes, and shared an expression signature with human gliomas. Idh1(R132H) mutation in the major adult neurogenic stem cell niche causes a phenotype resembling gliomagenesis.
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  • de Blok, W.J.G., et al. (författare)
  • an overview of the MHONGOOSE survey: Observing nearby galaxies with MeerKAT
  • 2016
  • Ingår i: Proceedings of Science. - 1824-8039.
  • Konferensbidrag (refereegranskat)abstract
    • MHONGOOSE is a deep survey of the neutral hydrogen distribution in a representative sample of 30 nearby disk and dwarf galaxies with H I masses from ∼ 106 to ∼ 1011 M, and luminosities from MR ∼ 12 to MR ∼ −22. The sample is selected to uniformly cover the available range in log(MHI). Our extremely deep observations, down to H I column density limits of well below 1018 cm−2 — or a few hundred times fainter than the typical H I disks in galaxies — will directly detect the effects of cold accretion from the intergalactic medium and the links with the cosmic web. These observations will be the first ever to probe the very low-column density neutral gas in galaxies at these high resolutions. Combination with data at other wavelengths, most of it already available, will enable accurate modeling of the properties and evolution of the mass components in these galaxies and link these with the effects of environment, dark matter distribution, and other fundamental properties such as halo mass and angular momentum. MHONGOOSE can already start addressing some of the SKA-1 science goals and will provide a comprehensive inventory of the processes driving the transformation and evolution of galaxies in the nearby universe at high resolution and over 5 orders of magnitude in column density. It will be a Nearby Galaxies Legacy Survey that will be unsurpassed until the advent of the SKA, and can serve as a highly visible, lasting statement of MeerKAT’s capabilities.
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  • Flesch, BK, et al. (författare)
  • Multicenter Study on Differential Human Neutrophil Antigen 2 Expression and Underlying Molecular Mechanisms
  • 2020
  • Ingår i: Transfusion medicine and hemotherapy : offizielles Organ der Deutschen Gesellschaft fur Transfusionsmedizin und Immunhamatologie. - : S. Karger AG. - 1660-3796. ; 47:5, s. 385-395
  • Tidskriftsartikel (refereegranskat)abstract
    • <b><i>Background:</i></b> The human neutrophil antigen 2 (HNA-2), which is expressed on CD177, is undetectable in 3–5% of the normal population. Exposure of these HNA-2<sub>null</sub> individuals to HNA-2-positive cells can cause immunization and pro­duction of HNA-2 antibodies, which can induce immune neutropenia and transfusion-related acute lung injury. In HNA-2-positive individuals, neutrophils are divided into a CD177<sup>pos.</sup> and a CD177<sup>neg.</sup> subpopulation. The molecular background of HNA-2 deficiency and the bimodal expression pattern, however, are not completely decoded. <b><i>Study Design:</i></b> An international collaboration was conducted on the genetic analysis of HNA-2-phenotyped blood samples, including HNA-2-deficient individuals, mothers, and the respective children with neonatal immune neutropenia and regular blood donors. <b><i>Results:</i></b> From a total of 54 HNA-2<sub>null</sub> individuals, 43 were homozygous for the <i>CD177</i>*<i>787A&#x3e;T</i> substitution. Six carried the <i>CD177</i>*<i>c.1291G&#x3e;A</i> single nucleotide polymorphism. All HNA-2-positive samples with &#x3e;40% CD177<sup>pos.</sup> neutrophils carried the *<i>787A</i> wild-type allele, whereas a lower rate of CD177<sup>pos.</sup> neutrophils was preferentially associated with *<i>c.787AT</i> heterozygosity. Interestingly, only the *<i>c.787A</i> allele sequence was detected in complementary DNA (cDNA) sequence analysis carried out on all *<i>c.787AT</i> heterozygous individuals. However, cDNA analysis after sorting of CD177<sup>pos.</sup> and CD177<sup>neg.</sup> neutrophil subsets from HNA-2-positive individuals showed identical sequences, which makes regulatory elements within the promoter unlikely to affect <i>CD177</i> gene transcription in different CD177 neutrophil subsets. <b><i>Conclusion:</i></b> This comprehensive study clearly demonstrates the impact of single nucleotide polymorphisms on the expression of HNA-2 on the neutrophil surface but challenges the hypothesis of regulatory epigenetic effects being implicated in the bimodal CD177 expression pattern.
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  • van der Plas, F., et al. (författare)
  • Continental mapping of forest ecosystem functions reveals a high but unrealised potential for forest multifunctionality
  • 2018
  • Ingår i: Ecology Letters. - : Wiley. - 1461-023X .- 1461-0248. ; 21:1, s. 31-42
  • Tidskriftsartikel (refereegranskat)abstract
    • Humans require multiple services from ecosystems, but it is largely unknown whether trade-offs between ecosystem functions prevent the realisation of high ecosystem multifunctionality across spatial scales. Here, we combined a comprehensive dataset (28 ecosystem functions measured on 209 forest plots) with a forest inventory dataset (105,316 plots) to extrapolate and map relationships between various ecosystem multifunctionality measures across Europe. These multifunctionality measures reflected different management objectives, related to timber production, climate regulation and biodiversity conservation/recreation. We found that trade-offs among them were rare across Europe, at both local and continental scales. This suggests a high potential for win-win' forest management strategies, where overall multifunctionality is maximised. However, across sites, multifunctionality was on average 45.8-49.8% below maximum levels and not necessarily highest in protected areas. Therefore, using one of the most comprehensive assessments so far, our study suggests a high but largely unrealised potential for management to promote multifunctional forests.
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  • Ahmad, MS, et al. (författare)
  • A patient satisfaction survey and educational package to improve the care of people hospitalised with COVID-19: a quality improvement project, Liverpool, UK
  • 2021
  • Ingår i: Wellcome open research. - : F1000 Research Ltd. - 2398-502X. ; 6, s. 222-
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The perspectives and experiences of people hospitalised with COVID-19 have been under-reported during the coronavirus pandemic. We developed and conducted a COVID-19 patient satisfaction survey in a large university-affiliated secondary healthcare centre in Liverpool, UK, during Europe’s first coronavirus wave (April-June 2020). The survey found that care was rated highly, including among people of Black Asian and Minority Ethnic (BAME) backgrounds. However, sleep-quality and communication about medications and discharge-planning were identified as areas for improvement.   Methods: To improve care for people with COVID-19 admitted to our centre, we designed an educational package for healthcare professionals working on COVID-19 wards. The package, implemented in August 2020, included healthcare worker training sessions on providing holistic care and placement of “Practice Pointers” posters. Patient satisfaction was re-evaluated during the second/third COVID-19 waves in Liverpool (September 2020 - February 2021). Results: Across waves, most (95%) respondents reported that they would recommend our hospital to friends and/or family and rated overall care highly. Comparison of the responses of second/third-wave respondents (n=101) with first-wave respondents (n=94) suggested improved patient satisfaction across most care domains but especially those related to having worries and fears addressed and being consulted about medications and their side-effects. Conclusions: People admitted with COVID-19 to our centre in Liverpool, including those from BAME backgrounds, rated the care they received highly. A simple education package improved the feedback on care received by respondents between the first and second/third waves. These UK-first findings are informing regional strategies to improve person-centred care of hospitalised people with COVID-19.
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  • Kambach, S., et al. (författare)
  • How do trees respond to species mixing in experimental compared to observational studies?
  • 2019
  • Ingår i: Ecology and Evolution. - : Wiley. - 2045-7758. ; 9:19, s. 11254-11265
  • Tidskriftsartikel (refereegranskat)abstract
    • For decades, ecologists have investigated the effects of tree species diversity on tree productivity at different scales and with different approaches ranging from observational to experimental study designs. Using data from five European national forest inventories (16,773 plots), six tree species diversity experiments (584 plots), and six networks of comparative plots (169 plots), we tested whether tree species growth responses to species mixing are consistent and therefore transferrable between those different research approaches. Our results confirm the general positive effect of tree species mixing on species growth (16% on average) but we found no consistency in species-specific responses to mixing between any of the three approaches, even after restricting comparisons to only those plots that shared similar mixtures compositions and forest types. These findings highlight the necessity to consider results from different research approaches when selecting species mixtures that should maximize positive forest biodiversity and functioning relationships.
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  • Loryan, Irena, 1977-, et al. (författare)
  • Quantitative Assessment of Drug Delivery to Tissues and Association with Phospholipidosis: A Case Study with Two Structurally Related Diamines in Development
  • 2017
  • Ingår i: Molecular Pharmaceutics. - : American Chemical Society (ACS). - 1543-8384 .- 1543-8392. ; 14:12, s. 4362-4373
  • Tidskriftsartikel (refereegranskat)abstract
    • Drug induced phospholipidosis (PLD) may be observed in the preclinical phase of drug development and pose strategic questions. As lysosomes have a central role in pathogenesis of PLD, assessment of lysosomal concentrations is important for understanding the pharmacokinetic basis of PLD manifestation and forecast of potential clinical appearance. Herein we present a systematic approach to provide insight into tissue-specific PLD by evaluation of unbound intracellular and lysosomal (reflecting acidic organelles) concentrations of two structurally related diprotic amines, GRT1 and GRT2. Their intratissue distribution was assessed using brain and lung slice assays. GRT1 induced PLD both in vitro and in vivo. GRT1 showed a high intracellular accumulation that was more pronounced in the lung, but did not cause cerebral PLD due to its effective efflux at the blood-brain barrier. Compared to GRT1, GRT2 revealed higher interstitial fluid concentrations in lung and brain, but more than 30-fold lower lysosomal trapping capacity. No signs of PLD were seen with GRT2. The different profile of GRT2 relative to GRT1 is due to a structural change resulting in a reduced basicity of one amino group. Hence, by distinct chemical modifications, undesired lysosomal trapping can be separated from desired drug delivery into different organs. In summary, assessment of intracellular unbound concentrations was instrumental in delineating the intercompound and intertissue differences in PLD induction in vivo and could be applied for identification of potential lysosomotropic compounds in drug development.
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  • Mattsson, Niklas, 1979, et al. (författare)
  • Reference measurement procedures for Alzheimer's disease cerebrospinal fluid biomarkers: definitions and approaches with focus on amyloid β42.
  • 2012
  • Ingår i: Biomarkers in medicine. - : Future Medicine Ltd. - 1752-0371 .- 1752-0363. ; 6:4, s. 409-17
  • Tidskriftsartikel (refereegranskat)abstract
    • Cerebrospinal fluid (CSF) biomarkers for Alzheimer's disease (AD) are increasingly used in clinical settings, research and drug trials. However, their broad-scale use on different technology platforms is hampered by the lack of standardization at the level of sample handling, determination of concentrations of analytes and the absence of well-defined performance criteria for in vitro diagnostic or companion diagnostic assays, which influences the apparent concentration of the analytes measured and the subsequent interpretation of the data. There is a need for harmonization of CSF AD biomarker assays that can reliably, across centers, quantitate CSF biomarkers with high analytical precision, selectivity and stability over long time periods. In this position paper, we discuss reference procedures for the measurement of CSF AD biomarkers, especially amyloid β42 and tau. We describe possible technical approaches, focusing on a selected reaction monitoring mass spectrometry assay as a candidate reference method for quantification of CSF amyloid β42.
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  • Patterson, Allison, et al. (författare)
  • Foraging range scales with colony size in high-latitude seabirds
  • 2022
  • Ingår i: Current Biology. - : Elsevier BV. - 0960-9822 .- 1879-0445. ; 32:17, s. 3800-3807
  • Tidskriftsartikel (refereegranskat)abstract
    • Density-dependent prey depletion around breeding colonies has long been considered an important factor controlling the population dynamics of colonial animals.1, 2, 3, 4 Ashmole proposed that as seabird colony size increases, intraspecific competition leads to declines in reproductive success, as breeding adults must spend more time and energy to find prey farther from the colony.1 Seabird colony size often varies over several orders of magnitude within the same species and can include millions of individuals per colony.5,6 As such, colony size likely plays an important role in determining the individual behavior of its members and how the colony interacts with the surrounding environment.6 Using tracking data from murres (Uria spp.), the world’s most densely breeding seabirds, we show that the distribution of foraging-trip distances scales to colony size0.33 during the chick-rearing stage, consistent with Ashmole’s halo theory.1,2 This pattern occurred across colonies varying in size over three orders of magnitude and distributed throughout the North Atlantic region. The strong relationship between colony size and foraging range means that the foraging areas of some colonial species can be estimated from colony sizes, which is more practical to measure over a large geographic scale. Two-thirds of the North Atlantic murre population breed at the 16 largest colonies; by extrapolating the predicted foraging ranges to sites without tracking data, we show that only two of these large colonies have significant coverage as marine protected areas. Our results are an important example of how theoretical models, in this case, Ashmole’s version of central-place-foraging theory, can be applied to inform conservation and management in colonial breeding species.
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  • Ratcliffe, S., et al. (författare)
  • Biodiversity and ecosystem functioning relations in European forests depend on environmental context
  • 2017
  • Ingår i: Ecology Letters. - : Wiley. - 1461-023X .- 1461-0248. ; 20:11, s. 1414-1426
  • Tidskriftsartikel (refereegranskat)abstract
    • The importance of biodiversity in supporting ecosystem functioning is generally well accepted. However, most evidence comes from small-scale studies, and scaling-up patterns of biodiversity-ecosystem functioning (B-EF) remains challenging, in part because the importance of environmental factors in shaping B-EF relations is poorly understood. Using a forest research platform in which 26 ecosystem functions were measured along gradients of tree species richness in six regions across Europe, we investigated the extent and the potential drivers of context dependency of B-EF relations. Despite considerable variation in species richness effects across the continent, we found a tendency for stronger B-EF relations in drier climates as well as in areas with longer growing seasons and more functionally diverse tree species. The importance of water availability in driving context dependency suggests that as water limitation increases under climate change, biodiversity may become even more important to support high levels of functioning in European forests.
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