| 1. |
- Niemi, MEK, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 2. |
- Fenstermacher, M.E., et al.
(författare)
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DIII-D research advancing the physics basis for optimizing the tokamak approach to fusion energy
- 2022
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Ingår i: Nuclear Fusion. - : IOP Publishing. - 0029-5515 .- 1741-4326. ; 62:4
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Tidskriftsartikel (refereegranskat)abstract
- DIII-D physics research addresses critical challenges for the operation of ITER and the next generation of fusion energy devices. This is done through a focus on innovations to provide solutions for high performance long pulse operation, coupled with fundamental plasma physics understanding and model validation, to drive scenario development by integrating high performance core and boundary plasmas. Substantial increases in off-axis current drive efficiency from an innovative top launch system for EC power, and in pressure broadening for Alfven eigenmode control from a co-/counter-I p steerable off-axis neutral beam, all improve the prospects for optimization of future long pulse/steady state high performance tokamak operation. Fundamental studies into the modes that drive the evolution of the pedestal pressure profile and electron vs ion heat flux validate predictive models of pedestal recovery after ELMs. Understanding the physics mechanisms of ELM control and density pumpout by 3D magnetic perturbation fields leads to confident predictions for ITER and future devices. Validated modeling of high-Z shattered pellet injection for disruption mitigation, runaway electron dissipation, and techniques for disruption prediction and avoidance including machine learning, give confidence in handling disruptivity for future devices. For the non-nuclear phase of ITER, two actuators are identified to lower the L-H threshold power in hydrogen plasmas. With this physics understanding and suite of capabilities, a high poloidal beta optimized-core scenario with an internal transport barrier that projects nearly to Q = 10 in ITER at ∼8 MA was coupled to a detached divertor, and a near super H-mode optimized-pedestal scenario with co-I p beam injection was coupled to a radiative divertor. The hybrid core scenario was achieved directly, without the need for anomalous current diffusion, using off-axis current drive actuators. Also, a controller to assess proximity to stability limits and regulate β N in the ITER baseline scenario, based on plasma response to probing 3D fields, was demonstrated. Finally, innovative tokamak operation using a negative triangularity shape showed many attractive features for future pilot plant operation.
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| 3. |
- Acharya, B. S., et al.
(författare)
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Introducing the CTA concept
- 2013
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Ingår i: Astroparticle physics. - : Elsevier BV. - 0927-6505 .- 1873-2852. ; 43, s. 3-18
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- The Cherenkov Telescope Array (CTA) is a new observatory for very high-energy (VHE) gamma rays. CTA has ambitions science goals, for which it is necessary to achieve full-sky coverage, to improve the sensitivity by about an order of magnitude, to span about four decades of energy, from a few tens of GeV to above 100 TeV with enhanced angular and energy resolutions over existing VHE gamma-ray observatories. An international collaboration has formed with more than 1000 members from 27 countries in Europe, Asia, Africa and North and South America. In 2010 the CTA Consortium completed a Design Study and started a three-year Preparatory Phase which leads to production readiness of CTA in 2014. In this paper we introduce the science goals and the concept of CTA, and provide an overview of the project. (C) 2013 Elsevier B.V. All rights reserved.
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| 4. |
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| 5. |
- Actis, M., et al.
(författare)
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Design concepts for the Cherenkov Telescope Array CTA : an advanced facility for ground-based high-energy gamma-ray astronomy
- 2011
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Ingår i: Experimental astronomy. - : Springer. - 0922-6435 .- 1572-9508. ; 32:3, s. 193-316
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Tidskriftsartikel (refereegranskat)abstract
- Ground-based gamma-ray astronomy has had a major breakthrough with the impressive results obtained using systems of imaging atmospheric Cherenkov telescopes. Ground-based gamma-ray astronomy has a huge potential in astrophysics, particle physics and cosmology. CTA is an international initiative to build the next generation instrument, with a factor of 5-10 improvement in sensitivity in the 100 GeV-10 TeV range and the extension to energies well below 100 GeV and above 100 TeV. CTA will consist of two arrays (one in the north, one in the south) for full sky coverage and will be operated as open observatory. The design of CTA is based on currently available technology. This document reports on the status and presents the major design concepts of CTA.
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| 6. |
- Zuntini, Alexandre R., et al.
(författare)
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Phylogenomics and the rise of the angiosperms
- 2024
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Ingår i: NATURE. - 0028-0836 .- 1476-4687. ; 629, s. 843-850
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Tidskriftsartikel (refereegranskat)abstract
- Angiosperms are the cornerstone of most terrestrial ecosystems and human livelihoods(1,2). A robust understanding of angiosperm evolution is required to explain their rise to ecological dominance. So far, the angiosperm tree of life has been determined primarily by means of analyses of the plastid genome(3,4). Many studies have drawn on this foundational work, such as classification and first insights into angiosperm diversification since their Mesozoic origins(5-7). However, the limited and biased sampling of both taxa and genomes undermines confidence in the tree and its implications. Here, we build the tree of life for almost 8,000 (about 60%) angiosperm genera using a standardized set of 353 nuclear genes(8). This 15-fold increase in genus-level sampling relative to comparable nuclear studies(9) provides a critical test of earlier results and brings notable change to key groups, especially in rosids, while substantiating many previously predicted relationships. Scaling this tree to time using 200 fossils, we discovered that early angiosperm evolution was characterized by high gene tree conflict and explosive diversification, giving rise to more than 80% of extant angiosperm orders. Steady diversification ensued through the remaining Mesozoic Era until rates resurged in the Cenozoic Era, concurrent with decreasing global temperatures and tightly linked with gene tree conflict. Taken together, our extensive sampling combined with advanced phylogenomic methods shows the deep history and full complexity in the evolution of a megadiverse clade.
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| 7. |
- Acharyya, A., et al.
(författare)
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Monte Carlo studies for the optimisation of the Cherenkov Telescope Array layout
- 2019
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Ingår i: Astroparticle physics. - : Elsevier. - 0927-6505 .- 1873-2852. ; 111, s. 35-53
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Tidskriftsartikel (refereegranskat)abstract
- The Cherenkov Telescope Array (CTA) is the major next-generation observatory for ground-based veryhigh-energy gamma-ray astronomy. It will improve the sensitivity of current ground-based instruments by a factor of five to twenty, depending on the energy, greatly improving both their angular and energy resolutions over four decades in energy (from 20 GeV to 300 TeV). This achievement will be possible by using tens of imaging Cherenkov telescopes of three successive sizes. They will be arranged into two arrays, one per hemisphere, located on the La Palma island (Spain) and in Paranal (Chile). We present here the optimised and final telescope arrays for both CTA sites, as well as their foreseen performance, resulting from the analysis of three different large-scale Monte Carlo productions.
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| 8. |
- 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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| 9. |
- Ahmadi, M., et al.
(författare)
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Characterization of the 1S-2S transition in antihydrogen
- 2018
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 557:7703, s. 71-
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Tidskriftsartikel (refereegranskat)abstract
- In 1928, Dirac published an equation(1) that combined quantum mechanics and special relativity. Negative-energy solutions to this equation, rather than being unphysical as initially thought, represented a class of hitherto unobserved and unimagined particles-antimatter. The existence of particles of antimatter was confirmed with the discovery of the positron(2) (or anti-electron) by Anderson in 1932, but it is still unknown why matter, rather than antimatter, survived after the Big Bang. As a result, experimental studies of antimatter(3-7), including tests of fundamental symmetries such as charge-parity and charge-parity-time, and searches for evidence of primordial antimatter, such as antihelium nuclei, have high priority in contemporary physics research. The fundamental role of the hydrogen atom in the evolution of the Universe and in the historical development of our understanding of quantum physics makes its antimatter counterpart-the antihydrogen atom-of particular interest. Current standard-model physics requires that hydrogen and antihydrogen have the same energy levels and spectral lines. The laser-driven 1S-2S transition was recently observed(8) in antihydrogen. Here we characterize one of the hyperfine components of this transition using magnetically trapped atoms of antihydrogen and compare it to model calculations for hydrogen in our apparatus. We find that the shape of the spectral line agrees very well with that expected for hydrogen and that the resonance frequency agrees with that in hydrogen to about 5 kilohertz out of 2.5 x 10(15) hertz. This is consistent with charge-parity-time invariance at a relative precision of 2 x 10(-12)-two orders of magnitude more precise than the previous determination(8)-corresponding to an absolute energy sensitivity of 2 x 10(-20) GeV.
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| 10. |
- Ahmadi, M., et al.
(författare)
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Investigation of the fine structure of antihydrogen
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 578:7795, s. 375-380
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Tidskriftsartikel (refereegranskat)abstract
- At the historic Shelter Island Conference on the Foundations of Quantum Mechanics in 1947, Willis Lamb reported an unexpected feature in the fine structure of atomic hydrogen: a separation of the 2S(1/2) and 2P(1/2) states(1). The observation of this separation, now known as the Lamb shift, marked an important event in the evolution of modern physics, inspiring others to develop the theory of quantum electrodynamics(2-5). Quantum electrodynamics also describes antimatter, but it has only recently become possible to synthesize and trap atomic antimatter to probe its structure. Mirroring the historical development of quantum atomic physics in the twentieth century, modern measurements on anti-atoms represent a unique approach for testing quantum electrodynamics and the foundational symmetries of the standard model. Here we report measurements of the fine structure in the n = 2 states of antihydrogen, the antimatter counterpart of the hydrogen atom. Using optical excitation of the 1S-2P Lyman-alpha transitions in antihydrogen(6), we determine their frequencies in a magnetic field of 1 tesla to a precision of 16 parts per billion. Assuming the standard Zeeman and hyperfine interactions, we infer the zero-field fine-structure splitting (2P(1/2)-2P(3/2)) in antihydrogen. The resulting value is consistent with the predictions of quantum electrodynamics to a precision of 2 per cent. Using our previously measured value of the 1S-2S transition frequency(6,7), we find that the classic Lamb shift in antihydrogen (2S(1/2)-2P(1/2) splitting at zero field) is consistent with theory at a level of 11 per cent. Our observations represent an important step towards precision measurements of the fine structure and the Lamb shift in the antihydrogen spectrum as tests of the charge-parity-time symmetry(8) and towards the determination of other fundamental quantities, such as the antiproton charge radius(9,10), in this antimatter system. Precision measurements of the 1S-2P transition in antihydrogen that take into account the standard Zeeman and hyperfine effects confirm the predictions of quantum electrodynamics.
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| 11. |
- Ahmadi, M., et al.
(författare)
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Observation of the 1S-2P Lyman-alpha transition in antihydrogen
- 2018
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 561:7722, s. 211-217
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Tidskriftsartikel (refereegranskat)abstract
- In 1906, Theodore Lyman discovered his eponymous series of transitions in the extreme-ultraviolet region of the atomic hydrogen spectrum(1,2). The patterns in the hydrogen spectrum helped to establish the emerging theory of quantum mechanics, which we now know governs the world at the atomic scale. Since then, studies involving the Lyman-alpha line-the 1S-2P transition at a wavelength of 121.6 nanometres-have played an important part in physics and astronomy, as one of the most fundamental atomic transitions in the Universe. For example, this transition has long been used by astronomers studying the intergalactic medium and testing cosmological models via the so-called 'Lyman-alpha forest('3) of absorption lines at different redshifts. Here we report the observation of the Lyman-alpha transition in the antihydrogen atom, the antimatter counterpart of hydrogen. Using narrow-line-width, nanosecond-pulsed laser radiation, the 1S-2P transition was excited in magnetically trapped antihydrogen. The transition frequency at a field of 1.033 tesla was determined to be 2,466,051.7 +/- 0.12 gigahertz (1 sigma uncertainty) and agrees with the prediction for hydrogen to a precision of 5 x 10(-8). Comparisons of the properties of antihydrogen with those of its well-studied matter equivalent allow precision tests of fundamental symmetries between matter ;and antimatter. Alongside the ground-state hyperfine(4,5) and 1S-2S transitions(6,7) recently observed in antihydrogen, the Lyman-alpha transition will permit laser cooling of antihydrogen(8,9), thus providing a cold and dense sample of anti-atoms for precision spectroscopy and gravity measurements(10). In addition to the observation of this fundamental transition, this work represents both a decisive technological step towards laser cooling of antihydrogen, and the extension of antimatter spectroscopy to quantum states possessing orbital angular momentum.
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| 12. |
- Alffenaar, J. W. C., et al.
(författare)
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Clinical standards for the dosing and management of TB drugs
- 2022
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Ingår i: The International Journal of Tuberculosis and Lung Disease. - Paris, France : International Union Against Tuberculosis and Lung Disease. - 1027-3719 .- 1815-7920. ; 26:6, s. 483-
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Optimal drug dosing is important to ensure adequate response to treatment, prevent development of drug resistance and reduce drug toxicity. The aim of these clinical standards is to provide guidance on 'best practice' for dosing and management of TB drugs.Methods: A panel of 57 global experts in the fields of microbiology, pharmacology and TB care were identified; 51 participated in a Delphi process. A 5-point Likert scale was used to score draft standards. The final document represents the broad consensus and was approved by all participants.Results: Six clinical standards were defined: Standard 1, defining the most appropriate initial dose for TB treatment; Standard 2, identifying patients who may be at risk of sub-optimal drug exposure; Standard 3, identifying patients at risk of developing drug-related toxicity and how best to manage this risk; Standard 4, identifying patients who can benefit from therapeutic drug monitoring (TDM); Standard 5, highlighting education and counselling that should be provided to people initiating TB treatment; and Standard 6, providing essential education for healthcare professionals. In addition, consensus research priorities were identified.Conclusion: This is the first consensus-based Clinical Standards for the dosing and management of TB drugs to guide clinicians and programme managers in planning and implementation of locally appropriate measures for optimal person-centred treatment to improve patient care.
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| 13. |
- Baker, C. J., et al.
(författare)
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Laser cooling of antihydrogen atoms
- 2021
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 592:7852, s. 35-42
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Tidskriftsartikel (refereegranskat)abstract
- The photon-the quantum excitation of the electromagnetic field-is massless but carries momentum. A photon can therefore exert a force on an object upon collision(1). Slowing the translational motion of atoms and ions by application of such a force(2,3), known as laser cooling, was first demonstrated 40 years ago(4,5). It revolutionized atomic physics over the following decades(6-8), and it is now a workhorse in many fields, including studies on quantum degenerate gases, quantum information, atomic clocks and tests of fundamental physics. However, this technique has not yet been applied to antimatter. Here we demonstrate laser cooling of antihydrogen(9), the antimatter atom consisting of an antiproton and a positron. By exciting the 1S-2P transition in antihydrogen with pulsed, narrow-linewidth, Lyman-alpha laser radiation(10,11), we Doppler-cool a sample of magnetically trapped antihydrogen. Although we apply laser cooling in only one dimension, the trap couples the longitudinal and transverse motions of the anti-atoms, leading to cooling in all three dimensions. We observe a reduction in the median transverse energy by more than an order of magnitude-with a substantial fraction of the anti-atoms attaining submicroelectronvolt transverse kinetic energies. We also report the observation of the laser-driven 1S-2S transition in samples of laser-cooled antihydrogen atoms. The observed spectral line is approximately four times narrower than that obtained without laser cooling. The demonstration of laser cooling and its immediate application has far-reaching implications for antimatter studies. A more localized, denser and colder sample of antihydrogen will drastically improve spectroscopic(11-13) and gravitational(14) studies of antihydrogen in ongoing experiments. Furthermore, the demonstrated ability to manipulate the motion of antimatter atoms by laser light will potentially provide ground-breaking opportunities for future experiments, such as anti-atomic fountains, anti-atom interferometry and the creation of antimatter molecules.
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| 14. |
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| 15. |
- Singh, K. P., et al.
(författare)
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Clinical standards for the management of adverse effects during treatment for TB
- 2023
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Ingår i: The International Journal of Tuberculosis and Lung Disease. - : International Union Against Tuberculosis and Lung Disease. - 1027-3719 .- 1815-7920. ; 27:7, s. 506-519
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Adverse effects (AE) to TB treatment cause morbidity, mortality and treatment interruption. The aim of these clinical standards is to encourage best practise for the diagnosis and management of AE.METHODS: 65/81 invited experts participated in a Delphi process using a 5-point Likert scale to score draft standards.RESULTS: We identified eight clinical standards. Each person commencing treatment for TB should: Standard 1, be counselled regarding AE before and during treatment; Standard 2, be evaluated for factors that might increase AE risk with regular review to actively identify and manage these; Standard 3, when AE occur, carefully assessed and possible allergic or hypersensitiv-ity reactions considered; Standard 4, receive appropriate care to minimise morbidity and mortality associated with AE; Standard 5, be restarted on TB drugs after a serious AE according to a standardised protocol that includes active drug safety monitoring. In addition: Standard 6, healthcare workers should be trained on AE including how to counsel people undertaking TB treatment, as well as active AE monitoring and management; Standard 7, there should be active AE monitoring and reporting for all new TB drugs and regimens; and Standard 8, knowledge gaps identified from active AE monitoring should be systematically addressed through clinical research.CONCLUSION: These standards provide a person -centred, consensus-based approach to minimise the impact of AE TB treatment.
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| 16. |
- 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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| 17. |
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| 18. |
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| 19. |
- Schoch, CL, et al.
(författare)
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Nuclear ribosomal internal transcribed spacer (ITS) region as a universal DNA barcode marker for Fungi
- 2012
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490. ; 109:16, s. 6241-6246
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Tidskriftsartikel (refereegranskat)abstract
- Six DNA regions were evaluated as potential DNA barcodes for Fungi, the second largest kingdom of eukaryotic life, by a multinational, multilaboratory consortium. The region of the mitochondrial cytochrome c oxidase subunit 1 used as the animal barcode was excluded as a potential marker, because it is difficult to amplify in fungi, often includes large introns, and can be insufficiently variable. Three subunits from the nuclear ribosomal RNA cistron were compared together with regions of three representative protein-coding genes (largest subunit of RNA polymerase II, second largest subunit of RNA polymerase II, and minichromosome maintenance protein). Although the protein-coding gene regions often had a higher percent of correct identification compared with ribosomal markers, low PCR amplification and sequencing success eliminated them as candidates for a universal fungal barcode. Among the regions of the ribosomal cistron, the internal transcribed spacer (ITS) region has the highest probability of successful identification for the broadest range of fungi, with the most clearly defined barcode gap between inter- and intraspecific variation. The nuclear ribosomal large subunit, a popular phylogenetic marker in certain groups, had superior species resolution in some taxonomic groups, such as the early diverging lineages and the ascomycete yeasts, but was otherwise slightly inferior to the ITS. The nuclear ribosomal small subunit has poor species-level resolution in fungi. ITS will be formally proposed for adoption as the primary fungal barcode marker to the Consortium for the Barcode of Life, with the possibility that supplementary barcodes may be developed for particular narrowly circumscribed taxonomic groups.
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| 20. |
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| 21. |
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| 22. |
- Arrowsmith, CH, et al.
(författare)
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The promise and peril of chemical probes
- 2015
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Ingår i: Nature chemical biology. - : Springer Science and Business Media LLC. - 1552-4469 .- 1552-4450. ; 11:8, s. 536-541
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Tidskriftsartikel (refereegranskat)
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| 23. |
- Gehlen, J., et al.
(författare)
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First genome-wide association study of esophageal atresia identifies three genetic risk loci at CTNNA3, FOXF1/FOXC2/FOXL1, and HNF1B
- 2022
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Ingår i: Human Genetics and Genomics Advances. - : Elsevier BV. - 2666-2477. ; 3:2
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Tidskriftsartikel (refereegranskat)abstract
- Esophageal atresia with or without tracheoesophageal fistula (EA/TEF) is the most common congenital malformation of the upper digestive tract. This study represents the first genome-wide association study (GWAS) to identify risk loci for EA/TEF. We used a European case-control sample comprising 764 EA/TEF patients and 5,778 controls and observed genome-wide significant associations at three loci. On chromosome 10q21 within the gene CTNNA3 (p = 2.11 × 10−8; odds ratio [OR] = 3.94; 95% confidence interval [CI], 3.10–5.00), on chromosome 16q24 next to the FOX gene cluster (p = 2.25 × 10−10; OR = 1.47; 95% CI, 1.38–1.55) and on chromosome 17q12 next to the gene HNF1B (p = 3.35 × 10−16; OR = 1.75; 95% CI, 1.64–1.87). We next carried out an esophageal/tracheal transcriptome profiling in rat embryos at four selected embryonic time points. Based on these data and on already published data, the implicated genes at all three GWAS loci are promising candidates for EA/TEF development. We also analyzed the genetic EA/TEF architecture beyond the single marker level, which revealed an estimated single-nucleotide polymorphism (SNP)-based heritability of around 37% ± 14% standard deviation. In addition, we examined the polygenicity of EA/TEF and found that EA/TEF is less polygenic than other complex genetic diseases. In conclusion, the results of our study contribute to a better understanding on the underlying genetic architecture of ET/TEF with the identification of three risk loci and candidate genes. © 2022 The Authors
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| 24. |
- Mingardo, E, et al.
(författare)
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A genome-wide association study with tissue transcriptomics identifies genetic drivers for classic bladder exstrophy
- 2022
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Ingår i: Communications biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 5:1, s. 1203-
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Tidskriftsartikel (refereegranskat)abstract
- Classic bladder exstrophy represents the most severe end of all human congenital anomalies of the kidney and urinary tract and is associated with bladder cancer susceptibility. Previous genetic studies identified one locus to be involved in classic bladder exstrophy, but were limited to a restrict number of cohort. Here we show the largest classic bladder exstrophy genome-wide association analysis to date where we identify eight genome-wide significant loci, seven of which are novel. In these regions reside ten coding and four non-coding genes. Among the coding genes is EFNA1, strongly expressed in mouse embryonic genital tubercle, urethra, and primitive bladder. Re-sequence of EFNA1 in the investigated classic bladder exstrophy cohort of our study displays an enrichment of rare protein altering variants. We show that all coding genes are expressed and/or significantly regulated in both mouse and human embryonic developmental bladder stages. Furthermore, nine of the coding genes residing in the regions of genome-wide significance are differentially expressed in bladder cancers. Our data suggest genetic drivers for classic bladder exstrophy, as well as a possible role for these drivers to relevant bladder cancer susceptibility.
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| 25. |
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