| 1. |
- Brownstein, Catherine A., et al.
(författare)
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An international effort towards developing standards for best practices in analysis, interpretation and reporting of clinical genome sequencing results in the CLARITY Challenge
- 2014
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Ingår i: Genome Biology. - : Springer Science and Business Media LLC. - 1465-6906 .- 1474-760X. ; 15:3, s. R53-
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Tidskriftsartikel (refereegranskat)abstract
- Background: There is tremendous potential for genome sequencing to improve clinical diagnosis and care once it becomes routinely accessible, but this will require formalizing research methods into clinical best practices in the areas of sequence data generation, analysis, interpretation and reporting. The CLARITY Challenge was designed to spur convergence in methods for diagnosing genetic disease starting from clinical case history and genome sequencing data. DNA samples were obtained from three families with heritable genetic disorders and genomic sequence data were donated by sequencing platform vendors. The challenge was to analyze and interpret these data with the goals of identifying disease-causing variants and reporting the findings in a clinically useful format. Participating contestant groups were solicited broadly, and an independent panel of judges evaluated their performance. Results: A total of 30 international groups were engaged. The entries reveal a general convergence of practices on most elements of the analysis and interpretation process. However, even given this commonality of approach, only two groups identified the consensus candidate variants in all disease cases, demonstrating a need for consistent fine-tuning of the generally accepted methods. There was greater diversity of the final clinical report content and in the patient consenting process, demonstrating that these areas require additional exploration and standardization. Conclusions: The CLARITY Challenge provides a comprehensive assessment of current practices for using genome sequencing to diagnose and report genetic diseases. There is remarkable convergence in bioinformatic techniques, but medical interpretation and reporting are areas that require further development by many groups.
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| 2. |
- Kalra, Hina, et al.
(författare)
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Vesiclepedia : a compendium for extracellular vesicles with continuous community annotation
- 2012
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Ingår i: PLoS biology. - : Public library of science. - 1544-9173 .- 1545-7885. ; 10:12, s. e1001450-
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Tidskriftsartikel (refereegranskat)abstract
- Extracellular vesicles (EVs) are membraneous vesicles released by a variety of cells into their microenvironment. Recent studies have elucidated the role of EVs in intercellular communication, pathogenesis, drug, vaccine and gene-vector delivery, and as possible reservoirs of biomarkers. These findings have generated immense interest, along with an exponential increase in molecular data pertaining to EVs. Here, we describe Vesiclepedia, a manually curated compendium of molecular data (lipid, RNA, and protein) identified in different classes of EVs from more than 300 independent studies published over the past several years. Even though databases are indispensable resources for the scientific community, recent studies have shown that more than 50% of the databases are not regularly updated. In addition, more than 20% of the database links are inactive. To prevent such database and link decay, we have initiated a continuous community annotation project with the active involvement of EV researchers. The EV research community can set a gold standard in data sharing with Vesiclepedia, which could evolve as a primary resource for the field.
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| 3. |
- Kirkevag, A., et al.
(författare)
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Aerosol-climate interactions in the Norwegian Earth System Model-NorESM1-M
- 2013
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Ingår i: Geoscientific Model Development. - : Copernicus GmbH. - 1991-959X .- 1991-9603. ; 6:1, s. 207-244
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Tidskriftsartikel (refereegranskat)abstract
- The objective of this study is to document and evaluate recent changes and updates to the module for aerosols and aerosol-cloud-radiation interactions in the atmospheric module CAM4-Oslo of the core version of the Norwegian Earth System Model (NorESM), NorESM1-M. Particular attention is paid to the role of natural organics, sea salt, and mineral dust in determining the gross aerosol properties as well as the anthropogenic contribution to these properties and the associated direct and indirect radiative forcing. The aerosol module is extended from earlier versions that have been published, and includes life-cycling of sea salt, mineral dust, particulate sulphate, black carbon, and primary and secondary organics. The impacts of most of the numerous changes since previous versions are thoroughly explored by sensitivity experiments. The most important changes are: modified prognostic sea salt emissions; updated treatment of precipitation scavenging and gravitational settling; inclusion of biogenic primary organics and methane sulphonic acid (MSA) from oceans; almost doubled production of land-based biogenic secondary organic aerosols (SOA); and increased ratio of organic matter to organic carbon (OM/OC) for biomass burning aerosols from 1.4 to 2.6. Compared with in situ measurements and remotely sensed data, the new treatments of sea salt and dust aerosols give smaller biases in near-surface mass concentrations and aerosol optical depth than in the earlier model version. The model biases for mass concentrations are approximately unchanged for sulphate and BC. The enhanced levels of modeled OM yield improved overall statistics, even though OM is still underestimated in Europe and overestimated in North America. The global anthropogenic aerosol direct radiative forcing (DRF) at the top of the atmosphere has changed from a small positive value to -0.08 W m(-2) in CAM4-Oslo. The sensitivity tests suggest that this change can be attributed to the new treatment of biomass burning aerosols and gravitational settling. Although it has not been a goal in this study, the new DRF estimate is closer both to the median model estimate from the AeroCom intercomparison and the best estimate in IPCC AR4. Estimated DRF at the ground surface has increased by ca. 60 %, to -1.89 W m(-2). We show that this can be explained by new emission data and omitted mixing of constituents between updrafts and downdrafts in convective clouds. The increased abundance of natural OM and the introduction of a cloud droplet spectral dispersion formulation are the most important contributions to a considerably decreased estimate of the indirect radiative forcing (IndRF). The IndRF is also found to be sensitive to assumptions about the coating of insoluble aerosols by sulphate and OM. The IndRF of -1.2 W m(-2), which is closer to the IPCC AR4 estimates than the previous estimate of -1.9 W m(-2), has thus been obtained without imposing unrealistic artificial lower bounds on cloud droplet number concentrations.
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| 4. |
- Mårtensson, E. Monica, et al.
(författare)
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The role of sea-salt emissions in controlling the marine Aitken and accumulation mode aerosol : a model study
- 2010
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Ingår i: Tellus. Series B, Chemical and physical meteorology. - : Stockholm University Press. - 0280-6509 .- 1600-0889. ; 62:4, s. 259-279
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Tidskriftsartikel (refereegranskat)abstract
- The remote marine aerosol and the cloud droplet number concentration (CDNC) are examined with an aerosol microphysics box model in an attempt to better understand the processes involved in the formation and transformation of the marine aerosol. Emission of submicrometre sea-salt and dimethylsulfide (DMS) have been included together with aerosol dynamics, gas and liquid phase chemistry and cloud processing representative for the marine boundary layer atmosphere. Our simulations are able to reproduce a bimodal submicrometre size distribution with realistic number concentrations even when new particle formation by nucleation is neglected. This indicates that ultrafine primary sea-salt flux is an important source of Aitken mode particles and CDNC. However, sulphate still constitutes 20-80% of the Aitken and accumulation mode masses. The temperature dependence of the sea-salt source function leads to a 23% decrease in total number concentration when the temperature increases from 12 to 20 degrees C. The influence of DMS emission on the aerosol and CDNC is minimal but the size distribution and mass concentration of sulphate is changed, mostly due to in-cloud processes. The wind speed is the dominant factor determining the CDNC, although entrainment of aerosols from free troposphere can have a substantial effect.
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| 5. |
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| 6. |
- Salter, Matthew E., et al.
(författare)
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On the seawater temperature dependence of the sea spray aerosol generated by a continuous plunging jet
- 2014
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Ingår i: Journal of Geophysical Research - Atmospheres. - 2169-897X .- 2169-8996. ; 119:14, s. 9052-9072
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Tidskriftsartikel (refereegranskat)abstract
- Breaking waves on the ocean surface produce bubbles which, upon bursting, deliver seawater constituents into the atmosphere as sea spray aerosol particles. One way of investigating this process in the laboratory is to generate a bubble plume by a continuous plunging jet. We performed a series of laboratory experiments to elucidate the role of seawater temperature on aerosol production from artificial seawater free from organic contamination using a plunging jet. The seawater temperature was varied from -1.3 degrees C to 30.1 degrees C, while the volume of air entrained by the jet, surface bubble size distributions, and size distribution of the aerosol particles produced was monitored. We observed that the volume of air entrained decreased as the seawater temperature was increased. The number of surface bubbles with film radius smaller than 2 mm decreased nonlinearly with seawater temperature. This decrease was coincident with a substantial reduction in particle production. The number concentrations of particles with dry diameter less than similar to 1 mu m decreased substantially as the seawater temperature was increased from -1.3 degrees C to similar to 9 degrees C. With further increase in seawater temperature (up to 30 degrees C), a small increase in the number concentration of larger particles (dry diameter >similar to 0.3 mu m) was observed. Based on these observations, we infer that as seawater temperature increases, the process of bubble fragmentation changes, resulting in decreased air entrainment by the plunging jet, as well as the number of bubbles with film radius smaller than 2 mm. This again results in decreased particle production with increasing seawater temperature.
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| 7. |
- Schoch, CL, et al.
(författare)
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Nuclear ribosomal internal transcribed spacer (ITS) region as a universal DNA barcode marker for Fungi
- 2012
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490. ; 109:16, s. 6241-6246
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Tidskriftsartikel (refereegranskat)abstract
- Six DNA regions were evaluated as potential DNA barcodes for Fungi, the second largest kingdom of eukaryotic life, by a multinational, multilaboratory consortium. The region of the mitochondrial cytochrome c oxidase subunit 1 used as the animal barcode was excluded as a potential marker, because it is difficult to amplify in fungi, often includes large introns, and can be insufficiently variable. Three subunits from the nuclear ribosomal RNA cistron were compared together with regions of three representative protein-coding genes (largest subunit of RNA polymerase II, second largest subunit of RNA polymerase II, and minichromosome maintenance protein). Although the protein-coding gene regions often had a higher percent of correct identification compared with ribosomal markers, low PCR amplification and sequencing success eliminated them as candidates for a universal fungal barcode. Among the regions of the ribosomal cistron, the internal transcribed spacer (ITS) region has the highest probability of successful identification for the broadest range of fungi, with the most clearly defined barcode gap between inter- and intraspecific variation. The nuclear ribosomal large subunit, a popular phylogenetic marker in certain groups, had superior species resolution in some taxonomic groups, such as the early diverging lineages and the ascomycete yeasts, but was otherwise slightly inferior to the ITS. The nuclear ribosomal small subunit has poor species-level resolution in fungi. ITS will be formally proposed for adoption as the primary fungal barcode marker to the Consortium for the Barcode of Life, with the possibility that supplementary barcodes may be developed for particular narrowly circumscribed taxonomic groups.
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| 8. |
- Zábori, Julia, et al.
(författare)
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Wintertime Arctic Ocean sea water properties and primary marine aerosol concentrations
- 2012
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Ingår i: Atmospheric Chemistry And Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 12:21, s. 10405-10421
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Tidskriftsartikel (refereegranskat)abstract
- Sea spray aerosols are an important part of the climate system through their direct and indirect effects. Due to the diminishing sea ice, the Arctic Ocean is one of the most rapidly changing sea spray aerosol source areas. However, the influence of these changes on primary particle production is not known. In laboratory experiments we examined the influence of Arctic Ocean water temperature, salinity, and oxygen saturation on primary particle concentration characteristics. Sea water temperature was identified as the most important of these parameters. A strong decrease in sea spray aerosol production with increasing water temperature was observed for water temperatures between -1 degrees C and 9 degrees C. Aerosol number concentrations decreased from at least 1400 cm(-3) to 350 cm-3. In general, the aerosol number size distribution exhibited a robust shape with one mode close to dry diameter D-p 0.2 mu m with approximately 45% of particles at smaller sizes. Changes in sea water temperature did not result in pronounced change of the shape of the aerosol size distribution, only in the magnitude of the concentrations. Our experiments indicate that changes in aerosol emissions are most likely linked to changes of the physical properties of sea water at low temperatures. The observed strong dependence of sea spray aerosol concentrations on sea water temperature, with a large fraction of the emitted particles in the typical cloud condensation nuclei size range, provide strong arguments for a more careful consideration of this effect in climate models.
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| 9. |
- Hsu, Yi-Hsiang, et al.
(författare)
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An Integration of Genome-Wide Association Study and Gene Expression Profiling to Prioritize the Discovery of Novel Susceptibility Loci for Osteoporosis-Related Traits
- 2010
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Ingår i: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 6:6, s. e1000977-
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Tidskriftsartikel (refereegranskat)abstract
- Osteoporosis is a complex disorder and commonly leads to fractures in elderly persons. Genome-wide association studies (GWAS) have become an unbiased approach to identify variations in the genome that potentially affect health. However, the genetic variants identified so far only explain a small proportion of the heritability for complex traits. Due to the modest genetic effect size and inadequate power, true association signals may not be revealed based on a stringent genome-wide significance threshold. Here, we take advantage of SNP and transcript arrays and integrate GWAS and expression signature profiling relevant to the skeletal system in cellular and animal models to prioritize the discovery of novel candidate genes for osteoporosis-related traits, including bone mineral density (BMD) at the lumbar spine (LS) and femoral neck (FN), as well as geometric indices of the hip (femoral neck-shaft angle, NSA; femoral neck length, NL; and narrow-neck width, NW). A two-stage meta-analysis of GWAS from 7,633 Caucasian women and 3,657 men, revealed three novel loci associated with osteoporosis-related traits, including chromosome 1p13.2 (RAP1A, p = 3.6 x 10(-8)), 2q11.2 (TBC1D8), and 18q11.2 (OSBPL1A), and confirmed a previously reported region near TNFRSF11B/OPG gene. We also prioritized 16 suggestive genome-wide significant candidate genes based on their potential involvement in skeletal metabolism. Among them, 3 candidate genes were associated with BMD in women. Notably, 2 out of these 3 genes (GPR177, p = 2.6 x 10(-13); SOX6, p = 6.4 x 10(-10)) associated with BMD in women have been successfully replicated in a large-scale meta-analysis of BMD, but none of the non-prioritized candidates (associated with BMD) did. Our results support the concept of our prioritization strategy. In the absence of direct biological support for identified genes, we highlighted the efficiency of subsequent functional characterization using publicly available expression profiling relevant to the skeletal system in cellular or whole animal models to prioritize candidate genes for further functional validation.
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| 10. |
- Hultin, Kim, et al.
(författare)
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Aerosol and bacterial emissions from Baltic Seawater
- 2011
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Ingår i: Atmospheric research. - : Elsevier BV. - 0169-8095 .- 1873-2895. ; 99:1, s. 1-14
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Tidskriftsartikel (refereegranskat)abstract
- Factors influencing the production of primary marine aerosol are of great importance to better understand the marine aerosols' impact on our climate. Bubble-bursting from whitecaps is considered the most effective mechanism for sea spray production, and a way of sea-air transfer for some bacterial species. Two coastal sites in the Baltic Sea were used to investigate aerosol and bacterial emissions from the bubble-bursting process by letting a jet of water hit a water surface within an experimental tank, mimicking the actions of breaking waves. The aerosol size distribution spectra from the two sites were similar and conservative in shape where the modes were centered at about 200 nm dry diameter. We found a distinct decrease in bubbled aerosol production with increasing water temperature. A clear diurnal cycle in bubbled aerosol production was observed, anticorrelated with both water temperature and dissolved oxygen, which to our knowledge has never been shown before. A link between decreasing aerosol production in daytime and phytoplankton activity is likely to be an important factor. Colony-forming bacteria were transferred to the atmosphere via the bubble-bursting process, with a linear relationship to their seawater concentration.
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