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Sökning: WFRF:(O’Rourke Michael)

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2.
  • Raghavan, Maanasa, et al. (författare)
  • The genetic prehistory of the New World Arctic
  • 2014
  • Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 345:6200, s. 1020-
  • Tidskriftsartikel (refereegranskat)abstract
    • The New World Arctic, the last region of the Americas to be populated by humans, has a relatively well-researched archaeology, but an understanding of its genetic history is lacking. We present genome-wide sequence data from ancient and present-day humans from Greenland, Arctic Canada, Alaska, Aleutian Islands, and Siberia. We show that Paleo-Eskimos (similar to 3000 BCE to 1300 CE) represent a migration pulse into the Americas independent of both Native American and Inuit expansions. Furthermore, the genetic continuity characterizing the Paleo-Eskimo period was interrupted by the arrival of a new population, representing the ancestors of present-day Inuit, with evidence of past gene flow between these lineages. Despite periodic abandonment of major Arctic regions, a single Paleo-Eskimo metapopulation likely survived in near-isolation for more than 4000 years, only to vanish around 700 years ago.
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3.
  • Binder, Zev A., et al. (författare)
  • Epidermal Growth Factor Receptor Extracellular Domain Mutations in Glioblastoma Present Opportunities for Clinical Imaging and Therapeutic Development
  • 2018
  • Ingår i: Cancer Cell. - : Elsevier BV. - 1535-6108 .- 1878-3686. ; 34:1, s. 163-177
  • Tidskriftsartikel (refereegranskat)abstract
    • We explored the clinical and pathological impact of epidermal growth factor receptor (EGFR) extracellular domain missense mutations. Retrospective assessment of 260 de novo glioblastoma patients revealed a significant reduction in overall survival of patients having tumors with EGFR mutations at alanine 289 (EGFR(A289D/T/V)). Quantitative multi-parametric magnetic resonance imaging analyses indicated increased tumor invasion for EGFR(A289D/T/V) mutants, corroborated in mice bearing intracranial tumors expressing EGFR(A289V) and dependent on ERK-mediated expression of matrix metalloproteinase-1. EGFR(A289V) tumor growth was attenuated with an antibody against a cryptic epitope, based on in silico simulation. The findings of this study indicate a highly invasive phenotype associated with the EGFR(A289V) mutation in glioblastoma, postulating EGFR(A289V) as a molecular marker for responsiveness to therapy with EGFR-targeting antibodies.
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5.
  • Gillmann, Cedric, et al. (författare)
  • The Long-Term Evolution of the Atmosphere of Venus : Processes and Feedback Mechanisms Interior-Exterior Exchanges
  • 2022
  • Ingår i: Space Science Reviews. - : Springer. - 0038-6308 .- 1572-9672. ; 218:7
  • Forskningsöversikt (refereegranskat)abstract
    • This work reviews the long-term evolution of the atmosphere of Venus, and modulation of its composition by interior/exterior cycling. The formation and evolution of Venus's atmosphere, leading to contemporary surface conditions, remain hotly debated topics, and involve questions that tie into many disciplines. We explore these various inter-related mechanisms which shaped the evolution of the atmosphere, starting with the volatile sources and sinks. Going from the deep interior to the top of the atmosphere, we describe volcanic outgassing, surface-atmosphere interactions, and atmosphere escape. Furthermore, we address more complex aspects of the history of Venus, including the role of Late Accretion impacts, how magnetic field generation is tied into long-term evolution, and the implications of geochemical and geodynamical feedback cycles for atmospheric evolution. We highlight plausible end-member evolutionary pathways that Venus could have followed, from accretion to its present-day state, based on modeling and observations. In a first scenario, the planet was desiccated by atmospheric escape during the magma ocean phase. In a second scenario, Venus could have harbored surface liquid water for long periods of time, until its temperate climate was destabilized and it entered a runaway greenhouse phase. In a third scenario, Venus's inefficient outgassing could have kept water inside the planet, where hydrogen was trapped in the core and the mantle was oxidized. We discuss existing evidence and future observations/missions required to refine our understanding of the planet's history and of the complex feedback cycles between the interior, surface, and atmosphere that have been operating in the past, present or future of Venus.
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6.
  • Malhotra, Rajeev, et al. (författare)
  • HDAC9 is implicated in atherosclerotic aortic calcification and affects vascular smooth muscle cell phenotype
  • 2019
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 51:11, s. 1580-
  • Tidskriftsartikel (refereegranskat)abstract
    • Aortic calcification is an important independent predictor of future cardiovascular events. We performed a genome-wide association meta-analysis to determine SNPs associated with the extent of abdominal aortic calcification (n = 9,417) or descending thoracic aortic calcification (n = 8,422). Two genetic loci, HDAC9 and RAP1GAP, were associated with abdominal aortic calcification at a genome-wide level (P < 5.0 × 10−8). No SNPs were associated with thoracic aortic calcification at the genome-wide threshold. Increased expression of HDAC9 in human aortic smooth muscle cells promoted calcification and reduced contractility, while inhibition of HDAC9 in human aortic smooth muscle cells inhibited calcification and enhanced cell contractility. In matrix Gla protein–deficient mice, a model of human vascular calcification, mice lacking HDAC9 had a 40% reduction in aortic calcification and improved survival. This translational genomic study identifies the first genetic risk locus associated with calcification of the abdominal aorta and describes a previously unknown role for HDAC9 in the development of vascular calcification.
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7.
  • O'Rourke, Joseph G., et al. (författare)
  • Venus, the Planet : Introduction to the Evolution of Earth's Sister Planet
  • 2023
  • Ingår i: Space Science Reviews. - : Springer. - 0038-6308 .- 1572-9672. ; 219:1
  • Forskningsöversikt (refereegranskat)abstract
    • Venus is the planet in the Solar System most similar to Earth in terms of size and (probably) bulk composition. Until the mid-20th century, scientists thought that Venus was a verdant world-inspiring science-fictional stories of heroes battling megafauna in sprawling jungles. At the start of the Space Age, people learned that Venus actually has a hellish surface, baked by the greenhouse effect under a thick, CO2-rich atmosphere. In popular culture, Venus was demoted from a jungly playground to (at best) a metaphor for the redemptive potential of extreme adversity. However, whether Venus was much different in the past than it is today remains unknown. In this review, we show how now-popular models for the evolution of Venus mirror how the scientific understanding of modern Venus has changed over time. Billions of years ago, Venus could have had a clement surface with water oceans. Venus perhaps then underwent at least one dramatic transition in atmospheric, surface, and interior conditions before present day. This review kicks off a topical collection about all aspects of Venus's evolution and how understanding Venus can teach us about other planets, including exoplanets. Here we provide the general background and motivation required to delve into the other manuscripts in this collection. Finally, we discuss how our ignorance about the evolution of Venus motivated the prioritization of new spacecraft missions that will rediscover Earth's nearest planetary neighbor-beginning a new age of Venus exploration.
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8.
  • Sloyan, Bernadette M., et al. (författare)
  • The global ocean ship-base hydrographic investigations program (GO-SHIP): A platform for integrated multidisciplinary ocean science
  • 2019
  • Ingår i: Frontiers in Marine Science. - : Frontiers Media SA. - 2296-7745. ; 6
  • Tidskriftsartikel (refereegranskat)abstract
    • The Global Ocean Ship-Based Hydrographic Investigations Program (GO-SHIP) provides a globally coordinated network and oversight of 55 sustained decadal repeat hydrographic reference (core) lines as part of the global ocean/climate observing systems (GOOS/GCOS) for study of physical oceanography, the ocean carbon, oxygen and nutrient cycles, and marine biogeochemistry. GO-SHIP enables assessment of the ocean sequestration of heat and carbon, changing ocean circulation and ventilation patterns, and their effects on ocean health and Earth's climate. Rapid quality control and open data release along with incorporation of the GO-SHIP effort in the Joint Technical Commission for Oceanography and Marine Meteorology (JCOMM) in situ Observing Programs Support Center (JCOMMOPS) have increased the profile of, and participation in, the program and led to increased data use for a range of efforts.
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9.
  • Way, Michael J., et al. (författare)
  • Synergies Between Venus & Exoplanetary Observations : Venus and Its Extrasolar Siblings
  • 2023
  • Ingår i: Space Science Reviews. - : Springer Nature. - 0038-6308 .- 1572-9672. ; 219:1
  • Forskningsöversikt (refereegranskat)abstract
    • Here we examine how our knowledge of present day Venus can inform terrestrial exoplanetary science and how exoplanetary science can inform our study of Venus. In a superficial way the contrasts in knowledge appear stark. We have been looking at Venus for millennia and studying it via telescopic observations for centuries. Spacecraft observations began with Mariner 2 in 1962 when we confirmed that Venus was a hothouse planet, rather than the tropical paradise science fiction pictured. As long as our level of exploration and understanding of Venus remains far below that of Mars, major questions will endure. On the other hand, exoplanetary science has grown leaps and bounds since the discovery of Pegasus 51b in 1995, not too long after the golden years of Venus spacecraft missions came to an end with the Magellan Mission in 1994. Multi-million to billion dollar/euro exoplanet focused spacecraft missions such as JWST, and its successors will be flown in the coming decades. At the same time, excitement about Venus exploration is blooming again with a number of confirmed and proposed missions in the coming decades from India, Russia, Japan, the European Space Agency (ESA) and the National Aeronautics and Space Administration (NASA). Here we review what is known and what we may discover tomorrow in complementary studies of Venus and its exoplanetary cousins.
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10.
  • Widemann, Thomas, et al. (författare)
  • Venus Evolution Through Time : Key Science Questions, Selected Mission Concepts and Future Investigations
  • 2023
  • Ingår i: Space Science Reviews. - : SPRINGER. - 0038-6308 .- 1572-9672. ; 219:7
  • Forskningsöversikt (refereegranskat)abstract
    • In this work we discuss various selected mission concepts addressing Venus evolution through time. More specifically, we address investigations and payload instrument concepts supporting scientific goals and open questions presented in the companion articles of this volume. Also included are their related investigations (observations & modeling) and discussion of which measurements and future data products are needed to better constrain Venus' atmosphere, climate, surface, interior and habitability evolution through time. A new fleet of Venus missions has been selected, and new mission concepts will continue to be considered for future selections. Missions under development include radar-equipped ESA-led EnVision M5 orbiter mission (European Space Agency 2021), NASA-JPL's VERITAS orbiter mission (Smrekar et al. 2022a), NASA-GSFC's DAVINCI entry probe/flyby mission (Garvin et al. 2022a). The data acquired with the VERITAS, DAVINCI, and EnVision from the end of this decade will fundamentally improve our understanding of the planet's long term history, current activity and evolutionary path. We further describe future mission concepts and measurements beyond the current framework of selected missions, as well as the synergies between these mission concepts, ground-based and space-based observatories and facilities, laboratory measurements, and future algorithmic or modeling activities that pave the way for the development of a Venus program that extends into the 2040s (Wilson et al. 2022).
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