1. |
- Flannick, Jason, et al.
(författare)
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Data Descriptor : Sequence data and association statistics from 12,940 type 2 diabetes cases and controls
- 2017
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Ingår i: Scientific Data. - : Springer Science and Business Media LLC. - 2052-4463. ; 4
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Tidskriftsartikel (refereegranskat)abstract
- To investigate the genetic basis of type 2 diabetes (T2D) to high resolution, the GoT2D and T2D-GENES consortia catalogued variation from whole-genome sequencing of 2,657 European individuals and exome sequencing of 12,940 individuals of multiple ancestries. Over 27M SNPs, indels, and structural variants were identified, including 99% of low-frequency (minor allele frequency [MAF] 0.1-5%) non-coding variants in the whole-genome sequenced individuals and 99.7% of low-frequency coding variants in the whole-exome sequenced individuals. Each variant was tested for association with T2D in the sequenced individuals, and, to increase power, most were tested in larger numbers of individuals (> 80% of low-frequency coding variants in similar to ~82 K Europeans via the exome chip, and similar to ~90% of low-frequency non-coding variants in similar to ~44 K Europeans via genotype imputation). The variants, genotypes, and association statistics from these analyses provide the largest reference to date of human genetic information relevant to T2D, for use in activities such as T2D-focused genotype imputation, functional characterization of variants or genes, and other novel analyses to detect associations between sequence variation and T2D.
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2. |
- Fuchsberger, Christian, et al.
(författare)
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The genetic architecture of type 2 diabetes
- 2016
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 536:7614, s. 41-47
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Tidskriftsartikel (refereegranskat)abstract
- The genetic architecture of common traits, including the number, frequency, and effect sizes of inherited variants that contribute to individual risk, has been long debated. Genome-wide association studies have identified scores of common variants associated with type 2 diabetes, but in aggregate, these explain only a fraction of the heritability of this disease. Here, to test the hypothesis that lower-frequency variants explain much of the remainder, the GoT2D and T2D-GENES consortia performed whole-genome sequencing in 2,657 European individuals with and without diabetes, and exome sequencing in 12,940 individuals from five ancestry groups. To increase statistical power, we expanded the sample size via genotyping and imputation in a further 111,548 subjects. Variants associated with type 2 diabetes after sequencing were overwhelmingly common and most fell within regions previously identified by genome-wide association studies. Comprehensive enumeration of sequence variation is necessary to identify functional alleles that provide important clues to disease pathophysiology, but large-scale sequencing does not support the idea that lower-frequency variants have a major role in predisposition to type 2 diabetes.
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3. |
- Manning, Alisa, et al.
(författare)
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A Low-Frequency Inactivating AKT2 Variant Enriched in the Finnish Population Is Associated With Fasting Insulin Levels and Type 2 Diabetes Risk
- 2017
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Ingår i: Diabetes. - : AMER DIABETES ASSOC. - 0012-1797 .- 1939-327X. ; 66:7, s. 2019-2032
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Tidskriftsartikel (refereegranskat)abstract
- To identify novel coding association signals and facilitate characterization of mechanisms influencing glycemic traits and type 2 diabetes risk, we analyzed 109,215 variants derived from exome array genotyping together with an additional 390,225 variants from exome sequence in up to 39,339 normoglycemic individuals from five ancestry groups. We identified a novel association between the coding variant (p.Pro50Thr) in AKT2 and fasting plasma insulin (FI), a gene in which rare fully penetrant mutations are causal for monogenic glycemic disorders. The low-frequency allele is associated with a 12% increase in FI levels. This variant is present at 1.1% frequency in Finns but virtually absent in individuals from other ancestries. Carriers of the FI-increasing allele had increased 2-h insulin values, decreased insulin sensitivity, and increased risk of type 2 diabetes (odds ratio 1.05). In cellular studies, the AKT2-Thr50 protein exhibited a partial loss of function. We extend the allelic spectrum for coding variants in AKT2 associated with disorders of glucose homeostasis and demonstrate bidirectional effects of variants within the pleckstrin homology domain of AKT2.
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4. |
- Kesti, Jutta, et al.
(författare)
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Changes in aerosol size distributions over the Indian Ocean during different meteorological conditions
- 2020
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Ingår i: Tellus. Series B, Chemical and physical meteorology. - : Stockholm University Press. - 0280-6509 .- 1600-0889. ; 72:1
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Tidskriftsartikel (refereegranskat)abstract
- Aerosol emissions in South Asia are large. The emitted aerosols can travel significant distances and, during the Asian southwest monsoon especially, are prone to modification through cloud processing and wet scavenging while being transported. The scale of emissions and transport means that the global climate impact of these aerosols are sensitive to modification en route, but the process-level understanding is still largely lacking. In this study, we analyse long-term aerosol data measured at an observatory established in Hanimaadhoo, Republic of Maldives, to investigate the long-term properties of aerosols over the Indian Ocean as well as to understand the effect of precipitation on the aerosol particle size distribution during long-range transport. The observatory location is ideal because it is a receptor site with little local influence, and, depending on the season, receives either polluted air masses coming from the Indian subcontinent or clean marine air masses from the Indian Ocean. We analysed the sub-micron particle number size distribution measured during the years 2004-2008, and 2014-2017, and this is the first inter-seasonal long-term study of the sub-micron aerosol features in the region. The aerosol origin and its relative exposure to wet scavenging during long-range transport were analysed using back-trajectory analysis from HYSPLIT. By comparing aerosol measurements to precipitation along its transport, this study shows that there is a substantial change in particle number size distributions and concentrations depending on the amount of rainfall during transport. During the southwest monsoon season, the aerosol size distribution was notably bimodal and total particle concentrations clearly reduced in comparison with the prevailing aerosol size distribution during the northeast monsoon season. Precipitation during transport usually corresponded with a greater reduction in accumulation mode concentrations than for smaller sizes, and the shape of the median size distribution showed a clear dependence on the trajectory origin and route taken.
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5. |
- Pistone, Kristina, et al.
(författare)
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Observed correlations between aerosol and cloud properties in an Indian Ocean trade cumulus regime
- 2016
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Ingår i: Atmospheric Chemistry And Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 16:8, s. 5203-5227
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Tidskriftsartikel (refereegranskat)abstract
- There are many contributing factors which determine the micro- and macrophysical properties of clouds, including atmospheric vertical structure, dominant meteorological conditions, and aerosol concentration, all of which may be coupled to one another. In the quest to determine aerosol effects on clouds, these potential relationships must be understood. Here we describe several observed correlations between aerosol conditions and cloud and atmospheric properties in the Indian Ocean winter monsoon season. In the CARDEX (Cloud, Aerosol, Radiative forcing, Dynamics EXperiment) field campaign conducted in February and March 2012 in the northern Indian Ocean, continuous measurements were made of atmospheric precipitable water vapor (PWV) and the liquid water path (LWP) of trade cumulus clouds, concurrent with measurements of water vapor flux, cloud and aerosol vertical profiles, meteorological data, and surface and total-column aerosol from instrumentation at a ground observatory and on small unmanned aircraft. We present observations which indicate a positive correlation between aerosol and cloud LWP only when considering cases with low atmospheric water vapor (PWV < 40aEuro-kg m(-2)), a criterion which acts to filter the data to control for the natural meteorological variability in the region. We then use the aircraft and ground-based measurements to explore possible mechanisms behind this observed aerosol-LWP correlation. The increase in cloud liquid water is found to coincide with a lowering of the cloud base, which is itself attributable to increased boundary layer humidity in polluted conditions. High pollution is found to correlate with both higher temperatures and higher humidity measured throughout the boundary layer. A large-scale analysis, using satellite observations and meteorological reanalysis, corroborates these covariations: high-pollution cases are shown to originate as a highly polluted boundary layer air mass approaching the observatory from a northwesterly direction. The source air mass exhibits both higher temperatures and higher humidity in the polluted cases. While the warmer temperatures may be attributable to aerosol absorption of solar radiation over the subcontinent, the factors responsible for the coincident high humidity are less evident: the high-aerosol conditions are observed to disperse with air mass evolution, along with a weakening of the high-temperature anomaly, while the high-humidity condition is observed to strengthen in magnitude as the polluted air mass moves over the ocean toward the site of the CARDEX observations. Potential causal mechanisms of the observed correlations, including meteorological or aerosol-induced factors, are explored, though future research will be needed for a more complete and quantitative understanding of the aerosol-humidity relationship.
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6. |
- Puppala, H., et al.
(författare)
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Identification and analysis of barriers for harnessing geothermal energy in India
- 2022
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Ingår i: Renewable energy. - : Elsevier Ltd. - 0960-1481 .- 1879-0682. ; 186, s. 327-340
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Tidskriftsartikel (refereegranskat)abstract
- The Indian Government envisaged generating 10 GW using geothermal power by 2030. Reaching this milestone is linked with numerous challenges, as geothermal exploitation in India is in the nascent stages. In this work, possible barrier categories and barriers to harness geothermal energy in India are identified with the help of literature review and questionnaire-based surveys. Fuzzy Delphi method is used to find the significant barriers among the listed. Subsequently, Fuzzy Analytical Hierarchy Process (Fuzzy AHP) is used to determine the relative dominance of each barrier category and the barriers within each category. Outcomes of this research show that the resource barrier category obtained highest priority. This category includes various barriers such as (i) conceptualization of geothermal reservoir, (ii) estimation of theoretical heat energy, (iii) determination of extractable power, and (iv) selection of suitable extraction schemes. Results suggest that a comprehensive conceptual model presenting the subsurface variation of thermo-hydro-geological parameters with depth at a geothermal field can support the accurate depiction of the available and extractable thermal potential. Stability of the obtained hierarchy is examined by sensitivity analysis. Findings of this study help to identify the barriers that can be reasonably encountered and to propose developmental activities to harness geothermal energy.
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7. |
- Wilcox, Eric M., et al.
(författare)
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Black carbon solar absorption suppresses turbulence in the atmospheric boundary layer
- 2016
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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. - 0027-8424 .- 1091-6490. ; 113:42, s. 11794-11799
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Tidskriftsartikel (refereegranskat)abstract
- The introduction of cloud condensation nuclei and radiative heating by sunlight-absorbing aerosols can modify the thickness and coverage of low clouds, yielding significant radiative forcing of climate. The magnitude and sign of changes in cloud coverage and depth in response to changing aerosols are impacted by turbulent dynamics of the cloudy atmosphere, but integrated measurements of aerosol solar absorption and turbulent fluxes have not been reported thus far. Here we report such integrated measurements made from unmanned aerial vehicles (UAVs) during the CARDEX (Cloud Aerosol Radiative Forcing and Dynamics Experiment) investigation conducted over the northern Indian Ocean. The UAV and surface data reveal a reduction in turbulent kinetic energy in the surface mixed layer at the base of the atmosphere concurrent with an increase in absorbing black carbon aerosols. Polluted conditions coincide with a warmer and shallower surface mixed layer because of aerosol radiative heating and reduced turbulence. The polluted surface mixed layer was also observed to be more humid with higher relative humidity. Greater humidity enhances cloud development, as evidenced by polluted clouds that penetrate higher above the top of the surface mixed layer. Reduced entrainment of dry air into the surface layer from above the inversion capping the surface mixed layer, due to weaker turbulence, may contribute to higher relative humidity in the surface layer during polluted conditions. Measurements of turbulence are important for studies of aerosol effects on clouds. Moreover, reduced turbulence can exacerbate both the human health impacts of high concentrations of fine particles and conditions favorable for low-visibility fog events.
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