| 1. |
- 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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| 2. |
- Scott, Robert A., et al.
(författare)
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Large-scale association analyses identify new loci influencing glycemic traits and provide insight into the underlying biological pathways
- 2012
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 44:9, s. 991-1005
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Tidskriftsartikel (refereegranskat)abstract
- Through genome-wide association meta-analyses of up to 133,010 individuals of European ancestry without diabetes, including individuals newly genotyped using the Metabochip, we have increased the number of confirmed loci influencing glycemic traits to 53, of which 33 also increase type 2 diabetes risk (q < 0.05). Loci influencing fasting insulin concentration showed association with lipid levels and fat distribution, suggesting impact on insulin resistance. Gene-based analyses identified further biologically plausible loci, suggesting that additional loci beyond those reaching genome-wide significance are likely to represent real associations. This conclusion is supported by an excess of directionally consistent and nominally significant signals between discovery and follow-up studies. Functional analysis of these newly discovered loci will further improve our understanding of glycemic control.
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| 3. |
- Roy, Sushmita, et al.
(författare)
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Identification of functional elements and regulatory circuits by Drosophila modENCODE.
- 2010
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Ingår i: Science (New York, N.Y.). - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 330:6012, s. 1787-1797
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Tidskriftsartikel (refereegranskat)abstract
- To gain insight into how genomic information is translated into cellular and developmental programs, the Drosophila model organism Encyclopedia of DNA Elements (modENCODE) project is comprehensively mapping transcripts, histone modifications, chromosomal proteins, transcription factors, replication proteins and intermediates, and nucleosome properties across a developmental time course and in multiple cell lines. We have generated more than 700 data sets and discovered protein-coding, noncoding, RNA regulatory, replication, and chromatin elements, more than tripling the annotated portion of the Drosophila genome. Correlated activity patterns of these elements reveal a functional regulatory network, which predicts putative new functions for genes, reveals stage- and tissue-specific regulators, and enables gene-expression prediction. Our results provide a foundation for directed experimental and computational studies in Drosophila and related species and also a model for systematic data integration toward comprehensive genomic and functional annotation.
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| 4. |
- Chasman, Daniel I., et al.
(författare)
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Integration of genome-wide association studies with biological knowledge identifies six novel genes related to kidney function
- 2012
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 21:24, s. 5329-5343
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Tidskriftsartikel (refereegranskat)abstract
- In conducting genome-wide association studies (GWAS), analytical approaches leveraging biological information may further understanding of the pathophysiology of clinical traits. To discover novel associations with estimated glomerular filtration rate (eGFR), a measure of kidney function, we developed a strategy for integrating prior biological knowledge into the existing GWAS data for eGFR from the CKDGen Consortium. Our strategy focuses on single nucleotide polymorphism (SNPs) in genes that are connected by functional evidence, determined by literature mining and gene ontology (GO) hierarchies, to genes near previously validated eGFR associations. It then requires association thresholds consistent with multiple testing, and finally evaluates novel candidates by independent replication. Among the samples of European ancestry, we identified a genome-wide significant SNP in FBXL20 (P 5.6 10(9)) in meta-analysis of all available data, and additional SNPs at the INHBC, LRP2, PLEKHA1, SLC3A2 and SLC7A6 genes meeting multiple-testing corrected significance for replication and overall P-values of 4.5 10(4)2.2 10(7). Neither the novel PLEKHA1 nor FBXL20 associations, both further supported by association with eGFR among African Americans and with transcript abundance, would have been implicated by eGFR candidate gene approaches. LRP2, encoding the megalin receptor, was identified through connection with the previously known eGFR gene DAB2 and extends understanding of the megalin system in kidney function. These findings highlight integration of existing genome-wide association data with independent biological knowledge to uncover novel candidate eGFR associations, including candidates lacking known connections to kidney-specific pathways. The strategy may also be applicable to other clinical phenotypes, although more testing will be needed to assess its potential for discovery in general.
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| 5. |
- Craddock, Nick, et al.
(författare)
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Genome-wide association study of CNVs in 16,000 cases of eight common diseases and 3,000 shared controls
- 2010
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 464:7289, s. 713-720
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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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| 6. |
- Lembrechts, Jonas J., et al.
(författare)
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Global maps of soil temperature
- 2022
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Ingår i: Global Change Biology. - : Wiley. - 1354-1013 .- 1365-2486. ; 28:9, s. 3110-3144
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Tidskriftsartikel (refereegranskat)abstract
- Research in global change ecology relies heavily on global climatic grids derived from estimates of air temperature in open areas at around 2m above the ground. These climatic grids do not reflect conditions below vegetation canopies and near the ground surface, where critical ecosystem functions occur and most terrestrial species reside. Here, we provide global maps of soil temperature and bioclimatic variables at a 1-km2 resolution for 0–5 and 5–15cm soil depth. These maps were created by calculating the difference (i.e. offset) between in situ soil temperature measurements, based on time series from over 1200 1-km2 pixels (summarized from 8519 unique temperature sensors) across all the world's major terrestrial biomes, and coarse-grained air temperature estimates from ERA5-Land (an atmospheric reanalysis by the European Centre for Medium-Range Weather Forecasts). We show that mean annual soil temperature differs markedly from the corresponding gridded air temperature, by up to 10°C (mean=3.0±2.1°C), with substantial variation across biomes and seasons. Over the year, soils in cold and/or dry biomes are substantially warmer (+3.6±2.3°C) than gridded air temperature, whereas soils in warm and humid environments are on average slightly cooler (−0.7±2.3°C). The observed substantial and biome-specific offsets emphasize that the projected impacts of climate and climate change on near-surface biodiversity and ecosystem functioning are inaccurately assessed when air rather than soil temperature is used, especially in cold environments. The global soil-related bioclimatic variables provided here are an important step forward for any application in ecology and related disciplines. Nevertheless, we highlight the need to fill remaining geographic gaps by collecting more in situ measurements of microclimate conditions to further enhance the spatiotemporal resolution of global soil temperature products for ecological applications.
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| 7. |
- Parsa, Afshin, et al.
(författare)
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Common Variants in Mendelian Kidney Disease Genes and Their Association with Renal Function
- 2013
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Ingår i: Journal of the American Society of Nephrology. - 1046-6673 .- 1533-3450. ; 24:12, s. 2105-2117
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Tidskriftsartikel (refereegranskat)abstract
- Many common genetic variants identified by genome-wide association studies for complex traits map to genes previously linked to rare inherited Mendelian disorders. A systematic analysis of common single-nucleotide polymorphisms (SNPs) in genes responsible for Mendelian diseases with kidney phenotypes has not been performed. We thus developed a comprehensive database of genes for Mendelian kidney conditions and evaluated the association between common genetic variants within these genes and kidney function in the general population. Using the Online Mendelian Inheritance in Man database, we identified 731 unique disease entries related to specific renal search terms and confirmed a kidney phenotype in 218 of these entries, corresponding to mutations in 258 genes. We interrogated common SNPs (minor allele frequency >5%) within these genes for association with the estimated GFR in 74,354 European-ancestry participants from the CKDGen Consortium. However, the top four candidate SNPs (rs6433115 at LRP2, rs1050700 at TSC1, rs249942 at PALB2, and rs9827843 at ROBO2) did not achieve significance in a stage 2 meta-analysis performed in 56,246 additional independent individuals, indicating that these common SNPs are not associated with estimated GFR. The effect of less common or rare variants in these genes on kidney function in the general population and disease-specific cohorts requires further research.
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| 8. |
- Pattaro, Cristian, et al.
(författare)
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Genome-Wide Association and Functional Follow-Up Reveals New Loci for Kidney Function
- 2012
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Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 8:3, s. e1002584-
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Tidskriftsartikel (refereegranskat)abstract
- Chronic kidney disease (CKD) is an important public health problem with a genetic component. We performed genomewide association studies in up to 130,600 European ancestry participants overall, and stratified for key CKD risk factors. We uncovered 6 new loci in association with estimated glomerular filtration rate (eGFR), the primary clinical measure of CKD, in or near MPPED2, DDX1, SLC47A1, CDK12, CASP9, and INO80. Morpholino knockdown of mpped2 and casp9 in zebrafish embryos revealed podocyte and tubular abnormalities with altered dextran clearance, suggesting a role for these genes in renal function. By providing new insights into genes that regulate renal function, these results could further our understanding of the pathogenesis of CKD.
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| 9. |
- Kanai, M, et al.
(författare)
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- 2023
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swepub:Mat__t
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| 10. |
- Abolfathi, Bela, et al.
(författare)
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The Fourteenth Data Release of the Sloan Digital Sky Survey : First Spectroscopic Data from the Extended Baryon Oscillation Spectroscopic Survey and from the Second Phase of the Apache Point Observatory Galactic Evolution Experiment
- 2018
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Ingår i: Astrophysical Journal Supplement Series. - : IOP Publishing Ltd. - 0067-0049 .- 1538-4365. ; 235:2
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Tidskriftsartikel (refereegranskat)abstract
- The fourth generation of the Sloan Digital Sky Survey (SDSS-IV) has been in operation since 2014 July. This paper describes the second data release from this phase, and the 14th from SDSS overall (making this Data Release Fourteen or DR14). This release makes the data taken by SDSS-IV in its first two years of operation (2014-2016 July) public. Like all previous SDSS releases, DR14 is cumulative, including the most recent reductions and calibrations of all data taken by SDSS since the first phase began operations in 2000. New in DR14 is the first public release of data from the extended Baryon Oscillation Spectroscopic Survey; the first data from the second phase of the Apache Point Observatory (APO) Galactic Evolution Experiment (APOGEE-2), including stellar parameter estimates from an innovative data-driven machine-learning algorithm known as "The Cannon"; and almost twice as many data cubes from the Mapping Nearby Galaxies at APO (MaNGA) survey as were in the previous release (N = 2812 in total). This paper describes the location and format of the publicly available data from the SDSS-IV surveys. We provide references to the important technical papers describing how these data have been taken (both targeting and observation details) and processed for scientific use. The SDSS web site (www.sdss.org) has been updated for this release and provides links to data downloads, as well as tutorials and examples of data use. SDSS-IV is planning to continue to collect astronomical data until 2020 and will be followed by SDSS-V.
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| 11. |
- Adewumi, Oluseun, et al.
(författare)
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Characterization of human embryonic stem cell lines by the International Stem Cell Initiative
- 2007
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Ingår i: Nature Biotechnology. - : Springer Science and Business Media LLC. - 1087-0156 .- 1546-1696. ; 25:7, s. 803-816
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Tidskriftsartikel (refereegranskat)abstract
- The International Stem Cell Initiative characterized 59 human embryonic stem cell lines from 17 laboratories worldwide. Despite diverse genotypes and different techniques used for derivation and maintenance, all lines exhibited similar expression patterns for several markers of human embryonic stem cells. They expressed the glycolipid antigens SSEA3 and SSEA4, the keratan sulfate antigens TRA-1-60, TRA-1-81, GCTM2 and GCT343, and the protein antigens CD9, Thy1 (also known as CD90), tissue- nonspecific alkaline phosphatase and class 1 HLA, as well as the strongly developmentally regulated genes NANOG, POU5F1 (formerly known as OCT4), TDGF1, DNMT3B, GABRB3 and GDF3. Nevertheless, the lines were not identical: differences in expression of several lineage markers were evident, and several imprinted genes showed generally similar allele-specific expression patterns, but some gene-dependent variation was observed. Also, some female lines expressed readily detectable levels of XIST whereas others did not. No significant contamination of the lines with mycoplasma, bacteria or cytopathic viruses was detected.
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| 12. |
- Aguado, D. S., et al.
(författare)
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The Fifteenth Data Release of the Sloan Digital Sky Surveys : First Release of MaNGA-derived Quantities, Data Visualization Tools, and Stellar Library
- 2019
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Ingår i: Astrophysical Journal Supplement Series. - : Institute of Physics Publishing (IOPP). - 0067-0049 .- 1538-4365. ; 240:2
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Tidskriftsartikel (refereegranskat)abstract
- Twenty years have passed since first light for the Sloan Digital Sky Survey (SDSS). Here, we release data taken by the fourth phase of SDSS (SDSS-IV) across its first three years of operation (2014 July-2017 July). This is the third data release for SDSS-IV, and the 15th from SDSS (Data Release Fifteen; DR15). New data come from MaNGA-we release 4824 data cubes, as well as the first stellar spectra in the MaNGA Stellar Library (MaStar), the first set of survey-supported analysis products (e.g., stellar and gas kinematics, emission-line and other maps) from the MaNGA Data Analysis Pipeline, and a new data visualization and access tool we call "Marvin." The next data release, DR16, will include new data from both APOGEE-2 and eBOSS; those surveys release no new data here, but we document updates and corrections to their data processing pipelines. The release is cumulative; it also includes the most recent reductions and calibrations of all data taken by SDSS since first light. In this paper, we describe the location and format of the data and tools and cite technical references describing how it was obtained and processed. The SDSS website (www.sdss.org) has also been updated, providing links to data downloads, tutorials, and examples of data use. Although SDSS-IV will continue to collect astronomical data until 2020, and will be followed by SDSS-V (2020-2025), we end this paper by describing plans to ensure the sustainability of the SDSS data archive for many years beyond the collection of data.
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| 13. |
- Blanton, Michael R., et al.
(författare)
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Sloan Digital Sky Survey IV : Mapping the Milky Way, Nearby Galaxies, and the Distant Universe
- 2017
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Ingår i: Astronomical Journal. - : IOP Publishing Ltd. - 0004-6256 .- 1538-3881. ; 154:1
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Tidskriftsartikel (refereegranskat)abstract
- We describe the Sloan Digital Sky Survey IV (SDSS-IV), a project encompassing three major spectroscopic programs. The Apache Point Observatory Galactic Evolution Experiment 2 (APOGEE-2) is observing hundreds of thousands of Milky Way stars at high resolution and. high signal-to-noise ratios in the near-infrared. The Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey is obtaining spatially resolved spectroscopy for thousands of nearby galaxies (median z similar to 0.03). The extended Baryon Oscillation Spectroscopic Survey (eBOSS) is mapping the galaxy, quasar, and neutral gas distributions between z similar to 0.6 and 3.5 to constrain cosmology using baryon acoustic oscillations, redshift space distortions, and the shape of the power spectrum. Within eBOSS, we are conducting two major subprograms: the SPectroscopic IDentification of eROSITA Sources (SPIDERS), investigating X-ray AGNs. and galaxies in X-ray clusters, and the Time Domain Spectroscopic Survey (TDSS), obtaining spectra of variable sources. All programs use the 2.5 m Sloan Foundation Telescope at the. Apache Point Observatory; observations there began in Summer 2014. APOGEE-2 also operates a second near-infrared spectrograph at the 2.5 m du Pont Telescope at Las Campanas Observatory, with observations beginning in early 2017. Observations at both facilities are scheduled to continue through 2020. In keeping with previous SDSS policy, SDSS-IV provides regularly scheduled public data releases; the first one, Data Release 13, was made available in 2016 July.
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| 14. |
- Fong, Wen-fai, et al.
(författare)
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Short GRB Host Galaxies. I. Photometric and Spectroscopic Catalogs, Host Associations, and Galactocentric Offsets
- 2022
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 940:1
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Tidskriftsartikel (refereegranskat)abstract
- We present a comprehensive optical and near-infrared census of the fields of 90 short gamma-ray bursts (GRBs) discovered in 2005–2021, constituting all short GRBs for which host galaxy associations are feasible (≈60% of the total Swift short GRB population). We contribute 274 new multi-band imaging observations across 58 distinct GRBs and 26 spectra of their host galaxies. Supplemented by literature and archival survey data, the catalog contains 542 photometric and 42 spectroscopic data sets. The photometric catalog reaches 3σ depths of ≳24–27 mag and ≳23–26 mag for the optical and near-infrared bands, respectively. We identify host galaxies for 84 bursts, in which the most robust associations make up 56% (50/90) of events, while only a small fraction, 6.7%, have inconclusive host associations. Based on new spectroscopy, we determine 18 host spectroscopic redshifts with a range of z ≈ 0.15–1.5 and find that ≈23%–41% of Swift short GRBs originate from z > 1. We also present the galactocentric offset catalog for 84 short GRBs. Taking into account the large range of individual measurement uncertainties, we find a median of projected offset of ≈7.7 kpc, for which the bursts with the most robust associations have a smaller median of ≈4.8 kpc. Our catalog captures more high-redshift and low-luminosity hosts, and more highly offset bursts than previously found, thereby diversifying the population of known short GRB hosts and properties. In terms of locations and host luminosities, the populations of short GRBs with and without detectable extended emission are statistically indistinguishable. This suggests that they arise from the same progenitors, or from multiple progenitors, which form and evolve in similar environments. All of the data products are available on the Broadband Repository for Investigating Gamma-Ray Burst Host Traits website.
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| 15. |
- Heap, Graham A., et al.
(författare)
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HLA-DQA1-HLA-DRB1 variants confer susceptibility to pancreatitis induced by thiopurine immunosuppressants
- 2014
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 46:10, s. 1131-1134
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Tidskriftsartikel (refereegranskat)abstract
- Pancreatitis occurs in approximately 4% of patients treated with the thiopurines azathioprine or mercaptopurine. Its development is unpredictable and almost always leads to drug withdrawal. We identified patients with inflammatory bowel disease (IBD) who had developed pancreatitis within 3 months of starting these drugs from 168 sites around the world. After detailed case adjudication, we performed a genome-wide association study on 172 cases and 2,035 controls with IBD. We identified strong evidence of association within the class II HLA region, with the most significant association identified at rs2647087 (odds ratio 2.59, 95% confidence interval 2.07-3.26, P = 2 x 10(-16)). We replicated these findings in an independent set of 78 cases and 472 controls with IBD matched for drug exposure. Fine mapping of the H LA region identified association with the HLA-DQA1*02:01-HLA-DRB1*07:01 haplotype. Patients heterozygous at rs2647087 have a 9% risk of developing pancreatitis after administration of a thiopurine, whereas homozygotes have a 17% risk.
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| 16. |
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| 17. |
- Hosseinzadeh, Griffin, et al.
(författare)
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The Early Light Curve of SN 2023bee : Constraining Type Ia Supernova Progenitors the Apian Way
- 2023
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Ingår i: Astrophysical Journal Letters. - 2041-8205 .- 2041-8213. ; 953:1
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Tidskriftsartikel (refereegranskat)abstract
- We present very early photometric and spectroscopic observations of the Type Ia supernova (SN Ia) 2023bee, starting about 8 hr after the explosion, which reveal a strong excess in the optical and nearest UV (U and UVW1) bands during the first several days of explosion. This data set allows us to probe the nature of the binary companion of the exploding white dwarf and the conditions leading to its ignition. We find a good match to the Kasen model in which a main-sequence companion star stings the ejecta with a shock as they buzz past. Models of double detonations, shells of radioactive nickel near the surface, interaction with circumstellar material, and pulsational delayed detonations do not provide good matches to our light curves. We also observe signatures of unburned material, in the form of carbon absorption, in our earliest spectra. Our radio nondetections place a limit on the mass-loss rate from the putative companion that rules out a red giant but allows a main-sequence star. We discuss our results in the context of other similar SNe Ia in the literature.
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| 18. |
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| 19. |
- Lembrechts, Jonas J., et al.
(författare)
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SoilTemp : A global database of near-surface temperature
- 2020
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Ingår i: Global Change Biology. - : Wiley. - 1354-1013 .- 1365-2486. ; 26:11, s. 6616-6629
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Tidskriftsartikel (refereegranskat)abstract
- Current analyses and predictions of spatially explicit patterns and processes in ecology most often rely on climate data interpolated from standardized weather stations. This interpolated climate data represents long-term average thermal conditions at coarse spatial resolutions only. Hence, many climate-forcing factors that operate at fine spatiotemporal resolutions are overlooked. This is particularly important in relation to effects of observation height (e.g. vegetation, snow and soil characteristics) and in habitats varying in their exposure to radiation, moisture and wind (e.g. topography, radiative forcing or cold-air pooling). Since organisms living close to the ground relate more strongly to these microclimatic conditions than to free-air temperatures, microclimatic ground and near-surface data are needed to provide realistic forecasts of the fate of such organisms under anthropogenic climate change, as well as of the functioning of the ecosystems they live in. To fill this critical gap, we highlight a call for temperature time series submissions to SoilTemp, a geospatial database initiative compiling soil and near-surface temperature data from all over the world. Currently, this database contains time series from 7,538 temperature sensors from 51 countries across all key biomes. The database will pave the way toward an improved global understanding of microclimate and bridge the gap between the available climate data and the climate at fine spatiotemporal resolutions relevant to most organisms and ecosystem processes.
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| 20. |
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| 21. |
- Ni, Yuan Qi, et al.
(författare)
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Infant-phase reddening by surface Fe-peak elements in a normal type Ia supernova
- 2022
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Ingår i: Nature Astronomy. - : Springer Science and Business Media LLC. - 2397-3366. ; 6:5, s. 568-576
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Tidskriftsartikel (refereegranskat)abstract
- Type Ia supernovae are thermonuclear explosions of white dwarf stars. They play a central role in the chemical evolution of the Universe and are an important measure of cosmological distances. However, outstanding questions remain about their origins. Despite extensive efforts to obtain natal information from their earliest signals, observations have thus far failed to identify how the majority of them explode. Here, we present infant-phase detections of SN 2018aoz from a very low brightness of −10.5 AB absolute magnitude, revealing a hitherto unseen plateau in the B band that results in a rapid redward colour evolution between 1.0 and 12.4 hours after the estimated epoch of first light. The missing B-band flux is best explained by line-blanket absorption from Fe-peak elements in the outer 1% of the ejected mass. The observed B − V colour evolution of the supernova also matches the prediction from an over-density of Fe-peak elements in the same outer 1% of the ejected mass, whereas bluer colours are expected from a purely monotonic distribution of Fe-peak elements. The presence of excess nucleosynthetic material in the extreme outer layers of the ejecta points to enhanced surface nuclear burning or extended subsonic mixing processes in some normal type Ia SN explosions.
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| 22. |
- Ni, Yuan Qi, et al.
(författare)
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The Origin and Evolution of the Normal Type Ia SN 2018aoz with Infant-phase Reddening and Excess Emission
- 2023
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 946:1
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Tidskriftsartikel (refereegranskat)abstract
- SN 2018aoz is a Type Ia SN with a B-band plateau and excess emission in infant-phase light curves ≲1 day after the first light, evidencing an over-density of surface iron-peak elements as shown in our previous study. Here, we advance the constraints on the nature and origin of SN 2018aoz based on its evolution until the nebular phase. Near-peak spectroscopic features show that the SN is intermediate between two subtypes of normal Type Ia: core normal and broad line. The excess emission may be attributable to the radioactive decay of surface iron-peak elements as well as the interaction of ejecta with either the binary companion or a small torus of circumstellar material. Nebular-phase limits on Hα and He i favor a white dwarf companion, consistent with the small companion size constrained by the low early SN luminosity, while the absence of [O I] and He i disfavors a violent merger of the progenitor. Of the two main explosion mechanisms proposed to explain the distribution of surface iron-peak elements in SN 2018aoz, the asymmetric Chandrasekhar-mass explosion is less consistent with the progenitor constraints and the observed blueshifts of nebular-phase [Fe II] and [Ni II]. The helium-shell double-detonation explosion is compatible with the observed lack of C spectral features, but current 1D models are incompatible with the infant-phase excess emission, Bmax–Vmax color, and weak strength of nebular-phase [Ca II]. Although the explosion processes of SN 2018aoz still need to be more precisely understood, the same processes could produce a significant fraction of Type Ia SNe that appear to be normal after ∼1 day.
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| 23. |
- Stocchetti, Nino, et al.
(författare)
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Clinical applications of intracranial pressure monitoring in traumatic brain injury
- 2014
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Ingår i: Acta Neurochirurgica. - : Springer. - 0001-6268 .- 0942-0940. ; 156:8, s. 1615-1622
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Tidskriftsartikel (refereegranskat)abstract
- Intracranial pressure (ICP) monitoring has been for decades a cornerstone of traumatic brain injury (TBI) management. Nevertheless, in recent years, its usefulness has been questioned in several reports. A group of neurosurgeons and neurointensivists met to openly discuss, and provide consensus on, practical applications of ICP in severe adult TBI. A consensus conference was held in Milan on October 5, 2013, putting together neurosurgeons and intensivists with recognized expertise in treatment of TBI. Four topics have been selected and addressed in pro-con presentations: 1) ICP indications in diffuse brain injury, 2) cerebral contusions, 3) secondary decompressive craniectomy (DC), and 4) after evacuation of intracranial traumatic hematomas. The participants were asked to elaborate on the existing published evidence (without a systematic review) and their personal clinical experience. Based on the presentations and discussions of the conference, some drafts were circulated among the attendants. After remarks and further contributions were collected, a final document was approved by the participants. The group made the following recommendations: 1) in comatose TBI patients, in case of normal computed tomography (CT) scan, there is no indication for ICP monitoring; 2) ICP monitoring is indicated in comatose TBI patients with cerebral contusions in whom the interruption of sedation to check neurological status is dangerous and when the clinical examination is not completely reliable. The probe should be positioned on the side of the larger contusion; 3) ICP monitoring is generally recommended following a secondary DC in order to assess the effectiveness of DC in terms of ICP control and guide further therapy; 4) ICP monitoring after evacuation of an acute supratentorial intracranial hematoma should be considered for salvageable patients at increased risk of intracranial hypertension with particular perioperative features.
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| 24. |
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The Seventeenth Data Release of the Sloan Digital Sky Surveys : Complete Release of MaNGA, MaStar, and APOGEE-2 Data
- 2022
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Ingår i: Astrophysical Journal Supplement Series. - : Institute of Physics (IOP). - 0067-0049 .- 1538-4365. ; 259:2
-
Tidskriftsartikel (refereegranskat)abstract
- This paper documents the seventeenth data release (DR17) from the Sloan Digital Sky Surveys; the fifth and final release from the fourth phase (SDSS-IV). DR17 contains the complete release of the Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey, which reached its goal of surveying over 10,000 nearby galaxies. The complete release of the MaNGA Stellar Library accompanies this data, providing observations of almost 30,000 stars through the MaNGA instrument during bright time. DR17 also contains the complete release of the Apache Point Observatory Galactic Evolution Experiment 2 survey that publicly releases infrared spectra of over 650,000 stars. The main sample from the Extended Baryon Oscillation Spectroscopic Survey (eBOSS), as well as the subsurvey Time Domain Spectroscopic Survey data were fully released in DR16. New single-fiber optical spectroscopy released in DR17 is from the SPectroscipic IDentification of ERosita Survey subsurvey and the eBOSS-RM program. Along with the primary data sets, DR17 includes 25 new or updated value-added catalogs. This paper concludes the release of SDSS-IV survey data. SDSS continues into its fifth phase with observations already underway for the Milky Way Mapper, Local Volume Mapper, and Black Hole Mapper surveys.
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| 25. |
- Wang, Anqi, et al.
(författare)
-
Characterizing prostate cancer risk through multi-ancestry genome-wide discovery of 187 novel risk variants
- 2023
-
Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 55:12, s. 2065-2074
-
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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| 26. |
- Niemi, MEK, et al.
(författare)
-
- 2021
-
swepub:Mat__t
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| 27. |
- Adare, A., et al.
(författare)
-
Charged-pion cross sections and double-helicity asymmetries in polarized p plus p collisions at root s=200 GeV
- 2015
-
Ingår i: Physical Review D (Particles, Fields, Gravitation and Cosmology). - 1550-2368. ; 91:3
-
Tidskriftsartikel (refereegranskat)abstract
- We present midrapidity charged-pion invariant cross sections, the ratio of the pi(-) to pi(+) cross sections and the charge-separated double-spin asymmetries in polarized p + p collisions at root s = p + 200 GeV. While the cross section measurements are consistent within the errors of next-to-leading-order (NLO) perturbative quantum chromodynamics predictions (pQCD), the same calculations overestimate the ratio of the charged-pion cross sections. This discrepancy arises from the cancellation of the substantial systematic errors associated with the NLO-pQCD predictions in the ratio and highlights the constraints these data will place on flavor-dependent pion fragmentation functions. The charge-separated pion asymmetries presented here sample an x range of similar to 0.03-0.16 and provide unique information on the sign of the gluon-helicity distribution.
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| 28. |
- Adare, A., et al.
(författare)
-
Cold-Nuclear-Matter Effects on Heavy-Quark Production at Forward and Backward Rapidity in d + Au Collisions at root s(NN) = GeV
- 2014
-
Ingår i: Physical Review Letters. - 1079-7114. ; 112:25
-
Tidskriftsartikel (refereegranskat)abstract
- The PHENIX experiment has measured open heavy-flavor production via semileptonic decay over the transverse momentum range 1 < p(T) < 6 GeV/c at forward and backward rapidity (1.4 < vertical bar y vertical bar < 2.0) in d + Au and p + p collisions at root s(NN) = 200 GeV. In central d + Au collisions, relative to the yield in p + p collisions scaled by the number of binary nucleon-nucleon collisions, a suppression is observed at forward rapidity (in the d-going direction) and an enhancement at backward rapidity (in the Au-going direction). Predictions using nuclear-modified-parton-distribution functions, even with additional nuclear-p(T) broadening, cannot simultaneously reproduce the data at both rapidity ranges, which implies that these models are incomplete and suggests the possible importance of final-state interactions in the asymmetric d + Au collision system. These results can be used to probe cold-nuclear-matter effects, which may significantly affect heavy-quark production, in addition to helping constrain the magnitude of charmonia-breakup effects in nuclear matter.
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| 29. |
- Adare, A., et al.
(författare)
-
Cross Section and Parity-Violating Spin Asymmetries of W-+/- Boson Production in Polarized p plus p Collisions at root s=500 Gev
- 2011
-
Ingår i: Physical Review Letters. - 1079-7114. ; 106:6
-
Tidskriftsartikel (refereegranskat)abstract
- Large parity-violating longitudinal single-spin asymmetries A(L)(e+) = 0.86(-0.14)(+0.30) and Ae(L)(e-) = 0.88(-0.71)(+0.12) are observed for inclusive high transverse momentum electrons and positrons in polarized p + p collisions at a center-of-mass energy of root s = 500 GeV with the PHENIX detector at RHIC. These e(+/-) come mainly from the decay of W-+/- and Z(0) bosons, and their asymmetries directly demonstrate parity violation in the couplings of the W-+/- to the light quarks. The observed electron and positron yields were used to estimate W-+/- boson production cross sections for the e(+/-) channels of sigma(pp -> W+X) X BR(W+ -> e(+) nu(e)) = 144.1 +/- 21.2(stat)(-10.3)(+3.4)(syst) +/- 21.6(norm) pb, and sigma(pp -> W-X) X BR(W- -> e(-) (nu) over bar (e)) = 3.17 +/- 12.1(stat)(-8.2)(+10.1)(syst) +/- 4.8(norm) pb.
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| 30. |
- Adare, A., et al.
(författare)
-
Double-spin asymmetry of electrons from heavy-flavor decays in p plus p collisions at root s=200 GeV
- 2013
-
Ingår i: Physical Review D (Particles, Fields, Gravitation and Cosmology). - 1550-2368. ; 87:1
-
Tidskriftsartikel (refereegranskat)abstract
- We report on the first measurement of the double-spin asymmetry, A(LL), of electrons from the decays of hadrons containing heavy flavor in longitudinally polarized p + p collisions at root s = 200 GeV for p(T) = 0.5 to 3.0 GeV/c. The asymmetry was measured at midrapidity (vertical bar eta vertical bar < 0.35) with the PHENIX detector at the Relativistic Heavy Ion Collider. The measured asymmetries are consistent with zero within the statistical errors. We obtained a constraint for the polarized gluon distribution in the proton of vertical bar Delta g/g(log(10)(x) = -1.6(-0.4)(+0.5), mu = m(T)(c)vertical bar(2) < 0.030 (1 sigma) based on a leading-order perturbative quantum chromodynamics model, using the measured asymmetry. DOI: 10.1103/PhysRevD.87.012011
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| 31. |
- Adare, A., et al.
(författare)
-
gamma (1S+2S+3S) production in d plus Au and p plus p collisions at root s(NN)=200 GeV and cold-nuclear-matter effects
- 2013
-
Ingår i: Physical Review C (Nuclear Physics). - 0556-2813. ; 87:4
-
Tidskriftsartikel (refereegranskat)abstract
- The three gamma states, gamma (1S + 2S + 3S), are measured in d + Au and p + p collisions at root s(NN) = 200 GeV and rapidities 1.2 < vertical bar y vertical bar < 2.2 by the PHENIX experiment at the Relativistic Heavy Ion Collider. Cross sections for the inclusive gamma (1S + 2S + 3S) production are obtained. The inclusive yields per binary collision for d + Au collisions relative to those in p + p collisions (R-dAu) are found to be 0.62 +/- 0.26 (stat) +/- 0.13 (syst) in the gold-going direction and 0.91 +/- 0.33 (stat) +/- 0.16 (syst) in the deuteron-going direction. The measured results are compared to a nuclear-shadowing model, EPS09 [Eskola et al., J. High Energy Phys. 04 (2009) 065], combined with a final-state breakup cross section, sigma(br), and compared to lower energy p + A results. We also compare the results to the PHENIX J/psi results [Adare et al., Phys. Rev. Lett. 107, 142301 (2011)]. The rapidity dependence of the observed gamma suppression is consistent with lower energy p + A measurements. DOI: 10.1103/PhysRevC.87.044909
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| 32. |
- Adare, A., et al.
(författare)
-
Inclusive double-helicity asymmetries in neutral-pion and eta-meson production in + collisions at root s=200 GeV
- 2014
-
Ingår i: Physical Review D (Particles, Fields, Gravitation and Cosmology). - 1550-2368. ; 90:1
-
Tidskriftsartikel (refereegranskat)abstract
- Results are presented from data recorded in 2009 by the PHENIX experiment at the Relativistic Heavy Ion Collider for the double-longitudinal spin asymmetry, A(LL), for pi(0) and eta production in root s = 200 GeV polarized p + p collisions. Comparison of the pi(0) results with different theory expectations based on fits of other published data showed a preference for small positive values of gluon polarization, Delta G, in the proton in the probed Bjorken x range. The effect of adding the new 2009 pi(0) data to a recent global analysis of polarized scattering data is also shown, resulting in a best fit Delta G(DSSV)([0.05,0.2]) = 0.06(-0.15)(+0.11) in the range 0.05 < x < 0.2, with the uncertainty at Delta chi(2) = 9 when considering only statistical experimental uncertainties. Shifting the PHENIX data points by their systematic uncertainty leads to a variation of the best-fit value of Delta G(DSSV)([0.05,0.2]) between 0.02 and 0.12, demonstrating the need for full treatment of the experimental systematic uncertainties in future global analyses.
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| 33. |
- Adare, A., et al.
(författare)
-
Low-mass vector-meson production at forward rapidity in p plus p collisions at root s=200 GeV
- 2014
-
Ingår i: Physical Review D (Particles, Fields, Gravitation and Cosmology). - 1550-2368. ; 90:5
-
Tidskriftsartikel (refereegranskat)abstract
- The PHENIX experiment at the Relativistic Heavy Ion Collider has measured low-mass vector-meson ,omega, rho, and phi, production through the dimuon decay channel at forward rapidity (1.2 < vertical bar y vertical bar < 2.2) in p + p collisions at root s = 200 GeV. The differential cross sections for these mesons are measured as a function of both p(T) and rapidity. We also report the integrated differential cross sections over 1 < p(T) < 7 GeV/c and 1.2 < vertical bar y vertical bar < 2.2: d sigma/dy(omega + rho rho -> mu mu) = 80 +/- 6(stat) +/- 12(syst)nb and d sigma/dy(phi -> mu mu) = 27 +/- 3(stat) +/- 4(syst)nb. These results are compared with midrapidity measurements and calculations.
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| 34. |
- Adare, A, et al.
(författare)
-
Measurement of Long-Range Angular Correlation and Quadrupole Anisotropy of Pions and (Anti)Protons in Central d+Au Collisions at sqrt[s_{NN}]=200 GeV.
- 2015
-
Ingår i: Physical Review Letters. - 1079-7114. ; 114:19
-
Tidskriftsartikel (refereegranskat)abstract
- We present azimuthal angular correlations between charged hadrons and energy deposited in calorimeter towers in central d+Au and minimum bias p+p collisions at sqrt[s_{NN}]=200 GeV. The charged hadron is measured at midrapidity |η|<0.35, and the energy is measured at large rapidity (-3.7<η<-3.1, Au-going direction). An enhanced near-side angular correlation across |Δη|>2.75 is observed in d+Au collisions. Using the event plane method applied to the Au-going energy distribution, we extract the anisotropy strength v_{2} for inclusive charged hadrons at midrapidity up to p_{T}=4.5 GeV/c. We also present the measurement of v_{2} for identified π^{±} and (anti)protons in central d+Au collisions, and observe a mass-ordering pattern similar to that seen in heavy-ion collisions. These results are compared with viscous hydrodynamic calculations and measurements from p+Pb at sqrt[s_{NN}]=5.02 TeV. The magnitude of the mass ordering in d+Au is found to be smaller than that in p+Pb collisions, which may indicate smaller radial flow in lower energy d+Au collisions.
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| 35. |
- Adare, A., et al.
(författare)
-
Measurements of Elliptic and Triangular Flow in High-Multiplicity He-3 + Au Collisions at root s(NN)=200 GeV
- 2015
-
Ingår i: Physical Review Letters. - 1079-7114. ; 115:14
-
Tidskriftsartikel (refereegranskat)abstract
- We present the first measurement of elliptic (v(2)) and triangular (v(3)) flow in high-multiplicity He-3 + Au collisions at root s(NN) = 200 GeV. Two-particle correlations, where the particles have a large separation in pseudorapidity, are compared in He-3 + Au and in p + p collisions and indicate that collective effects dominate the second and third Fourier components for the correlations observed in the He-3 + Au system. The collective behavior is quantified in terms of elliptic v(2) and triangular v(3) anisotropy coefficients measured with respect to their corresponding event planes. The v(2) values are comparable to those previously measured in d + Au collisions at the same nucleon-nucleon center-of-mass energy. Comparisons with various theoretical predictions are made, including to models where the hot spots created by the impact of the three He-3 nucleons on the Au nucleus expand hydrodynamically to generate the triangular flow. The agreement of these models with data may indicate the formation of low-viscosity quark-gluon plasma even in these small collision systems.
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| 36. |
- Adare, A., et al.
(författare)
-
Search for dark photons from neutral meson decays in p plus p and d plus Au collisions at root s(NN)=200 GeV
- 2015
-
Ingår i: Physical Review C (Nuclear Physics). - 0556-2813. ; 91:3
-
Tidskriftsartikel (refereegranskat)abstract
- The standard model (SM) of particle physics is spectacularly successful, yet the measured value of the muon anomalous magnetic moment (g - 2)mu deviates from SM calculations by 3.6 sigma. Several theoretical models attribute this to the existence of a "dark photon," an additional U(1) gauge boson, which is weakly coupled to ordinary photons. The PHENIX experiment at the Relativistic Heavy Ion Collider has searched for a dark photon, U, in pi(0), eta -> gamma e(+)e(-) decays and obtained upper limits of O(2 x 10(-6)) on U-gamma mixing at 90% C.L. for the mass range 30 < m(U) < 90 MeV/c(2). Combined with other experimental limits, the remaining region in the U-gamma mixing parameter space that can explain the (g - 2)(mu) deviation from its SM value is nearly completely excluded at the 90% confidence level, with only a small region of 29 < m(U) < 32 MeV/c(2) remaining.
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| 37. |
- Backeljauw, Philippe F., et al.
(författare)
-
Challenges in the care of individuals with severe primary insulin-like growth factor-I deficiency (SPIGFD): an international, multi-stakeholder perspective
- 2023
-
Ingår i: Orphanet Journal of Rare Diseases. - : BMC. - 1750-1172. ; 18:1
-
Forskningsöversikt (refereegranskat)abstract
- Background Severe primary insulin-like growth factor-I (IGF-I) deficiency (SPIGFD) is a rare growth disorder characterized by short stature (standard deviation score [SDS] <= 3.0), low circulating concentrations of IGF-I (SDS <= 3.0), and normal or elevated concentrations of growth hormone (GH). Laron syndrome is the best characterized form of SPIGFD, caused by a defect in the GH receptor (GHR) gene. However, awareness of SPIGFD remains low, and individuals living with SPIGFD continue to face challenges associated with diagnosis, treatment and care. Objective To gather perspectives on the key challenges for individuals and families living with SPIGFD through a multi-stakeholder approach. By highlighting critical gaps in the awareness, diagnosis, and management of SPIGFD, this report aims to provide recommendations to improve care for people affected by SPIGFD globally. Methods An international group of clinical experts, researchers, and patient and caregiver representatives from the SPIGFD community participated in a virtual, half-day meeting to discuss key unmet needs and opportunities to improve the care of people living with SPIGFD. Results As a rare disorder, limited awareness and understanding of SPIGFD amongst healthcare professionals (HCPs) poses significant challenges in the diagnosis and treatment of those affected. Patients often face difficulties associated with receiving a formal diagnosis, delayed treatment initiation and limited access to appropriate therapy. This has a considerable impact on the physical health and quality of life for patients, highlighting a need for more education and clearer guidance for HCPs. Support from patient advocacy groups is valuable in helping patients and their families to find appropriate care. However, there remains a need to better understand the burden that SPIGFD has on individuals beyond height, including the impact on physical, emotional, and social wellbeing. Conclusions To address the challenges faced by individuals and families affected by SPIGFD, greater awareness of SPIGFD is needed within the healthcare community, and a consensus on best practice in the care of individuals affected by this condition. Continued efforts are also needed at a global level to challenge existing perceptions around SPIGFD, and identify solutions that promote equitable access to appropriate care.
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| 38. |
- Barna, Barnabas, et al.
(författare)
-
SN 2019muj-a well-observed Type Iax supernova that bridges the luminosity gap of the class
- 2021
-
Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 501:1, s. 1078-1099
-
Tidskriftsartikel (refereegranskat)abstract
- We present early-time (t < +50 d) observations of SN 2019muj (=ASASSN-19tr), one of the best-observed members of the peculiar SN Iax class. Ultraviolet and optical photometric and optical and near-infrared spectroscopic follow-up started from similar to 5 d before maximum light [t(max)(B) on 58707.8 MJD] and covers the photospheric phase. The early observations allow us to estimate the physical properties of the ejecta and characterize the possible divergence from a uniform chemical abundance structure. The estimated bolometric light-curve peaks at 1.05 x 10(42) erg s(-1) and indicates that only 0.031 M-circle dot of Ni-56 was produced, making SN 2019muj a moderate luminosity object in the Iax class with peak absolute magnitude of M-V = -16.4 mag. The estimated date of explosion is t(0) = 58698.2 MJD and implies a short rise time of t(rise) = 9.6 d in B band. We fit of the spectroscopic data by synthetic spectra, calculated via the radiative transfer code TARDIS. Adopting the partially stratified abundance template based on brighter SNe Iax provides a good match with SN 2019muj. However, without earlier spectra, the need for stratification cannot be stated in most of the elements, except carbon, which is allowed to appear in the outer layers only. SN 2019muj provides a unique opportunity to link extremely low-luminosity SNe Iax to well-studied, brighter SNe Iax.
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| 39. |
- Beecham, Ashley H, et al.
(författare)
-
Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis.
- 2013
-
Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 45:11, s. 1353-60
-
Tidskriftsartikel (refereegranskat)abstract
- Using the ImmunoChip custom genotyping array, we analyzed 14,498 subjects with multiple sclerosis and 24,091 healthy controls for 161,311 autosomal variants and identified 135 potentially associated regions (P < 1.0 × 10(-4)). In a replication phase, we combined these data with previous genome-wide association study (GWAS) data from an independent 14,802 subjects with multiple sclerosis and 26,703 healthy controls. In these 80,094 individuals of European ancestry, we identified 48 new susceptibility variants (P < 5.0 × 10(-8)), 3 of which we found after conditioning on previously identified variants. Thus, there are now 110 established multiple sclerosis risk variants at 103 discrete loci outside of the major histocompatibility complex. With high-resolution Bayesian fine mapping, we identified five regions where one variant accounted for more than 50% of the posterior probability of association. This study enhances the catalog of multiple sclerosis risk variants and illustrates the value of fine mapping in the resolution of GWAS signals.
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| 40. |
- Benatar, Michael, et al.
(författare)
-
Design of a randomized, placebo-controlled, phase 3 trial of tofersen initiated in clinically presymptomatic SOD1 variant carriers : the Atlas study
- 2022
-
Ingår i: Neurotherapeutics. - : Springer. - 1933-7213 .- 1878-7479. ; 19, s. 1248-1258
-
Tidskriftsartikel (refereegranskat)abstract
- Despite extensive research, amyotrophic lateral sclerosis (ALS) remains a progressive and invariably fatal neurodegenerative disease. Limited knowledge of the underlying causes of ALS has made it difficult to target upstream biological mechanisms of disease, and therapeutic interventions are usually administered relatively late in the course of disease. Genetic forms of ALS offer a unique opportunity for therapeutic development, as genetic associations may reveal potential insights into disease etiology. Genetic ALS may also be amenable to investigating earlier intervention given the possibility of identifying clinically presymptomatic, at-risk individuals with causative genetic variants. There is increasing evidence for a presymptomatic phase of ALS, with biomarker data from the Pre-Symptomatic Familial ALS (Pre-fALS) study showing that an elevation in blood neurofilament light chain (NfL) precedes phenoconversion to clinically manifest disease. Tofersen is an investigational antisense oligonucleotide designed to reduce synthesis of superoxide dismutase 1 (SOD1) protein through degradation of SOD1 mRNA. Informed by Pre-fALS and the tofersen clinical development program, the ATLAS study (NCT04856982) is designed to evaluate the impact of initiating tofersen in presymptomatic carriers of SOD1 variants associated with high or complete penetrance and rapid disease progression who also have biomarker evidence of disease activity (elevated plasma NfL). The ATLAS study will investigate whether tofersen can delay the emergence of clinically manifest ALS. To our knowledge, ATLAS is the first interventional trial in presymptomatic ALS and has the potential to yield important insights into the design and conduct of presymptomatic trials, identification, and monitoring of at-risk individuals, and future treatment paradigms in ALS.
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| 41. |
- Bose, Subhash, et al.
(författare)
-
ASASSN-15nx : A Luminous Type II Supernova with a Perfect Linear Decline
- 2018
-
Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 862:2
-
Tidskriftsartikel (refereegranskat)abstract
- We report a luminous Type II supernova, ASASSN-15nx, with a peak luminosity of M-v = -20 mag that is between those of typical core-collapse supernovae and super-luminous supernovae. The post-peak optical light curves show a long, linear decline with a steep slope of 2.5 mag (100 day)(-1) (i.e., an exponential decline in flux) through the end of observations at phase approximate to 260 day. In contrast, the light curves of hydrogen-rich supernovae (SNe II-P/L) always show breaks in their light curves at phase similar to 100 day, before settling onto Co-56 radioactive decay tails with a decline rate of about 1 mag (100 day)(-1). The spectra of ASASSN-15nx do not exhibit the narrow emission-line features characteristic of Type IIn SNe, which can have a wide variety of light-curve shapes usually attributed to strong interactions with a dense circumstellar medium (CSM). ASASSN-15nx has a number of spectroscopic peculiarities, including a relatively weak and triangular-shaped H alpha emission profile with no absorption component. The physical origin of these peculiarities is unclear, but the long and linear post-peak light curve without a break suggests a single dominant powering mechanism. Decay of a large amount of Ni-56 (M-Ni = 1.6 +/- 0.2 M-circle dot) can power the light curve of ASASSN-15nx, and the steep light-curve slope requires substantial gamma-ray escape from the ejecta, which is possible given a low-mass hydrogen envelope for the progenitor. Another possibility is strong CSM interactions powering the light curve, but the CSM needs to be sculpted to produce the unique light-curve shape and avoid producing SN IIn-like narrow emission lines.
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| 42. |
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| 43. |
- Christmas, Matthew, et al.
(författare)
-
Evolutionary constraint and innovation across hundreds of placental mammals
- 2023
-
Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 380:6643
-
Tidskriftsartikel (refereegranskat)abstract
- Zoonomia is the largest comparative genomics resource for mammals produced to date. By aligning genomes for 240 species, we identify bases that, when mutated, are likely to affect fitness and alter disease risk. At least 332 million bases (similar to 10.7%) in the human genome are unusually conserved across species (evolutionarily constrained) relative to neutrally evolving repeats, and 4552 ultraconserved elements are nearly perfectly conserved. Of 101 million significantly constrained single bases, 80% are outside protein-coding exons and half have no functional annotations in the Encyclopedia of DNA Elements (ENCODE) resource. Changes in genes and regulatory elements are associated with exceptional mammalian traits, such as hibernation, that could inform therapeutic development. Earth's vast and imperiled biodiversity offers distinctive power for identifying genetic variants that affect genome function and organismal phenotypes.
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| 44. |
- Conrad, Donald F., et al.
(författare)
-
Origins and functional impact of copy number variation in the human genome
- 2010
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 464:7289, s. 704-712
-
Tidskriftsartikel (refereegranskat)abstract
- Structural variations of DNA greater than 1 kilobase in size account for most bases that vary among human genomes, but are still relatively under-ascertained. Here we use tiling oligonucleotide microarrays, comprising 42 million probes, to generate a comprehensive map of 11,700 copy number variations (CNVs) greater than 443 base pairs, of which most (8,599) have been validated independently. For 4,978 of these CNVs, we generated reference genotypes from 450 individuals of European, African or East Asian ancestry. The predominant mutational mechanisms differ among CNV size classes. Retrotransposition has duplicated and inserted some coding and non-coding DNA segments randomly around the genome. Furthermore, by correlation with known trait-associated single nucleotide polymorphisms (SNPs), we identified 30 loci with CNVs that are candidates for influencing disease susceptibility. Despite this, having assessed the completeness of our map and the patterns of linkage disequilibrium between CNVs and SNPs, we conclude that, for complex traits, the heritability void left by genome-wide association studies will not be accounted for by common CNVs.
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| 45. |
- Covaciu, Lucian, 1964-
(författare)
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Intranasal Cooling for Cerebral Hypothermia Treatment
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The controlled lowering of core body temperature to 32°C to 34°C is defined as therapeutic hypothermia (TH). Therapeutic hypothermia has been shown to improve neurological outcome and survival in unconscious patients successfully resuscitated after cardiac arrest. Brain temperature is important for cerebral protection therefore methods for primarily cooling the brain have also been explored. This thesis focuses on the likelihood that intranasal cooling can induce, maintain and control cerebral hypothermia. The method uses bilaterally introduced intranasal balloons circulated with cold saline. Selective brain cooling induced with this method was effectively accomplished in pigs with normal circulation while no major disturbances in systemic circulation or physiological variables were recorded. The temperature gradients between brain and body could be maintained for at least six hours. Intranasal balloon catheters were used for therapeutic hypothermia initiation and maintenance during and after successful resuscitation in pigs. Temperature reduction was also obtained by combined intranasal cooling and intravenous ice-cold fluids with possible additional benefits in terms of physiologic stability after cardiac arrest. Rewarming was possible via the intranasal balloons. In these studies brain temperature was recorded invasively by temperature probes inserted in the brain. The fast changes in pig’s brain temperature could also be tracked by a non-invasive method. High-spatial resolution magnetic resonance spectroscopic imaging (MRSI) without internal reference showed a good association with direct invasive temperature monitoring. In addition the mapping of temperature changes during brain cooling was also possible. In awake and unsedated volunteers subjected to intranasal cooling brain temperature changes were followed by two MR techniques. Brain cooling was shown by the previously calibrated high-spatial resolution MRSI and by the phase-mapping method. Intranasal cooling reduced body temperature slightly. The volunteers remained alert during cooling, the physiological parameters stable, and no shivering was reported.
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| 46. |
- Cunningham, Anthony L., et al.
(författare)
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Immune Responses to a Recombinant Glycoprotein E Herpes Zoster Vaccine in Adults Aged 50 Years or Older
- 2018
-
Ingår i: Journal of Infectious Diseases. - : Oxford University Press. - 0022-1899 .- 1537-6613. ; 217:11, s. 1750-1760
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Tidskriftsartikel (refereegranskat)abstract
- Background. The herpes zoster subunit vaccine (HZ/su), consisting of varicella-zoster virus glycoprotein E (gE) and AS01(B) Adjuvant System, was highly efficacious in preventing herpes zoster in the ZOE-50 and ZOE-70 trials. We present immunogenicity results from those trials. Methods. Participants (ZOE-50: >= 50; ZOE-70: >= 70 years of age) received 2 doses of HZ/su or placebo, 2 months apart. Serum anti-gE antibodies and CD4 T cells expressing >= 2 of 4 activation markers assessed (CD4(2+)) after stimulation with gE-peptides were measured in subcohorts for humoral (n = 3293) and cell-mediated (n = 466) immunogenicity. Results. After vaccination, 97.8% of HZ/su and 2.0% of placebo recipients showed a humoral response. Geometric mean anti-gE antibody concentrations increased 39.1-fold and 8.3-fold over baseline in HZ/su recipients at 1 and 36 months post-dose 2, respectively. A gE-specific CD4(2+) T-cell response was shown in 93.3% of HZ/su and 0% of placebo recipients. Median CD42+ T-cell frequencies increased 24.6-fold (1 month) and 7.9-fold (36 months) over baseline in HZ/su recipients and remained >= 5.6-fold above baseline in all age groups at 36 months. The proportion of CD4 T cells expressing all 4 activation markers increased over time in all age groups. Conclusions. Most HZ/su recipients developed robust immune responses persisting for 3 years following vaccination.
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| 47. |
- Dick, Jan, et al.
(författare)
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Testing the ecosystem service cascade framework and QUICKScan software tool in the context of land use planning in Glenlivet Estate Scotland
- 2017
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Ingår i: International Journal of Biodiversity Science, Ecosystem Services & Management. - : Taylor & Francis. - 2151-3732 .- 2151-3740. ; 13:2, s. 12-25
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Tidskriftsartikel (refereegranskat)abstract
- The concept of ecosystem services has been extensively studied in recent decades. Most studies have focused on describing the specific aspects such as production, spatial extent, valuation of services and the trade-off between services. Few studies however assess the practitioners? views on the frameworks, models or tools developed. In this paper, we report on a multi-stakeholder workshop where two tools were tested (i) the ecosystem service cascade framework was tested as a means to frame the issues and (ii) a participatory-spatial modelling method, QUICKScan, was tested as an aid to support discussion over natural resource management and planning in a multi-use landscape. A focused group discussion was utilised to determine stakeholders? views of the cascade framework and pre- and post-workshop questionnaires quantified the stakeholders? views of the QUICKScan method. The stakeholders identified both positive and negative aspects of both tools. The diversity of views expressed were associated with (i) the past experience of the individual with the issues discussed, (ii) the technical aspects of the tools i.e. the ability with GIS and (iii) the level of new shared knowledge they reported acquiring on the day which was related to their initial knowledge of the issue and area studied.
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| 48. |
- Enver, Tariq, et al.
(författare)
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Stem Cell States, Fates, and the Rules of Attraction
- 2009
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Ingår i: Cell Stem Cell. - : Elsevier BV. - 1934-5909. ; 4:5, s. 387-397
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Forskningsöversikt (refereegranskat)abstract
- Understanding cell-fate decisions in stem cell populations is a major goal of modern biology. Stem and progenitor cell populations are often heterogeneous, which may reflect stem cell subsets that express subtly different properties, including different propensities for lineage selection upon differentiation, yet remain able to interconvert. We discuss these properties with examples both from the hematopoietic and embryonic stem cell (ESC) systems. The nature of the stem cell substates and their relationship to commitment to differentiate and lineage selection can be elucidated in terms of a landscape picture in which stable states can be defined mathematically as attractors.
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| 49. |
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| 50. |
- Galluzzi, L, et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring cell death in higher eukaryotes.
- 2009
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Ingår i: Cell death and differentiation. - : Springer Science and Business Media LLC. - 1476-5403 .- 1350-9047. ; 16:8, s. 1093-107
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Forskningsöversikt (refereegranskat)abstract
- Cell death is essential for a plethora of physiological processes, and its deregulation characterizes numerous human diseases. Thus, the in-depth investigation of cell death and its mechanisms constitutes a formidable challenge for fundamental and applied biomedical research, and has tremendous implications for the development of novel therapeutic strategies. It is, therefore, of utmost importance to standardize the experimental procedures that identify dying and dead cells in cell cultures and/or in tissues, from model organisms and/or humans, in healthy and/or pathological scenarios. Thus far, dozens of methods have been proposed to quantify cell death-related parameters. However, no guidelines exist regarding their use and interpretation, and nobody has thoroughly annotated the experimental settings for which each of these techniques is most appropriate. Here, we provide a nonexhaustive comparison of methods to detect cell death with apoptotic or nonapoptotic morphologies, their advantages and pitfalls. These guidelines are intended for investigators who study cell death, as well as for reviewers who need to constructively critique scientific reports that deal with cellular demise. Given the difficulties in determining the exact number of cells that have passed the point-of-no-return of the signaling cascades leading to cell death, we emphasize the importance of performing multiple, methodologically unrelated assays to quantify dying and dead cells.
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