| 1. |
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| 2. |
- Arndt, D. S., et al.
(författare)
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State of the Climate in 2016
- 2017
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Ingår i: Bulletin of The American Meteorological Society - (BAMS). - 0003-0007 .- 1520-0477. ; 98:8, s. S1-S280
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Tidskriftsartikel (refereegranskat)abstract
- In 2016, the dominant greenhouse gases released into Earth's atmosphere-carbon dioxide, methane, and nitrous oxide-continued to increase and reach new record highs. The 3.5 +/- 0.1 ppm rise in global annual mean carbon dioxide from 2015 to 2016 was the largest annual increase observed in the 58-year measurement record. The annual global average carbon dioxide concentration at Earth's surface surpassed 400 ppm (402.9 +/- 0.1 ppm) for the first time in the modern atmospheric measurement record and in ice core records dating back as far as 800000 years. One of the strongest El Nino events since at least 1950 dissipated in spring, and a weak La Nina evolved later in the year. Owing at least in part to the combination of El Nino conditions early in the year and a long-term upward trend, Earth's surface observed record warmth for a third consecutive year, albeit by a much slimmer margin than by which that record was set in 2015. Above Earth's surface, the annual lower troposphere temperature was record high according to all datasets analyzed, while the lower stratospheric temperature was record low according to most of the in situ and satellite datasets. Several countries, including Mexico and India, reported record high annual temperatures while many others observed near-record highs. A week-long heat wave at the end of April over the northern and eastern Indian peninsula, with temperatures surpassing 44 degrees C, contributed to a water crisis for 330 million people and to 300 fatalities. In the Arctic the 2016 land surface temperature was 2.0 degrees C above the 1981-2010 average, breaking the previous record of 2007, 2011, and 2015 by 0.8 degrees C, representing a 3.5 degrees C increase since the record began in 1900. The increasing temperatures have led to decreasing Arctic sea ice extent and thickness. On 24 March, the sea ice extent at the end of the growth season saw its lowest maximum in the 37-year satellite record, tying with 2015 at 7.2% below the 1981-2010 average. The September 2016 Arctic sea ice minimum extent tied with 2007 for the second lowest value on record, 33% lower than the 1981-2010 average. Arctic sea ice cover remains relatively young and thin, making it vulnerable to continued extensive melt. The mass of the Greenland Ice Sheet, which has the capacity to contribute similar to 7 m to sea level rise, reached a record low value. The onset of its surface melt was the second earliest, after 2012, in the 37-year satellite record. Sea surface temperature was record high at the global scale, surpassing the previous record of 2015 by about 0.01 degrees C. The global sea surface temperature trend for the 21st century-to-date of +0.162 degrees C decade(-1) is much higher than the longer term 1950-2016 trend of +0.100 degrees C decade(-1). Global annual mean sea level also reached a new record high, marking the sixth consecutive year of increase. Global annual ocean heat content saw a slight drop compared to the record high in 2015. Alpine glacier retreat continued around the globe, and preliminary data indicate that 2016 is the 37th consecutive year of negative annual mass balance. Across the Northern Hemisphere, snow cover for each month from February to June was among its four least extensive in the 47-year satellite record. Continuing a pattern below the surface, record high temperatures at 20-m depth were measured at all permafrost observatories on the North Slope of Alaska and at the Canadian observatory on northernmost Ellesmere Island. In the Antarctic, record low monthly surface pressures were broken at many stations, with the southern annular mode setting record high index values in March and June. Monthly high surface pressure records for August and November were set at several stations. During this period, record low daily and monthly sea ice extents were observed, with the November mean sea ice extent more than 5 standard deviations below the 1981-2010 average. These record low sea ice values contrast sharply with the record high values observed during 2012-14. Over the region, springtime Antarctic stratospheric ozone depletion was less severe relative to the 1991-2006 average, but ozone levels were still low compared to pre-1990 levels. Closer to the equator, 93 named tropical storms were observed during 2016, above the 1981-2010 average of 82, but fewer than the 101 storms recorded in 2015. Three basins-the North Atlantic, and eastern and western North Pacific-experienced above-normal activity in 2016. The Australian basin recorded its least active season since the beginning of the satellite era in 1970. Overall, four tropical cyclones reached the Saffir-Simpson category 5 intensity level. The strong El Nino at the beginning of the year that transitioned to a weak La Nina contributed to enhanced precipitation variability around the world. Wet conditions were observed throughout the year across southern South America, causing repeated heavy flooding in Argentina, Paraguay, and Uruguay. Wetter-than-usual conditions were also observed for eastern Europe and central Asia, alleviating the drought conditions of 2014 and 2015 in southern Russia. In the United States, California had its first wetter-than-average year since 2012, after being plagued by drought for several years. Even so, the area covered by drought in 2016 at the global scale was among the largest in the post-1950 record. For each month, at least 12% of land surfaces experienced severe drought conditions or worse, the longest such stretch in the record. In northeastern Brazil, drought conditions were observed for the fifth consecutive year, making this the longest drought on record in the region. Dry conditions were also observed in western Bolivia and Peru; it was Bolivia's worst drought in the past 25 years. In May, with abnormally warm and dry conditions already prevailing over western Canada for about a year, the human-induced Fort McMurray wildfire burned nearly 590000 hectares and became the costliest disaster in Canadian history, with $3 billion (U.S. dollars) in insured losses.
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| 3. |
- Stanaway, Jeffrey D., et al.
(författare)
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Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks for 195 countries and territories, 1990-2017: A systematic analysis for the Global Burden of Disease Study 2017
- 2018
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Ingår i: The Lancet. - 1474-547X .- 0140-6736. ; 392:10159, s. 1923-1994
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Tidskriftsartikel (refereegranskat)abstract
- Background The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 comparative risk assessment (CRA) is a comprehensive approach to risk factor quantification that offers a useful tool for synthesising evidence on risks and risk-outcome associations. With each annual GBD study, we update the GBD CRA to incorporate improved methods, new risks and risk-outcome pairs, and new data on risk exposure levels and risk- outcome associations. Methods We used the CRA framework developed for previous iterations of GBD to estimate levels and trends in exposure, attributable deaths, and attributable disability-adjusted life-years (DALYs), by age group, sex, year, and location for 84 behavioural, environmental and occupational, and metabolic risks or groups of risks from 1990 to 2017. This study included 476 risk-outcome pairs that met the GBD study criteria for convincing or probable evidence of causation. We extracted relative risk and exposure estimates from 46 749 randomised controlled trials, cohort studies, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. Using the counterfactual scenario of theoretical minimum risk exposure level (TMREL), we estimated the portion of deaths and DALYs that could be attributed to a given risk. We explored the relationship between development and risk exposure by modelling the relationship between the Socio-demographic Index (SDI) and risk-weighted exposure prevalence and estimated expected levels of exposure and risk-attributable burden by SDI. Finally, we explored temporal changes in risk-attributable DALYs by decomposing those changes into six main component drivers of change as follows: (1) population growth; (2) changes in population age structures; (3) changes in exposure to environmental and occupational risks; (4) changes in exposure to behavioural risks; (5) changes in exposure to metabolic risks; and (6) changes due to all other factors, approximated as the risk-deleted death and DALY rates, where the risk-deleted rate is the rate that would be observed had we reduced the exposure levels to the TMREL for all risk factors included in GBD 2017.
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| 4. |
- Tuson, A., et al.
(författare)
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TESS and CHEOPS discover two warm sub-Neptunes transiting the bright K-dwarf HD 15906
- 2023
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Ingår i: Monthly Notices of the Royal Astronomical Society. - 0035-8711 .- 1365-2966. ; 523:2, s. 3090-3118
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Tidskriftsartikel (refereegranskat)abstract
- We report the discovery of two warm sub-Neptunes transiting the bright (G = 9.5 mag) K-dwarf HD 15906 (TOI 461, TIC 4646810). This star was observed by the Transiting Exoplanet Survey Satellite (TESS) in sectors 4 and 31, revealing two small transiting planets. The inner planet, HD 15906 b, was detected with an unambiguous period but the outer planet, HD 15906 c, showed only two transits separated by ∼ 734 d, leading to 36 possible values of its period. We performed follow-up observations with the CHaracterising ExOPlanet Satellite (CHEOPS) to confirm the true period of HD 15906 c and improve the radius precision of the two planets. From TESS, CHEOPS, and additional ground-based photometry, we find that HD 15906 b has a radius of 2.24 ± 0.08 R and a period of 10.924709 ± 0.000032 d, whilst HD 15906 c has a radius of 2.93+−000607 R and a period of 21.583298+−00000055000052 d. Assuming zero bond albedo and full day-night heat redistribution, the inner and outer planet have equilibrium temperatures of 668 ± 13 K and 532 ± 10 K, respectively. The HD 15906 system has become one of only six multiplanet systems with two warm (700 K) sub-Neptune sized planets transiting a bright star (G ≤ 10 mag). It is an excellent target for detailed characterization studies to constrain the composition of sub-Neptune planets and test theories of planet formation and evolution.
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| 5. |
- Aaron-Morrison, Arlene P., et al.
(författare)
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State of the climate in 2014
- 2015
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Ingår i: Bulletin of the American Meteorological Society. - : American Meteorological Society. - 0003-0007 .- 1520-0477. ; 96
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Tidskriftsartikel (refereegranskat)abstract
- Most of the dozens of essential climate variables monitored each year in this report continued to follow their long-term trends in 2014, with several setting new records. Carbon dioxide, methane, and nitrous oxide-the major greenhouse gases released into Earth's atmosphere-once again all reached record high average atmospheric concentrations for the year. Carbon dioxide increased by 1.9 ppm to reach a globally averaged value of 397.2 ppm for 2014. Altogether, 5 major and 15 minor greenhouse gases contributed 2.94 W m-2 of direct radiative forcing, which is 36% greater than their contributions just a quarter century ago. Accompanying the record-high greenhouse gas concentrations was nominally the highest annual global surface temperature in at least 135 years of modern record keeping, according to four independent observational analyses. The warmth was distributed widely around the globe's land areas, Europe observed its warmest year on record by a large margin, with close to two dozen countries breaking their previous national temperature records; many countries in Asia had annual temperatures among their 10 warmest on record; Africa reported above-average temperatures across most of the continent throughout 2014; Australia saw its third warmest year on record, following record heat there in 2013; Mexico had its warmest year on record; and Argentina and Uruguay each had their second warmest year on record. Eastern North America was the only major region to observe a below-average annual temperature. But it was the oceans that drove the record global surface temperature in 2014. Although 2014 was largely ENSO-neutral, the globally averaged sea surface temperature (SST) was the highest on record. The warmth was particularly notable in the North Pacific Ocean where SST anomalies signaled a transition from a negative to positive phase of the Pacific decadal oscillation. In the winter of 2013/14, unusually warm water in the northeast Pacific was associated with elevated ocean heat content anomalies and elevated sea level in the region. Globally, upper ocean heat content was record high for the year, reflecting the continued increase of thermal energy in the oceans, which absorb over 90% of Earth's excess heat from greenhouse gas forcing. Owing to both ocean warming and land ice melt contributions, global mean sea level in 2014 was also record high and 67 mm greater than the 1993 annual mean, when satellite altimetry measurements began. Sea surface salinity trends over the past decade indicate that salty regions grew saltier while fresh regions became fresher, suggestive of an increased hydrological cycle over the ocean expected with global warming. As in previous years, these patterns are reflected in 2014 subsurface salinity anomalies as well. With a now decade-long trans-basin instrument array along 26°N, the Atlantic meridional overturning circulation shows a decrease in transport of-4.2 ± 2.5 Sv decade-1. Precipitation was quite variable across the globe. On balance, precipitation over the world's oceans was above average, while below average across land surfaces. Drought continued in southeastern Brazil and the western United States. Heavy rain during April-June led to devastating floods in Canada's Eastern Prairies. Above-normal summer monsoon rainfall was observed over the southern coast of West Africa, while drier conditions prevailed over the eastern Sahel. Generally, summer monsoon rainfall over eastern Africa was above normal, except in parts of western South Sudan and Ethiopia. The south Asian summer monsoon in India was below normal, with June record dry. Across the major tropical cyclone basins, 91 named storms were observed during 2014, above the 1981-2010 global average of 82. The Eastern/Central Pacific and South Indian Ocean basins experienced significantly above-normal activity in 2014; all other basins were either at or below normal. The 22 named storms in the Eastern/Central Pacific was the basin's most since 1992. Similar to 2013, the North Atlantic season was quieter than most years of the last two decades with respect to the number of storms, despite the absence of El Niño conditions during both years. In higher latitudes and at higher elevations, increased warming continued to be visible in the decline of glacier mass balance, increasing permafrost temperatures, and a deeper thawing layer in seasonally frozen soil. In the Arctic, the 2014 temperature over land areas was the fourth highest in the 115-year period of record and snow melt occurred 20-30 days earlier than the 1998-2010 average. The Greenland Ice Sheet experienced extensive melting in summer 2014. The extent of melting was above the 1981-2010 average for 90% of the melt season, contributing to the second lowest average summer albedo over Greenland since observations began in 2000 and a record-low albedo across the ice sheet for August. On the North Slope of Alaska, new record high temperatures at 20-m depth were measured at four of five permafrost observatories. In September, Arctic minimum sea ice extent was the sixth lowest since satellite records began in 1979. The eight lowest sea ice extents during this period have occurred in the last eight years. Conversely, in the Antarctic, sea ice extent countered its declining trend and set several new records in 2014, including record high monthly mean sea ice extent each month from April to November. On 20 September, a record large daily Antarctic sea ice extent of 20.14 × 106 km2 occurred. The 2014 Antarctic stratospheric ozone hole was 20.9 million km2 when averaged from 7 September to 13 October, the sixth smallest on record and continuing a decrease, albeit statistically insignificant, in area since 1998.
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| 6. |
- Birney, Ewan, et al.
(författare)
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Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project
- 2007
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 447:7146, s. 799-816
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Tidskriftsartikel (refereegranskat)abstract
- We report the generation and analysis of functional data from multiple, diverse experiments performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project. These data have been further integrated and augmented by a number of evolutionary and computational analyses. Together, our results advance the collective knowledge about human genome function in several major areas. First, our studies provide convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts, including non-protein-coding transcripts, and those that extensively overlap one another. Second, systematic examination of transcriptional regulation has yielded new understanding about transcription start sites, including their relationship to specific regulatory sequences and features of chromatin accessibility and histone modification. Third, a more sophisticated view of chromatin structure has emerged, including its inter-relationship with DNA replication and transcriptional regulation. Finally, integration of these new sources of information, in particular with respect to mammalian evolution based on inter- and intra-species sequence comparisons, has yielded new mechanistic and evolutionary insights concerning the functional landscape of the human genome. Together, these studies are defining a path for pursuit of a more comprehensive characterization of human genome function.
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| 7. |
- Botvinik-Nezer, Rotem, et al.
(författare)
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Variability in the analysis of a single neuroimaging dataset by many teams
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 582, s. 84-88
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Tidskriftsartikel (refereegranskat)abstract
- Data analysis workflows in many scientific domains have become increasingly complex and flexible. Here we assess the effect of this flexibility on the results of functional magnetic resonance imaging by asking 70 independent teams to analyse the same dataset, testing the same 9 ex-ante hypotheses(1). The flexibility of analytical approaches is exemplified by the fact that no two teams chose identical workflows to analyse the data. This flexibility resulted in sizeable variation in the results of hypothesis tests, even for teams whose statistical maps were highly correlated at intermediate stages of the analysis pipeline. Variation in reported results was related to several aspects of analysis methodology. Notably, a meta-analytical approach that aggregated information across teams yielded a significant consensus in activated regions. Furthermore, prediction markets of researchers in the field revealed an overestimation of the likelihood of significant findings, even by researchers with direct knowledge of the dataset(2-5). Our findings show that analytical flexibility can have substantial effects on scientific conclusions, and identify factors that may be related to variability in the analysis of functional magnetic resonance imaging. The results emphasize the importance of validating and sharing complex analysis workflows, and demonstrate the need for performing and reporting multiple analyses of the same data. Potential approaches that could be used to mitigate issues related to analytical variability are discussed. The results obtained by seventy different teams analysing the same functional magnetic resonance imaging dataset show substantial variation, highlighting the influence of analytical choices and the importance of sharing workflows publicly and performing multiple analyses.
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| 8. |
- Ferrari, Raffaele, et al.
(författare)
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Frontotemporal dementia and its subtypes: a genome-wide association study.
- 2014
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Ingår i: Lancet Neurology. - 1474-4465. ; 13:7, s. 686-699
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Tidskriftsartikel (refereegranskat)abstract
- Frontotemporal dementia (FTD) is a complex disorder characterised by a broad range of clinical manifestations, differential pathological signatures, and genetic variability. Mutations in three genes-MAPT, GRN, and C9orf72-have been associated with FTD. We sought to identify novel genetic risk loci associated with the disorder.
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| 9. |
- Hou, Liping, et al.
(författare)
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Genome-wide association study of 40,000 individuals identifies two novel loci associated with bipolar disorder.
- 2016
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Ingår i: Human molecular genetics. - : Oxford University Press (OUP). - 1460-2083 .- 0964-6906. ; 25:15, s. 3383-94
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Tidskriftsartikel (refereegranskat)abstract
- Bipolar disorder (BD) is a genetically complex mental illness characterized by severe oscillations of mood and behavior. Genome-wide association studies (GWAS) have identified several risk loci that together account for a small portion of the heritability. To identify additional risk loci, we performed a two-stage meta-analysis of >9 million genetic variants in 9,784 bipolar disorder patients and 30,471 controls, the largest GWAS of BD to date. In this study, to increase power we used ∼2,000 lithium-treated cases with a long-term diagnosis of BD from the Consortium on Lithium Genetics, excess controls, and analytic methods optimized for markers on the X-chromosome. In addition to four known loci, results revealed genome-wide significant associations at two novel loci: an intergenic region on 9p21.3 (rs12553324, p=5.87×10(-9); odds ratio=1.12) and markers within ERBB2 (rs2517959, p=4.53×10(-9); odds ratio=1.13). No significant X-chromosome associations were detected and X-linked markers explained very little BD heritability. The results add to a growing list of common autosomal variants involved in BD and illustrate the power of comparing well-characterized cases to an excess of controls in GWAS.
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| 10. |
- Conti, David, V, et al.
(författare)
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Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction
- 2021
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Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 53:1, s. 65-75
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Tidskriftsartikel (refereegranskat)abstract
- Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.06 (95% confidence interval (CI), 4.84-5.29) for men of European ancestry to 3.74 (95% CI, 3.36-4.17) for men of African ancestry. Men of African ancestry were estimated to have a mean GRS that was 2.18-times higher (95% CI, 2.14-2.22), and men of East Asian ancestry 0.73-times lower (95% CI, 0.71-0.76), than men of European ancestry. These findings support the role of germline variation contributing to population differences in prostate cancer risk, with the GRS offering an approach for personalized risk prediction. A meta-analysis of genome-wide association studies across different populations highlights new risk loci and provides a genetic risk score that can stratify prostate cancer risk across ancestries.
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| 11. |
- Dieterich, Lothar C., et al.
(författare)
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Transcriptional profiling of human glioblastoma vessels indicates a key role of VEGF-A and TGFβ2 in vascular abnormalization
- 2012
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Ingår i: Journal of Pathology. - : Wiley. - 0022-3417 .- 1096-9896. ; 228:3, s. 378-390
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Tidskriftsartikel (refereegranskat)abstract
- Glioblastoma are aggressive astrocytic brain tumours characterized by microvascular proliferation and an abnormal vasculature, giving rise to brain oedema and increased patient morbidity. Here, we have characterized the transcriptome of tumour-associated blood vessels and describe a gene signature clearly associated with pleomorphic, pathologically altered vessels in human glioblastoma (grade IV glioma). We identified 95 genes differentially expressed in glioblastoma vessels, while no significant differences in gene expression were detected between vessels in non-malignant brain and grade II glioma. Differential vascular expression of ANGPT2, CD93, ESM1, ELTD1, FILIP1L and TENC1 in human glioblastoma was validated by immunohistochemistry, using a tissue microarray. Through qPCR analysis of gene induction in primary endothelial cells, we provide evidence that increased VEGF-A and TGFβ2 signalling in the tumour microenvironment is sufficient to invoke many of the changes in gene expression noted in glioblastoma vessels. Notably, we found an enrichment of Smad target genes within the distinct gene signature of glioblastoma vessels and a significant increase of Smad signalling complexes in the vasculature of human glioblastoma in situ. This indicates a key role of TGFβ signalling in regulating vascular phenotype and suggests that, in addition to VEGF-A, TGFβ2 may represent a new target for vascular normalization therapy.
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| 12. |
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| 13. |
- Huerta, E. A., et al.
(författare)
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Enabling real-time multi-messenger astrophysics discoveries with deep learning
- 2019
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Ingår i: Nature reviews physics. - : Springer Science and Business Media LLC. - 2522-5820. ; 1:10, s. 600-608
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Forskningsöversikt (refereegranskat)abstract
- Multi-messenger astrophysics is a fast-growing, interdisciplinary field that combines data, which vary in volume and speed of data processing, from many different instruments that probe the Universe using different cosmic messengers: electromagnetic waves, cosmic rays, gravitational waves and neutrinos. In this Expert Recommendation, we review the key challenges of real-time observations of gravitational wave sources and their electromagnetic and astroparticle counterparts, and make a number of recommendations to maximize their potential for scientific discovery. These recommendations refer to the design of scalable and computationally efficient machine learning algorithms; the cyber-infrastructure to numerically simulate astrophysical sources, and to process and interpret multi-messenger astrophysics data; the management of gravitational wave detections to trigger real-time alerts for electromagnetic and astroparticle follow-ups; a vision to harness future developments of machine learning and cyber-infrastructure resources to cope with the big-data requirements; and the need to build a community of experts to realize the goals of multi-messenger astrophysics. A group of experts suggests ways in which deep learning can be used to enhance the potential for discovery in multi-messenger astrophysics.
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| 14. |
- Jiang, Mingkai, et al.
(författare)
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The fate of carbon in a mature forest under carbon dioxide enrichment
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 580:7802, s. 227-231
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Tidskriftsartikel (refereegranskat)abstract
- Atmospheric carbon dioxide enrichment (eCO2) can enhance plant carbon uptake and growth1–5, thereby providing an important negative feedback to climate change by slowing the rate of increase of the atmospheric CO2 concentration6. Although evidence gathered from young aggrading forests has generally indicated a strong CO2 fertilization effect on biomass growth3–5, it is unclear whether mature forests respond to eCO2 in a similar way. In mature trees and forest stands7–10, photosynthetic uptake has been found to increase under eCO2 without any apparent accompanying growth response, leaving the fate of additional carbon fixed under eCO2 unclear4,5,7–11. Here using data from the first ecosystem-scale Free-Air CO2 Enrichment (FACE) experiment in a mature forest, we constructed a comprehensive ecosystem carbon budget to track the fate of carbon as the forest responded to four years of eCO2 exposure. We show that, although the eCO2 treatment of +150 parts per million (+38 per cent) above ambient levels induced a 12 per cent (+247 grams of carbon per square metre per year) increase in carbon uptake through gross primary production, this additional carbon uptake did not lead to increased carbon sequestration at the ecosystem level. Instead, the majority of the extra carbon was emitted back into the atmosphere via several respiratory fluxes, with increased soil respiration alone accounting for half of the total uptake surplus. Our results call into question the predominant thinking that the capacity of forests to act as carbon sinks will be generally enhanced under eCO2, and challenge the efficacy of climate mitigation strategies that rely on ubiquitous CO2 fertilization as a driver of increased carbon sinks in global forests.
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| 15. |
- Majounie, Elisa, et al.
(författare)
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Frequency of the C9orf72 hexanucleotide repeat expansion in patients with amyotrophic lateral sclerosis and frontotemporal dementia: a cross-sectional study
- 2012
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Ingår i: Lancet Neurology. - 1474-4465. ; 11:4, s. 323-330
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Tidskriftsartikel (refereegranskat)abstract
- Background We aimed to accurately estimate the frequency of a hexanucleotide repeat expansion in C9orf72 that has been associated with a large proportion of cases of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Methods We screened 4448 patients diagnosed with ALS (El Escorial criteria) and 1425 patients with FTD (Lund-Manchester criteria) from 17 regions worldwide for the GGGGCC hexanucleotide expansion using a repeat-primed PCR assay. We assessed familial disease status on the basis of self-reported family history of similar neurodegenerative diseases at the time of sample collection. We compared haplotype data for 262 patients carrying the expansion with the known Finnish founder risk haplotype across the chromosomal locus. We calculated age-related penetrance using the Kaplan-Meier method with data for 603 individuals with the expansion. Findings In patients with sporadic ALS, we identified the repeat expansion in 236 (7.0%) of 3377 white individuals from the USA, Europe, and Australia, two (4.1%) of 49 black individuals from the USA, and six (8.3%) of 72 Hispanic individuals from the USA. The mutation was present in 217 (39.3%) of 552 white individuals with familial MS from Europe and the USA. 59 (6.0%) of 981 white Europeans with sporadic FTD had the mutation, as did 99 (24.8%) of 400 white Europeans with familial FTD. Data for other ethnic groups were sparse, but we identified one Asian patient with familial ALS (from 20 assessed) and two with familial FTD (from three assessed) who carried the mutation. The mutation was not carried by the three Native Americans or 360 patients from Asia or the Pacific Islands with sporadic MS who were tested, or by 41 Asian patients with sporadic FTD. All patients with the repeat expansion had (partly or fully) the founder haplotype, suggesting a one-off expansion occurring about 1500 years ago. The pathogenic expansion was non-penetrant in individuals younger than 35 years, 50% penetrant by 58 years, and almost fully penetrant by 80 years. Interpretation A common Mendelian genetic lesion in C9472 is implicated in many cases of sporadic and familial ALS and FTD. Testing for this pathogenic expansion should be considered in the management and genetic counselling of patients with these fatal neurodegenerative diseases.
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| 16. |
- Manzoni, Claudia, et al.
(författare)
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Genome-wide analyses reveal a potential role for the MAPT, MOBP, and APOE loci in sporadic frontotemporal dementia
- 2024
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Ingår i: American Journal of Human Genetics. - 0002-9297. ; 111:7, s. 1316-1329
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Tidskriftsartikel (refereegranskat)abstract
- Frontotemporal dementia (FTD) is the second most common cause of early-onset dementia after Alzheimer disease (AD). Efforts in the field mainly focus on familial forms of disease (fFTDs), while studies of the genetic etiology of sporadic FTD (sFTD) have been less common. In the current work, we analyzed 4,685 sFTD cases and 15,308 controls looking for common genetic determinants for sFTD. We found a cluster of variants at the MAPT (rs199443; p = 2.5 × 10−12, OR = 1.27) and APOE (rs6857; p = 1.31 × 10−12, OR = 1.27) loci and a candidate locus on chromosome 3 (rs1009966; p = 2.41 × 10−8, OR = 1.16) in the intergenic region between RPSA and MOBP, contributing to increased risk for sFTD through effects on expression and/or splicing in brain cortex of functionally relevant in-cis genes at the MAPT and RPSA-MOBP loci. The association with the MAPT (H1c clade) and RPSA-MOBP loci may suggest common genetic pleiotropy across FTD and progressive supranuclear palsy (PSP) (MAPT and RPSA-MOBP loci) and across FTD, AD, Parkinson disease (PD), and cortico-basal degeneration (CBD) (MAPT locus). Our data also suggest population specificity of the risk signals, with MAPT and APOE loci associations mainly driven by Central/Nordic and Mediterranean Europeans, respectively. This study lays the foundations for future work aimed at further characterizing population-specific features of potential FTD-discriminant APOE haplotype(s) and the functional involvement and contribution of the MAPT H1c haplotype and RPSA-MOBP loci to pathogenesis of sporadic forms of FTD in brain cortex.
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| 17. |
- Monzani, Dario, et al.
(författare)
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Patient Preferences for Lung Cancer Treatments: A Study Protocol for a Preference Survey Using Discrete Choice Experiment and Swing Weighting
- 2021
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Ingår i: Frontiers in Medicine. - : Frontiers Media SA. - 2296-858X. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Background: Advanced treatment options for non-small cell lung cancer (NSCLC) consist of immunotherapy, chemotherapy, or a combination of both. Decisions surrounding NSCLC can be considered as preference-sensitive because multiple treatments exist that vary in terms of mode of administration, treatment schedules, and benefit–risk profiles. As part of the IMI PREFER project, we developed a protocol for an online preference survey for NSCLC patients exploring differences in preferences according to patient characteristics (preference heterogeneity). Moreover, this study will evaluate and compare the use of two different preference elicitation methods, the discrete choice experiment (DCE) and the swing weighting (SW) task. Finally, the study explores how demographic (i.e., age, gender, and educational level) and clinical (i.e., cancer stage and line of treatment) information, health literacy, health locus of control, and quality of life may influence or explain patient preferences and the usefulness of a digital interactive tool in providing information on preference elicitation tasks according to patients.Methods: An online survey will be implemented with the aim to recruit 510 NSCLC patients in Belgium and Italy. Participants will be randomized 50:50 to first receive either the DCE or the SW. The survey will also collect information on participants' disease-related status, health locus of control, health literacy, quality of life, and perception of the educational tool.Discussion: This protocol outlines methodological and practical steps to quantitatively elicit and study patient preferences for NSCLC treatment alternatives. Results from this study will increase the understanding of which treatment aspects are most valued by NSCLC patients to inform decision-making in drug development, regulatory approval, and reimbursement. Methodologically, the comparison between the DCE and the SW task will be valuable to gain information on how these preference methods perform against each other in eliciting patient preferences. Overall, this protocol may assist researchers, drug developers, and decision-makers in designing quantitative patient preferences into decision-making along the medical product life cycle.
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| 18. |
- Patterson, Nick, et al.
(författare)
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Large-scale migration into Britain during the Middle to Late Bronze Age
- 2022
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Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; , s. 588-594
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Tidskriftsartikel (refereegranskat)abstract
- Present-day people from England and Wales harbour more ancestry derived from Early European Farmers (EEF) than people of the Early Bronze Age1. To understand this, we generated genome-wide data from 793 individuals, increasing data from the Middle to Late Bronze and Iron Age in Britain by 12-fold, and Western and Central Europe by 3.5-fold. Between 1000 and 875 BC, EEF ancestry increased in southern Britain (England and Wales) but not northern Britain (Scotland) due to incorporation of migrants who arrived at this time and over previous centuries, and who were genetically most similar to ancient individuals from France. These migrants contributed about half the ancestry of Iron Age people of England and Wales, thereby creating a plausible vector for the spread of early Celtic languages into Britain. These patterns are part of a broader trend of EEF ancestry becoming more similar across central and western Europe in the Middle to Late Bronze Age, coincident with archaeological evidence of intensified cultural exchange2-6. There was comparatively less gene flow from continental Europe during the Iron Age, and Britain's independent genetic trajectory is also reflected in the rise of the allele conferring lactase persistence to ~50% by this time compared to ~7% in central Europe where it rose rapidly in frequency only a millennium later. This suggests that dairy products were used in qualitatively different ways in Britain and in central Europe over this period.
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| 19. |
- Sánchez-Cano, Beatriz, et al.
(författare)
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Solar Energetic Particle Events Detected in the Housekeeping Data of the European Space Agency's Spacecraft Flotilla in the Solar System
- 2023
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Ingår i: Space Weather. - : American Geophysical Union (AGU). - 1542-7390. ; 21:8
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Tidskriftsartikel (refereegranskat)abstract
- Despite the growing importance of planetary Space Weather forecasting and radiation protection for science and robotic exploration and the need for accurate Space Weather monitoring and predictions, only a limited number of spacecraft have dedicated instrumentation for this purpose. However, every spacecraft (planetary or astronomical) has hundreds of housekeeping sensors distributed across the spacecraft, some of which can be useful to detect radiation hazards produced by solar particle events. In particular, energetic particles that impact detectors and subsystems on a spacecraft can be identified by certain housekeeping sensors, such as the Error Detection and Correction (EDAC) memory counters, and their effects can be assessed. These counters typically have a sudden large increase in a short time in their error counts that generally match the arrival of energetic particles to the spacecraft. We investigate these engineering datasets for scientific purposes and perform a feasibility study of solar energetic particle event detections using EDAC counters from seven European Space Agency Solar System missions: Venus Express, Mars Express, ExoMars-Trace Gas Orbiter, Rosetta, BepiColombo, Solar Orbiter, and Gaia. Six cases studies, in which the same event was observed by different missions at different locations in the inner Solar System are analyzed. The results of this study show how engineering sensors, for example, EDAC counters, can be used to infer information about the solar particle environment at each spacecraft location. Therefore, we demonstrate the potential of the various EDAC to provide a network of solar particle detections at locations where no scientific observations of this kind are available.
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| 20. |
- Wang, Anqi, et al.
(författare)
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Characterizing prostate cancer risk through multi-ancestry genome-wide discovery of 187 novel risk variants
- 2023
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Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 55:12, s. 2065-2074
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Tidskriftsartikel (refereegranskat)abstract
- The transferability and clinical value of genetic risk scores (GRSs) across populations remain limited due to an imbalance in genetic studies across ancestrally diverse populations. Here we conducted a multi-ancestry genome-wide association study of 156,319 prostate cancer cases and 788,443 controls of European, African, Asian and Hispanic men, reflecting a 57% increase in the number of non-European cases over previous prostate cancer genome-wide association studies. We identified 187 novel risk variants for prostate cancer, increasing the total number of risk variants to 451. An externally replicated multi-ancestry GRS was associated with risk that ranged from 1.8 (per standard deviation) in African ancestry men to 2.2 in European ancestry men. The GRS was associated with a greater risk of aggressive versus non-aggressive disease in men of African ancestry (P = 0.03). Our study presents novel prostate cancer susceptibility loci and a GRS with effective risk stratification across ancestry groups.
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| 21. |
- Barrenäs, Fredrik, et al.
(författare)
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Interleukin-15 response signature predicts RhCMV/SIV vaccine efficacy
- 2021
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Ingår i: PLoS Pathogens. - : Public Library of Science (PLoS). - 1553-7366 .- 1553-7374. ; 17:7
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Tidskriftsartikel (refereegranskat)abstract
- Simian immunodeficiency virus (SIV) challenge of rhesus macaques (RMs) vaccinated with strain 68-1 Rhesus Cytomegalovirus (RhCMV) vectors expressing SIV proteins (RhCMV/SIV) results in a binary outcome: stringent control and subsequent clearance of highly pathogenic SIV in similar to 55% of vaccinated RMs with no protection in the remaining 45%. Although previous work indicates that unconventionally restricted, SIV-specific, effector-memory (EM)-biased CD8(+) T cell responses are necessary for efficacy, the magnitude of these responses does not predict efficacy, and the basis of protection vs. non-protection in 68-1 RhCMV/SIV vector-vaccinated RMs has not been elucidated. Here, we report that 68-1 RhCMV/SIV vector administration strikingly alters the whole blood transcriptome of vaccinated RMs, with the sustained induction of specific immune-related pathways, including immune cell, toll-like receptor (TLR), inflammasome/cell death, and interleukin-15 (IL-15) signaling, significantly correlating with subsequent vaccine efficacy. Treatment of a separate RM cohort with IL-15 confirmed the central involvement of this cytokine in the protection signature, linking the major innate and adaptive immune gene expression networks that correlate with RhCMV/SIV vaccine efficacy. This change-from-baseline IL-15 response signature was also demonstrated to significantly correlate with vaccine efficacy in an independent validation cohort of vaccinated and challenged RMs. The differential IL-15 gene set response to vaccination strongly correlated with the pre-vaccination activity of this pathway, with reduced baseline expression of IL-15 response genes significantly correlating with higher vaccine-induced induction of IL-15 signaling and subsequent vaccine protection, suggesting that a robust de novo vaccine-induced IL-15 signaling response is needed to program vaccine efficacy. Thus, the RhCMV/SIV vaccine imparts a coordinated and persistent induction of innate and adaptive immune pathways featuring IL-15, a known regulator of CD8(+) T cell function, that support the ability of vaccine-elicited unconventionally restricted CD8(+) T cells to mediate protection against SIV challenge.
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| 22. |
- Bekers, Elise M., et al.
(författare)
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Soft tissue angiofibroma : Clinicopathologic, immunohistochemical and molecular analysis of 14 cases
- 2017
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Ingår i: Genes Chromosomes and Cancer. - : Wiley. - 1045-2257. ; 56:10, s. 750-757
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Tidskriftsartikel (refereegranskat)abstract
- Soft tissue angiofibroma is rare and has characteristic histomorphological and genetic features. For diagnostic purposes, there are no specific antibodies available. Fourteen lesions (6 females, 8 males; age range 7-67 years) of the lower extremities (12) and trunk (2) were investigated by immunohistochemistry, including for the first time NCOA2. NCOA2 was also tested in a control group of other spindle cell lesions. The known fusion-genes (AHRR-NCOA2 and GTF2I-NCOA2) were examined using RT-PCR in order to evaluate their diagnostic value. Cases in which no fusion gene was detected were additionally analysed by RNA sequencing. All cases tested showed nuclear expression of NCOA2. However, this was not specific since other spindle cell neoplasms also expressed this marker in a high percentage of cases. Other variably positive markers were EMA, SMA, desmin and CD34. STAT6 was negative in the cases tested. By RT-PCR for the most frequently observed fusions, an AHRR-NCOA2 fusion transcript was found in 9/14 cases. GTF2I-NCOA2 was not detected in the remaining cases (n = 3). RNA sequencing revealed three additional positive cases; two harbored a AHRR-NCOA2 fusion and one case a novel GAB1-ABL1 fusion. Two cases failed molecular analysis due to poor RNA quality. In conclusion, the AHRR-NCOA2 fusion is a frequent finding in soft tissue angiofibroma, while GTF2I-NCOA2 seems to be a rare genetic event. For the first time, we report a GAB1-ABL1 fusion in a soft tissue angiofibroma of a child. Nuclear expression of NCOA2 is not discriminating when compared with other spindle cell neoplasms.
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| 23. |
- de Mello, Vanessa D., et al.
(författare)
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Indolepropionic acid and novel lipid metabolites are associated with a lower risk of type 2 diabetes in the Finnish Diabetes Prevention Study
- 2017
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Wide-scale profiling technologies including metabolomics broaden the possibility of novel discoveries related to the pathogenesis of type 2 diabetes (T2D). By applying non-targeted metabolomics approach, we investigated here whether serum metabolite profile predicts T2D in a well-characterized study population with impaired glucose tolerance by examining two groups of individuals who took part in the Finnish Diabetes Prevention Study (DPS); those who either early developed T2D (n = 96) or did not convert to T2D within the 15-year follow-up (n = 104). Several novel metabolites were associated with lower likelihood of developing T2D, including indole and lipid related metabolites. Higher indolepropionic acid was associated with reduced likelihood of T2D in the DPS. Interestingly, in those who remained free of T2D, indolepropionic acid and various lipid species were associated with better insulin secretion and sensitivity, respectively. Furthermore, these metabolites were negatively correlated with low-grade inflammation. We replicated the association between indolepropionic acid and T2D risk in one Finnish and one Swedish population. We suggest that indolepropionic acid, a gut microbiota-produced metabolite, is a potential biomarker for the development of T2D that may mediate its protective effect by preservation of alpha-cell function. Novel lipid metabolites associated with T2D may exert their effects partly through enhancing insulin sensitivity.
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| 24. |
- Gericke, Sabrina Maria, et al.
(författare)
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In Situ H2 Reduction of Al2O3-Supported Ni- and Mo-Based Catalysts
- 2022
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Ingår i: Catalysts. - : MDPI. - 2073-4344. ; 12:7
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Tidskriftsartikel (refereegranskat)abstract
- Nickel (Ni)-promoted Molybdenum (Mo)-based catalysts are used for hydrotreatment processes in the chemical industry where the catalysts are exposed to high-pressure H2 at elevated temperature. In this environment, the catalyst transforms into the active phase, which involves the reduction of the oxide. Here, we report on the first in situ study on the reduction of alumina supported Ni- and Mo-based catalysts in 1 mbar H2 using ambient-pressure X-ray photoelectron spectroscopy (APXPS). The study confirms that mixing Ni and Mo lowers the reduction temperature of both Ni- and Mo-oxide as compared to the monometallic catalysts and shows that the MoO3 reduction starts at a lower temperature than the reduction of NiO in NiMo/Al2O3 catalysts. Additionally, the reduction of Ni and Mo foil was directly compared to the reduction of the Al2O3-supported catalysts and it was observed that the reduction of the supported catalysts is more gradual than the reduction of the foils, indicating a strong interaction between the Ni/Mo and the alumina support. © 2022 by the authors.
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| 25. |
- Hori, Yasunori, et al.
(författare)
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The Discovery and Follow-up of Four Transiting Short-period Sub-Neptunes Orbiting M Dwarfs
- 2024
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Ingår i: Astronomical Journal. - 1538-3881 .- 0004-6256. ; 167:6
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Tidskriftsartikel (refereegranskat)abstract
- Sub-Neptunes with radii of 2-3 R ⊕ are intermediate in size between rocky planets and Neptune-sized planets. The orbital properties and bulk compositions of transiting sub-Neptunes provide clues to the formation and evolution of close-in small planets. In this paper, we present the discovery and follow-up of four sub-Neptunes orbiting M dwarfs (TOI-782, TOI-1448, TOI-2120, and TOI-2406), three of which were newly validated by ground-based follow-up observations and statistical analyses. TOI-782 b, TOI-1448 b, TOI-2120 b, and TOI-2406 b have radii of R p = 2.740 − 0.079 + 0.082 R ⊕ , 2.769 − 0.068 + 0.073 R ⊕ , 2.120 ± 0.067 R ⊕, and 2.830 − 0.066 + 0.068 R ⊕ and orbital periods of P = 8.02, 8.11, 5.80, and 3.08 days, respectively. Doppler monitoring with the Subaru/InfraRed Doppler instrument led to 2σ upper limits on the masses of <19.1 M ⊕, <19.5 M ⊕, <6.8 M ⊕, and <15.6 M ⊕ for TOI-782 b, TOI-1448 b, TOI-2120 b, and TOI-2406 b, respectively. The mass-radius relationship of these four sub-Neptunes testifies to the existence of volatile material in their interiors. These four sub-Neptunes, which are located above the so-called “radius valley,” are likely to retain a significant atmosphere and/or an icy mantle on the core, such as a water world. We find that at least three of the four sub-Neptunes (TOI-782 b, TOI-2120 b, and TOI-2406 b), orbiting M dwarfs older than 1 Gyr, are likely to have eccentricities of e ∼ 0.2-0.3. The fact that tidal circularization of their orbits is not achieved over 1 Gyr suggests inefficient tidal dissipation in their interiors.
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