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1.
  • Romanelli, F, et al. (author)
  • Overview of the JET results
  • 2011
  • In: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 51:9
  • Journal article (peer-reviewed)abstract
    • Since the last IAEA Conference JET has been in operation for one year with a programmatic focus on the qualification of ITER operating scenarios, the consolidation of ITER design choices and preparation for plasma operation with the ITER-like wall presently being installed in JET. Good progress has been achieved, including stationary ELMy H-mode operation at 4.5 MA. The high confinement hybrid scenario has been extended to high triangularity, lower ρ*and to pulse lengths comparable to the resistive time. The steady-state scenario has also been extended to lower ρ*and ν*and optimized to simultaneously achieve, under stationary conditions, ITER-like values of all other relevant normalized parameters. A dedicated helium campaign has allowed key aspects of plasma control and H-mode operation for the ITER non-activated phase to be evaluated. Effective sawtooth control by fast ions has been demonstrated with3He minority ICRH, a scenario with negligible minority current drive. Edge localized mode (ELM) control studies using external n = 1 and n = 2 perturbation fields have found a resonance effect in ELM frequency for specific q95values. Complete ELM suppression has, however, not been observed, even with an edge Chirikov parameter larger than 1. Pellet ELM pacing has been demonstrated and the minimum pellet size needed to trigger an ELM has been estimated. For both natural and mitigated ELMs a broadening of the divertor ELM-wetted area with increasing ELM size has been found. In disruption studies with massive gas injection up to 50% of the thermal energy could be radiated before, and 20% during, the thermal quench. Halo currents could be reduced by 60% and, using argon/deuterium and neon/deuterium gas mixtures, runaway electron generation could be avoided. Most objectives of the ITER-like ICRH antenna have been demonstrated; matching with closely packed straps, ELM resilience, scattering matrix arc detection and operation at high power density (6.2 MW m-2) and antenna strap voltages (42 kV). Coupling measurements are in very good agreement with TOPICA modelling. © 2011 IAEA, Vienna.
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2.
  • Abel, I, et al. (author)
  • Overview of the JET results with the ITER-like wall
  • 2013
  • In: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 53:10, s. 104002-
  • Journal article (peer-reviewed)abstract
    • Following the completion in May 2011 of the shutdown for the installation of the beryllium wall and the tungsten divertor, the first set of JET campaigns have addressed the investigation of the retention properties and the development of operational scenarios with the new plasma-facing materials. The large reduction in the carbon content (more than a factor ten) led to a much lower Z(eff) (1.2-1.4) during L- and H-mode plasmas, and radiation during the burn-through phase of the plasma initiation with the consequence that breakdown failures are almost absent. Gas balance experiments have shown that the fuel retention rate with the new wall is substantially reduced with respect to the C wall. The re-establishment of the baseline H-mode and hybrid scenarios compatible with the new wall has required an optimization of the control of metallic impurity sources and heat loads. Stable type-I ELMy H-mode regimes with H-98,H-y2 close to 1 and beta(N) similar to 1.6 have been achieved using gas injection. ELM frequency is a key factor for the control of the metallic impurity accumulation. Pedestal temperatures tend to be lower with the new wall, leading to reduced confinement, but nitrogen seeding restores high pedestal temperatures and confinement. Compared with the carbon wall, major disruptions with the new wall show a lower radiated power and a slower current quench. The higher heat loads on Be wall plasma-facing components due to lower radiation made the routine use of massive gas injection for disruption mitigation essential.
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3.
  • Elsik, Christine G., et al. (author)
  • The Genome Sequence of Taurine Cattle : A Window to Ruminant Biology and Evolution
  • 2009
  • In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 324:5926, s. 522-528
  • Journal article (peer-reviewed)abstract
    • To understand the biology and evolution of ruminants, the cattle genome was sequenced to about sevenfold coverage. The cattle genome contains a minimum of 22,000 genes, with a core set of 14,345 orthologs shared among seven mammalian species of which 1217 are absent or undetected in noneutherian (marsupial or monotreme) genomes. Cattle-specific evolutionary breakpoint regions in chromosomes have a higher density of segmental duplications, enrichment of repetitive elements, and species-specific variations in genes associated with lactation and immune responsiveness. Genes involved in metabolism are generally highly conserved, although five metabolic genes are deleted or extensively diverged from their human orthologs. The cattle genome sequence thus provides a resource for understanding mammalian evolution and accelerating livestock genetic improvement for milk and meat production.
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  • Carninci, P, et al. (author)
  • The transcriptional landscape of the mammalian genome
  • 2005
  • In: Science (New York, N.Y.). - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 309:5740, s. 1559-1563
  • Journal article (peer-reviewed)abstract
    • This study describes comprehensive polling of transcription start and termination sites and analysis of previously unidentified full-length complementary DNAs derived from the mouse genome. We identify the 5′ and 3′ boundaries of 181,047 transcripts with extensive variation in transcripts arising from alternative promoter usage, splicing, and polyadenylation. There are 16,247 new mouse protein-coding transcripts, including 5154 encoding previously unidentified proteins. Genomic mapping of the transcriptome reveals transcriptional forests, with overlapping transcription on both strands, separated by deserts in which few transcripts are observed. The data provide a comprehensive platform for the comparative analysis of mammalian transcriptional regulation in differentiation and development.
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5.
  • Forrest, ARR, et al. (author)
  • A promoter-level mammalian expression atlas
  • 2014
  • In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 507:7493, s. 462-
  • Journal article (peer-reviewed)
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6.
  • Sodergren, Erica, et al. (author)
  • The genome of the sea urchin Strongylocentrotus purpuratus.
  • 2006
  • In: Science. - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 314:5801, s. 941-52
  • Journal article (peer-reviewed)abstract
    • We report the sequence and analysis of the 814-megabase genome of the sea urchin Strongylocentrotus purpuratus, a model for developmental and systems biology. The sequencing strategy combined whole-genome shotgun and bacterial artificial chromosome (BAC) sequences. This use of BAC clones, aided by a pooling strategy, overcame difficulties associated with high heterozygosity of the genome. The genome encodes about 23,300 genes, including many previously thought to be vertebrate innovations or known only outside the deuterostomes. This echinoderm genome provides an evolutionary outgroup for the chordates and yields insights into the evolution of deuterostomes.
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7.
  • Noguchi, S, et al. (author)
  • FANTOM5 CAGE profiles of human and mouse samples
  • 2017
  • In: Scientific data. - : Springer Science and Business Media LLC. - 2052-4463. ; 4, s. 170112-
  • Journal article (peer-reviewed)abstract
    • In the FANTOM5 project, transcription initiation events across the human and mouse genomes were mapped at a single base-pair resolution and their frequencies were monitored by CAGE (Cap Analysis of Gene Expression) coupled with single-molecule sequencing. Approximately three thousands of samples, consisting of a variety of primary cells, tissues, cell lines, and time series samples during cell activation and development, were subjected to a uniform pipeline of CAGE data production. The analysis pipeline started by measuring RNA extracts to assess their quality, and continued to CAGE library production by using a robotic or a manual workflow, single molecule sequencing, and computational processing to generate frequencies of transcription initiation. Resulting data represents the consequence of transcriptional regulation in each analyzed state of mammalian cells. Non-overlapping peaks over the CAGE profiles, approximately 200,000 and 150,000 peaks for the human and mouse genomes, were identified and annotated to provide precise location of known promoters as well as novel ones, and to quantify their activities.
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  • Richards, Stephen, et al. (author)
  • Genome Sequence of the Pea Aphid Acyrthosiphon pisum
  • 2010
  • In: PLoS biology. - : Public Library of Science (PLoS). - 1544-9173 .- 1545-7885. ; 8:2, s. e1000313-
  • Journal article (peer-reviewed)abstract
    • Aphids are important agricultural pests and also biological models for studies of insect-plant interactions, symbiosis, virus vectoring, and the developmental causes of extreme phenotypic plasticity. Here we present the 464 Mb draft genome assembly of the pea aphid Acyrthosiphon pisum. This first published whole genome sequence of a basal hemimetabolous insect provides an outgroup to the multiple published genomes of holometabolous insects. Pea aphids are host-plant specialists, they can reproduce both sexually and asexually, and they have coevolved with an obligate bacterial symbiont. Here we highlight findings from whole genome analysis that may be related to these unusual biological features. These findings include discovery of extensive gene duplication in more than 2000 gene families as well as loss of evolutionarily conserved genes. Gene family expansions relative to other published genomes include genes involved in chromatin modification, miRNA synthesis, and sugar transport. Gene losses include genes central to the IMD immune pathway, selenoprotein utilization, purine salvage, and the entire urea cycle. The pea aphid genome reveals that only a limited number of genes have been acquired from bacteria; thus the reduced gene count of Buchnera does not reflect gene transfer to the host genome. The inventory of metabolic genes in the pea aphid genome suggests that there is extensive metabolite exchange between the aphid and Buchnera, including sharing of amino acid biosynthesis between the aphid and Buchnera. The pea aphid genome provides a foundation for post-genomic studies of fundamental biological questions and applied agricultural problems.
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  • Ericson, Per G P, 1956-, et al. (author)
  • A 14,000-year-old genome sheds light on the evolution and extinction of a Pleistocene vulture
  • 2022
  • In: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 5:1
  • Journal article (peer-reviewed)abstract
    • The New World Vulture [Coragyps] occidentalis (L. Miller, 1909) is one of many species that were extinct by the end of the Pleistocene. To understand its evolutionary history we sequenced the genome of a 14,000 year old [Coragyps] occidentalis found associated with megaherbivores in the Peruvian Andes. occidentalis has been viewed as the ancestor, or possibly sister, to the extant Black Vulture Coragyps atratus, but genomic data shows occidentalis to be deeply nested within the South American clade of atratus. Coragyps atratus inhabits lowlands, but the fossil record indicates that occidentalis mostly occupied high elevations. Our results suggest that occidentalis evolved from a population of atratus in southwestern South America that colonized the High Andes 300 to 400 kya. The morphological and morphometric differences between occidentalis and atratus may thus be explained by ecological diversification following from the natural selection imposed by this new and extreme, high elevation environment. The sudden evolution of a population with significantly larger body size and different anatomical proportions than atratus thus constitutes an example of punctuated evolution.
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18.
  • Jonsson, Per R., 1957, et al. (author)
  • Combining seascape connectivity with cumulative impact assessment in support of ecosystem-based marine spatial planning
  • 2021
  • In: Journal of Applied Ecology. - : Wiley. - 0021-8901 .- 1365-2664. ; 58:3
  • Journal article (peer-reviewed)abstract
    • Cumulative impact assessment (CIA) is a promising approach to guide marine spatial planning (MSP) and management. One limitation of CIA is the neglect of seascape connectivity, which may spread the impact of localized pressures to ambient areas, e.g. through lost dispersal and recruitment of organisms. We here, for the first time, incorporate seascape connectivity into a traditional CIA model using a connectivity matrix, exemplified by dispersal of propagules estimated through biophysical modelling. Two connectivity impacts are identified: the source impact represents downstream areas losing recruits because of reduced larval dispersal from sites affected by the pressure, and the sink impact represents loss of recruits originating from upstream areas prevented from settlement in the site affected by the local pressure. By including seascape connectivity in the Swedish MSP-guiding CIA tool Symphony we demonstrate how to practically account for remote effects of local environmental impact. Our example on blue mussel shows how reducing mussel fitness in a given area may have impacts on mussels far from the acting pressures. Overall, results indicate that connectivity impact for blue mussels plays a minor role in most areas, <10% of the ordinary cumulative impact. However, in some smaller areas, e.g. on offshore banks and the Danish Straits, seascape connectivity may increase ordinary cumulative impact with 20%-30%. In an example of scenario-based CIA analyses of MSP projections, we demonstrate how impacts of particular management actions, e.g. shipping rerouting and wind power developments, can be tracked far from the original area of influence. Depending on the dispersal ability of ecosystem components, a local pressure may impact a considerable area through seascape connectivity, transgressing management units and national borders. Although the mean connectivity impact may be modest for a single ecosystem component, the consideration of seascape connectivity across multiple ecosystem components may significantly alter the mapping of cumulative impact and the assessment of different MSP scenarios. Synthesis and applications. Our extension of Cumulative Impact Assessment offers a new method for mapping and practically integrating seascape connectivity with ecosystem-based MSP and other spatial instruments for policy making, such as marine protected areas.
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  • Monk, Bradley J., et al. (author)
  • A Randomized, Phase III Trial to Evaluate Rucaparib Monotherapy as Maintenance Treatment in Patients With Newly Diagnosed Ovarian Cancer (ATHENA-MONO/GOG-3020/ENGOT-ov45)
  • 2022
  • In: Journal of Clinical Oncology. - : Lippincott, Williams & Wilkins. - 0732-183X .- 1527-7755. ; 40:34, s. 3952-3964
  • Journal article (peer-reviewed)abstract
    • PURPOSEATHENA (ClinicalTrials.gov identifier: ) was designed to evaluate rucaparib first-line maintenance treatment in a broad patient population, including those without BRCA1 or BRCA2 (BRCA) mutations or other evidence of homologous recombination deficiency (HRD), or high-risk clinical characteristics such as residual disease. We report the results from the ATHENA-MONO comparison of rucaparib versus placebo.METHODSPatients with stage III-IV high-grade ovarian cancer undergoing surgical cytoreduction (R0/complete resection permitted) and responding to first-line platinum-doublet chemotherapy were randomly assigned 4:1 to oral rucaparib 600 mg twice a day or placebo. Stratification factors were HRD test status, residual disease after chemotherapy, and timing of surgery. The primary end point of investigator-assessed progression-free survival was assessed in a step-down procedure, first in the HRD population (BRCA-mutant or BRCA wild-type/loss of heterozygosity high tumor), and then in the intent-to-treat population.RESULTSAs of March 23, 2022 (data cutoff), 427 and 111 patients were randomly assigned to rucaparib or placebo, respectively (HRD population: 185 v 49). Median progression-free survival (95% CI) was 28.7 months (23.0 to not reached) with rucaparib versus 11.3 months (9.1 to 22.1) with placebo in the HRD population (log-rank P = .0004; hazard ratio [HR], 0.47; 95% CI, 0.31 to 0.72); 20.2 months (15.2 to 24.7) versus 9.2 months (8.3 to 12.2) in the intent-to-treat population (log-rank P < .0001; HR, 0.52; 95% CI, 0.40 to 0.68); and 12.1 months (11.1 to 17.7) versus 9.1 months (4.0 to 12.2) in the HRD-negative population (HR, 0.65; 95% CI, 0.45 to 0.95). The most common grade & GE; 3 treatment-emergent adverse events were anemia (rucaparib, 28.7% v placebo, 0%) and neutropenia (14.6% v 0.9%).CONCLUSIONRucaparib monotherapy is effective as first-line maintenance, conferring significant benefit versus placebo in patients with advanced ovarian cancer with and without HRD.
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  • Ravasi, Timothy, et al. (author)
  • An Atlas of Combinatorial Transcriptional Regulation in Mouse and Man
  • 2010
  • In: CELL. - : Elsevier BV. - 0092-8674 .- 1097-4172. ; 140:5, s. 744-752
  • Journal article (peer-reviewed)abstract
    • Combinatorial interactions among transcription factors are critical to directing tissue-specific gene expression. To build a global atlas of these combinations, we have screened for physical interactions among the majority of human and mouse DNA-binding transcription factors (TFs). The complete networks contain 762 human and 877 mouse interactions. Analysis of the networks reveals that highly connected TFs are broadly expressed across tissues, and that roughly half of the measured interactions are conserved between mouse and human. The data highlight the importance of TF combinations for determining cell fate, and they lead to the identification of a SMAD3/FLI1 complex expressed during development of immunity. The availability of large TF combinatorial networks in both human and mouse will provide many opportunities to study gene regulation, tissue differentiation, and mammalian evolution.
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  • Richards, Stephen, et al. (author)
  • The genome of the model beetle and pest Tribolium castaneum.
  • 2008
  • In: Nature. - 1476-4687. ; 452:7190, s. 949-55
  • Journal article (peer-reviewed)abstract
    • Tribolium castaneum is a representative of earth’s most numerous eukaryotic order, a powerful model organism for the study of generalized insect development, and also an important pest of stored agricultural products. We describe its genome sequence here. This omnivorous beetle has evolved an ability to interact with a diverse chemical environment as evidenced by large expansions in odorant and gustatory receptors, as well as p450 and other detoxification enzymes. Developmental patterns in Tribolium are more representative of other arthropods than those found in Drosophila, a fact represented in gene content and function. For one, Tribolium has retained more ancestral genes involved in cell-cell communication than Drosophila, and some are expressed in the growth zone crucial for axial elongation in short germ development. Systemic RNAi in T. castaneum appears to use mechanisms distinct from those found in C. elegans, but nevertheless offers similar power for the elucidation of gene function and identification of targets for selective insect control.
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  • Wahlstrom, I., et al. (author)
  • Projected climate change impact on a coastal sea-As significant as all current pressures combined
  • 2022
  • In: Global Change Biology. - : Wiley. - 1354-1013 .- 1365-2486. ; 28:17, s. 5310-5319
  • Journal article (peer-reviewed)abstract
    • Climate change influences the ocean's physical and biogeochemical conditions, causing additional pressures on marine environments and ecosystems, now and in the future. Such changes occur in environments that already today suffer under pressures from, for example, eutrophication, pollution, shipping, and more. We demonstrate how to implement climate change into regional marine spatial planning by introducing data of future temperature, salinity, and sea ice cover from regional ocean climate model projections to an existing cumulative impact model. This makes it possible to assess climate change impact in relation to pre-existing cumulative impact from current human activities. Results indicate that end-of-century projected climate change alone is a threat of the same magnitude as the combination of all current pressures to the marine environment. These findings give marine planners and policymakers forewarning on how future climate change may impact marine ecosystems, across space, emission scenarios, and in relation to other pressures.
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