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Sökning: WFRF:(Flynn Michael J.)

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1.
  • Craddock, Nick, et al. (författare)
  • Genome-wide association study of CNVs in 16,000 cases of eight common diseases and 3,000 shared controls
  • 2010
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 464:7289, s. 713-720
  • Tidskriftsartikel (refereegranskat)abstract
    • Copy number variants (CNVs) account for a major proportion of human genetic polymorphism and have been predicted to have an important role in genetic susceptibility to common disease. To address this we undertook a large, direct genome-wide study of association between CNVs and eight common human diseases. Using a purpose-designed array we typed,19,000 individuals into distinct copy-number classes at 3,432 polymorphic CNVs, including an estimated similar to 50% of all common CNVs larger than 500 base pairs. We identified several biological artefacts that lead to false-positive associations, including systematic CNV differences between DNAs derived from blood and cell lines. Association testing and follow-up replication analyses confirmed three loci where CNVs were associated with disease-IRGM for Crohn's disease, HLA for Crohn's disease, rheumatoid arthritis and type 1 diabetes, and TSPAN8 for type 2 diabetes-although in each case the locus had previously been identified in single nucleotide polymorphism (SNP)-based studies, reflecting our observation that most common CNVs that are well-typed on our array are well tagged by SNPs and so have been indirectly explored through SNP studies. We conclude that common CNVs that can be typed on existing platforms are unlikely to contribute greatly to the genetic basis of common human diseases.
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2.
  • Kattge, Jens, et al. (författare)
  • TRY plant trait database - enhanced coverage and open access
  • 2020
  • Ingår i: Global Change Biology. - : Wiley-Blackwell. - 1354-1013 .- 1365-2486. ; 26:1, s. 119-188
  • Tidskriftsartikel (refereegranskat)abstract
    • Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives.
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3.
  • Bellm, Eric C., et al. (författare)
  • The Zwicky Transient Facility : System Overview, Performance, and First Results
  • 2019
  • Ingår i: Publications of the Astronomical Society of the Pacific. - : IOP Publishing. - 0004-6280 .- 1538-3873. ; 131:995
  • Tidskriftsartikel (refereegranskat)abstract
    • The Zwicky Transient Facility (ZTF) is a new optical time-domain survey that uses the Palomar 48 inch Schmidt telescope. A custom-built wide-field camera provides a 47 deg(2) field of view and 8 s readout time, yielding more than an order of magnitude improvement in survey speed relative to its predecessor survey, the Palomar Transient Factory. We describe the design and implementation of the camera and observing system. The ZTF data system at the Infrared Processing and Analysis Center provides near-real-time reduction to identify moving and varying objects. We outline the analysis pipelines, data products, and associated archive. Finally, we present on-sky performance analysis and first scientific results from commissioning and the early survey. ZTF's public alert stream will serve as a useful precursor for that of the Large Synoptic Survey Telescope.
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5.
  • Rich, Rebecca L., et al. (författare)
  • A global benchmark study using affinity-based biosensors
  • 2009
  • Ingår i: Analytical Biochemistry. - : Elsevier BV. - 0003-2697 .- 1096-0309. ; 386:2, s. 194-216
  • Tidskriftsartikel (refereegranskat)abstract
    • To explore the variability in biosensor studies, 150 participants from 20 countries were given the same protein samples and asked to determine kinetic rate constants for the interaction. We chose a protein system that was amenable to analysis using different biosensor platforms as well as by users of different expertise levels. The two proteins (a 50-kDa Fab and a 60-kDa glutathione S-transferase [GST] antigen) form a relatively high-affinity complex, so participants needed to optimize several experimental parameters, including ligand immobilization and regeneration conditions as well as analyte concentrations and injection/dissociation times. Although most participants collected binding responses that could be fit to yield kinetic parameters, the quality of a few data sets could have been improved by optimizing the assay design. Once these outliers were removed, the average reported affinity across the remaining panel of participants was 620 pM with a standard deviation of 980 pM. These results demonstrate that when this biosensor assay was designed and executed appropriately, the reported rate constants were consistent, and independent of which protein was immobilized and which biosensor was used.
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6.
  • Farnocchia, Davide, et al. (författare)
  • International Asteroid Warning Network Timing Campaign: 2019 XS
  • 2022
  • Ingår i: The Planetary Science Journal. - : Institute of Physics Publishing (IOPP). - 2632-3338. ; 3:7
  • Tidskriftsartikel (refereegranskat)abstract
    • As part of the International Asteroid Warning Network's observational exercises, we conducted a campaign to observe near-Earth asteroid 2019 XS around its close approach to Earth on 2021 November 9. The goal of the campaign was to characterize errors in the observation times reported to the Minor Planet Center, which become an increasingly important consideration as astrometric accuracy improves and more fast-moving asteroids are observed. As part of the exercise, a total of 957 astrometric observations of 2019 XS during the encounter were reported and subsequently were analyzed to obtain the corresponding residuals. While the timing errors are typically smaller than 1 s, the reported times appear to be negatively biased, i.e., they are generally earlier than they should be. We also compared the observer-provided position uncertainty with the cross-track residuals, which are independent of timing errors. A large fraction of the estimated uncertainties appear to be optimistic, especially when <0 2. We compiled individual reports for each observer to help identify and remove the root cause of any possible timing error and improve the uncertainty quantification process. We suggest possible sources of timing errors and describe a simple procedure to derive reliable, conservative position uncertainties.
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7.
  • Guo, Hao, et al. (författare)
  • Heterogeneity and chemical reactivity of the remote troposphere defined by aircraft measurements
  • 2021
  • Ingår i: Atmospheric Chemistry And Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 21:18, s. 13729-13746
  • Tidskriftsartikel (refereegranskat)abstract
    • The NASA Atmospheric Tomography (ATom) mission built a photochemical climatology of air parcels based on in situ measurements with the NASA DC-8 aircraft along objectively planned profiling transects through the middle of the Pacific and Atlantic oceans. In this paper we present and analyze a data set of 10 s (21(m) merged and gap-filled observations of the key reactive species driving the chemical budgets of O-3 and CH4 (O-3, CH4, CO, H2O, HCHO, H2O2, CH3OOH, C2H6, higher alkanes, alkenes, aromatics, NOx, HNO3, HNO4, peroxyacetyl nitrate, other organic nitrates), consisting of 146 494 distinct air parcels from ATom deployments 1 through 4. Six models calculated the O-3 and CH4 photochemical tendencies from this modeling data stream for ATom 1. We find that 80 %-90 % of the total reactivity lies in the top 50 % of the parcels and 25 %-35 % in the top 10 %, supporting previous model-only studies that tropospheric chemistry is driven by a fraction of all the air. In other words, accurate simulation of the least reactive 50 % of the troposphere is unimportant for global budgets. Surprisingly, the probability densities of species and reactivities averaged on a model scale (100 km) differ only slightly from the 2 km ATom data, indicating that much of the heterogeneity in tropospheric chemistry can be captured with current global chemistry models. Comparing the ATom reactivities over the tropical oceans with climatological statistics from six global chemistry models, we find excellent agreement with the loss of O-3 and CH4 but sharp disagreement with production of O-3. The models sharply underestimate O-3 production below 4 km in both Pacific and Atlantic basins, and this can be traced to lower NOx levels than observed. Attaching photochemical reactivities to measurements of chemical species allows for a richer, yet more constrained-towhat-matters, set of metrics for model evaluation.
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8.
  • Guo, Hao, et al. (författare)
  • Heterogeneity and chemical reactivity of the remote troposphere defined by aircraft measurements – corrected
  • 2023
  • Ingår i: Atmospheric Chemistry And Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 23:1, s. 99-117
  • Tidskriftsartikel (refereegranskat)abstract
    • The NASA Atmospheric Tomography (ATom) mission built a photochemical climatology of air parcels based on in situ measurements with the NASA DC-8 aircraft along objectively planned profiling transects through the middle of the Pacific and Atlantic oceans. In this paper we present and analyze a data set of 10 s (2 km) merged and gap-filled observations of the key reactive species driving the chemical budgets of O3 and CH4 (O3, CH4, CO, H2O, HCHO, H2O2, CH3OOH, C2H6, higher alkanes, alkenes, aromatics, NOx, HNO3, HNO4, peroxyacetyl nitrate, and other organic nitrates), consisting of 146 494 distinct air parcels from ATom deployments 1 through 4. Six models calculated the O3 and CH4 photochemical tendencies from this modeling data stream for ATom 1. We find that 80 %–90 % of the total reactivity lies in the top 50 % of the parcels and 25 %–35 % in the top 10 %, supporting previous model-only studies that tropospheric chemistry is driven by a fraction of all the air. Surprisingly, the probability densities of species and reactivities averaged on a model scale (100 km) differ only slightly from the 2 km ATom 10 s data, indicating that much of the heterogeneity in tropospheric chemistry can be captured with current global chemistry models. Comparing the ATom reactivities over the tropical oceans with climatological statistics from six global chemistry models, we find generally good agreement with the reactivity rates for O3 and CH4. Models distinctly underestimate O3 production below 2 km relative to the mid-troposphere, and this can be traced to lower NOx levels than observed. Attaching photochemical reactivities to measurements of chemical species allows for a richer, yet more constrained-to-what-matters, set of metrics for model evaluation.
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9.
  • Farnocchia, Davide, et al. (författare)
  • The Second International Asteroid Warning Network Timing Campaign: 2005 LW3
  • 2023
  • Ingår i: The Planetary Science Journal. - : Institute of Physics (IOP). - 2632-3338. ; 4:11
  • Tidskriftsartikel (refereegranskat)abstract
    • The Earth close approach of near-Earth asteroid 2005 LW3 on 2022 November 23 represented a good opportunity for a second observing campaign to test the timing accuracy of astrometric observation. With 82 participating stations, the International Asteroid Warning Network collected 1046 observations of 2005 LW3 around the time of the close approach. Compared to the previous timing campaign targeting 2019 XS, some individual observers were able to significantly improve the accuracy of their reported observation times. In particular, U.S. surveys achieved good timing performance. However, no broad, systematic improvement was achieved compared to the previous campaign, with an overall negative bias persisting among the different observers. The calibration of observing times and the mitigation of timing errors should be important future considerations for observers and orbit computers, respectively.
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10.
  • Bird, Lori, et al. (författare)
  • Wind and solar energy curtailment : A review of international experience
  • 2016
  • Ingår i: Renewable & sustainable energy reviews. - : Elsevier. - 1364-0321 .- 1879-0690. ; 65, s. 577-586
  • Forskningsöversikt (refereegranskat)abstract
    • Greater penetrations of variable renewable generation on some electric grids have resulted in increased levels of curtailment in recent years. Studies of renewable energy grid integration have found that curtailment levels may grow as the penetration of wind and solar energy generation increases. This paper reviews international experience with curtailment of wind and solar energy on bulk power systems in recent years, with a focus on eleven countries in Europe, North America, and Asia. It examines levels of curtailment, the causes of curtailment, curtailment methods and use of market based dispatch, as well as operational, institutional, and other changes that are being made to reduce renewable energy curtailment.
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11.
  • Flynn, Michael J., et al. (författare)
  • Modelling cloud processing of aerosol during the ACE-2 HILLCLOUD experiment
  • 2000
  • Ingår i: Tellus. Series B: Chemical and Physical Meteorology. - : Stockholm University Press. - 0280-6509. ; 52:2, s. 779-800
  • Tidskriftsartikel (refereegranskat)abstract
    • A numerical model has been used to simulate the conditions observed during the ACE-2 Hillcloud experiment and to study the processes which may be taking place. The model incorporates gas phase chemistry of sulphur and nitrogen compounds upstream of the cloud, and the interaction of aerosol, precursor trace gases and oxidants within the cloud. Gas phase and aerosol inputs to the model have been provided from measurements made in the field. Dynamics of the air flow over the hill consisted of simple prescribed dynamics based on wind speed measurements, and also for some cases modelled dynamics. In this modelling study, it was found that during clean case studies particles down to 40-55 nm diameter were activated to form cloud droplets, the total number of droplets formed ranging from 200 to 400 drops/cm3. Significant modification of the aerosol spectra due to cloud processing was observed. In polluted cases particles down to 65-80 nm diameter were activated to form cloud droplets, the total number of droplets ranging from 800 to 2800 drops/cm3. Modification of the aerosol spectra due to cloud processing was slight. In all cases, changes in the aerosol spectra were due to both the uptake of HNO3, HCl, NH3 and SO2 from the gas phase, (the SO2 being oxidised to sulphate) and the repartitioning of species such as HNO3, HCl, and NH3 from larger particles onto smaller ones. Modelling results have been compared with observations made. Modelled droplet numbers are typically within 20% of the best measured values. The mode of the droplet distribution typically around 10-20 μm for clean cases and 4-8 μm for polluted cases was found to be in good agreement with the measured values of 10-25 μm for clean cases, but not in such good agreement for polluted cases. Measurements of upwind and interstitial aerosol distributions showed that the smallest particles activated were 30 and 50 nm for clean and polluted cases respectively, slightly smaller than the model values quoted above. Measured upwind and downwind aerosol spectra showed similar modification to that predicted by the model in eight out of the eleven model runs carried out. Chemistry measurements also give general evidence for both the uptake of species from the gas phase, and repartitioning of species from large particles onto smaller ones, though comparisons for individual cases are more difficult. From this modelling study, it can be concluded that in general, in the remote environment the exchange of hydrochloric acid, nitric acid and ammonia between aerosol particles and take up from the gas phase in the vicinity of cloud may be a very important mechanism in regulating the evolution of the aerosol spectrum. Further, the much more linear relationship between cloud droplet and accumulation mode aerosol number, which was observed in the measurements made during the ACE-2 HILLCLOUD project is supported by these modelling results. The implications of this for the indirect effect will be explored in future work.
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12.
  • Swartling, Fredrik Johansson, et al. (författare)
  • Pleiotropic role for MYCN in medulloblastoma
  • 2010
  • Ingår i: Genes & Development. - : Cold Spring Harbor Laboratory. - 0890-9369 .- 1549-5477. ; 24:10, s. 1059-1072
  • Tidskriftsartikel (refereegranskat)abstract
    • Medulloblastoma (MB) is the most common malignant brain tumor of childhood. Sonic Hedgehog (SHH) signaling drives a minority of MB, correlating with desmoplastic pathology and favorable outcome. The majority, however, arises independently of SHH and displays classic or large cell anaplastic (LCA) pathology and poor prognosis. To identify common signaling abnormalities, we profiled mRNA, demonstrating misexpression of MYCN in the majority of human MB and negligible expression in normal cerebella. We clarified a role in pathogenesis by targeting MYCN (and luciferase) to cerebella of transgenic mice. MYCN-driven MB showed either classic or LCA pathologies, with Shh signaling activated in approximately 5% of tumors, demonstrating that MYCN can drive MB independently of Shh. MB arose at high penetrance, consistent with a role for MYCN in initiation. Tumor burden correlated with bioluminescence, with rare metastatic spread to the leptomeninges, suggesting roles for MYCN in both progression and metastasis. Transient pharmacological down-regulation of MYCN led to both clearance and senescence of tumor cells, and improved survival. Targeted expression of MYCN thus contributes to initiation, progression, and maintenance of MB, suggesting a central role for MYCN in pathogenesis.
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