1. |
- Niemi, MEK, et al.
(author)
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- 2021
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swepub:Mat__t
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2. |
- Feroci, M., et al.
(author)
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The large observatory for x-ray timing
- 2014
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In: Proceedings of SPIE - The International Society for Optical Engineering. - : SPIE. - 9780819496126
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Conference paper (peer-reviewed)abstract
- The Large Observatory For x-ray Timing (LOFT) was studied within ESA M3 Cosmic Vision framework and participated in the final downselection for a launch slot in 2022-2024. Thanks to the unprecedented combination of effective area and spectral resolution of its main instrument, LOFT will study the behaviour of matter under extreme conditions, such as the strong gravitational field in the innermost regions of accretion flows close to black holes and neutron stars, and the supranuclear densities in the interior of neutron stars. The science payload is based on a Large Area Detector (LAD, 10 m2 effective area, 2-30 keV, 240 eV spectral resolution, 1° collimated field of view) and a Wide Field Monitor (WFM, 2-50 keV, 4 steradian field of view, 1 arcmin source location accuracy, 300 eV spectral resolution). The WFM is equipped with an on-board system for bright events (e.g. GRB) localization. The trigger time and position of these events are broadcast to the ground within 30 s from discovery. In this paper we present the status of the mission at the end of its Phase A study.
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3. |
- Feroci, M., et al.
(author)
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LOFT - The large observatory for x-ray timing
- 2012
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In: Proceedings of SPIE - The International Society for Optical Engineering. - : SPIE - International Society for Optical Engineering. - 9780819491442 ; , s. 84432D-
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Conference paper (peer-reviewed)abstract
- The LOFT mission concept is one of four candidates selected by ESA for the M3 launch opportunity as Medium Size missions of the Cosmic Vision programme. The launch window is currently planned for between 2022 and 2024. LOFT is designed to exploit the diagnostics of rapid X-ray flux and spectral variability that directly probe the motion of matter down to distances very close to black holes and neutron stars, as well as the physical state of ultradense matter. These primary science goals will be addressed by a payload composed of a Large Area Detector (LAD) and a Wide Field Monitor (WFM). The LAD is a collimated (<1 degree field of view) experiment operating in the energy range 2-50 keV, with a 10 m2 peak effective area and an energy resolution of 260 eV at 6 keV. The WFM will operate in the same energy range as the LAD, enabling simultaneous monitoring of a few-steradian wide field of view, with an angular resolution of <5 arcmin. The LAD and WFM experiments will allow us to investigate variability from submillisecond QPO's to yearlong transient outbursts. In this paper we report the current status of the project.
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4. |
- Feroci, M., et al.
(author)
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The Large Observatory for X-ray Timing (LOFT)
- 2012
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In: Experimental Astronomy. - : Springer Science and Business Media LLC. - 0922-6435 .- 1572-9508. ; 34:2, s. 415-444
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Journal article (peer-reviewed)abstract
- High-time-resolution X-ray observations of compact objects provide direct access to strong-field gravity, to the equation of state of ultradense matter and to black hole masses and spins. A 10 m(2)-class instrument in combination with good spectral resolution is required to exploit the relevant diagnostics and answer two of the fundamental questions of the European Space Agency (ESA) Cosmic Vision Theme "Matter under extreme conditions", namely: does matter orbiting close to the event horizon follow the predictions of general relativity? What is the equation of state of matter in neutron stars? The Large Observatory For X-ray Timing (LOFT), selected by ESA as one of the four Cosmic Vision M3 candidate missions to undergo an assessment phase, will revolutionise the study of collapsed objects in our galaxy and of the brightest supermassive black holes in active galactic nuclei. Thanks to an innovative design and the development of large-area monolithic silicon drift detectors, the Large Area Detector (LAD) on board LOFT will achieve an effective area of similar to 12 m(2) (more than an order of magnitude larger than any spaceborne predecessor) in the 2-30 keV range (up to 50 keV in expanded mode), yet still fits a conventional platform and small/medium-class launcher. With this large area and a spectral resolution of < 260 eV, LOFT will yield unprecedented information on strongly curved spacetimes and matter under extreme conditions of pressure and magnetic field strength.
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5. |
- Milillo, A., et al.
(author)
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Investigating Mercury's Environment with the Two-Spacecraft BepiColombo Mission
- 2020
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In: Space Science Reviews. - : Springer Science and Business Media LLC. - 0038-6308 .- 1572-9672. ; 216:5
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Research review (peer-reviewed)abstract
- The ESA-JAXA BepiColombo mission will provide simultaneous measurements from two spacecraft, offering an unprecedented opportunity to investigate magnetospheric and exospheric dynamics at Mercury as well as their interactions with the solar wind, radiation, and interplanetary dust. Many scientific instruments onboard the two spacecraft will be completely, or partially devoted to study the near-space environment of Mercury as well as the complex processes that govern it. Many issues remain unsolved even after the MESSENGER mission that ended in 2015. The specific orbits of the two spacecraft, MPO and Mio, and the comprehensive scientific payload allow a wider range of scientific questions to be addressed than those that could be achieved by the individual instruments acting alone, or by previous missions. These joint observations are of key importance because many phenomena in Mercury's environment are highly temporally and spatially variable. Examples of possible coordinated observations are described in this article, analysing the required geometrical conditions, pointing, resolutions and operation timing of different BepiColombo instruments sensors.
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7. |
- Hejnol, A, et al.
(author)
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Assessing the root of bilaterian animals with scalable phylogenomic methods
- 2009
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In: Proceedings of the Royal Society B. ; 276:1677, s. 4261-4270
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Journal article (peer-reviewed)abstract
- A clear picture of animal relationships is a prerequisite to understand how the morphological and ecological diversity of animals evolved over time. Among others, the placement of the acoelomorph flatworms, Acoela and Nemertodermatida, has fundamental implications for the origin and evolution of various animal organ systems. Their position, however, has been inconsistent in phylogenetic studies using one or several genes. Furthermore, Acoela has been among the least stable taxa in recent animal phylogenomic analyses, which simultaneously examine many genes from many species, while Nemertodermatida has not been sampled in any phylogenomic study. New sequence data are presented here from organisms targeted for their instability or lack of representation in prior analyses, and are analysed in combination with other publicly available data. We also designed new automated explicit methods for identifying and selecting common genes across different species, and developed highly optimized supercomputing tools to reconstruct relationships from gene sequences. The results of the work corroborate several recently established findings about animal relationships and provide new support for the placement of other groups. These new data and methods strongly uphold previous suggestions that Acoelomorpha is sister clade to all other bilaterian animals, find diminishing evidence for the placement of the enigmatic Xenoturbella within Deuterostomia, and place Cycliophora with Entoprocta and Ectoprocta. The work highlights the implications that these arrangements have for metazoan evolution and permits a clearer picture of ancestral morphologies and life histories in the deep past.
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8. |
- Naeem, Aishath, et al.
(author)
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Pirtobrutinib targets BTK C481S in ibrutinib-resistant CLL but second-site BTK mutations lead to resistance
- 2023
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In: Blood Advances. - : American Society of Hematology. - 2473-9529 .- 2473-9537. ; 7:9, s. 1929-1943
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Journal article (peer-reviewed)abstract
- Covalent inhibitors of Bruton tyrosine kinase (BTK) have transformed the therapy of chronic lymphocytic leukemia (CLL), but continuous therapy has been complicated by the development of resistance. The most common resistance mechanism in patients whose disease progresses on covalent BTK inhibitors (BTKis) is a mutation in the BTK 481 cysteine residue to which the inhibitors bind covalently. Pirtobrutinib is a highly selective, noncovalent BTKi with substantial clinical activity in patients whose disease has progressed on covalent BTKi, regardless of BTK mutation status. Using in vitro ibrutinib-resistant models and cells from patients with CLL, we show that pirtobrutinib potently inhibits BTK-mediated functions including B-cell receptor (BCR) signaling, cell viability, and CCL3/CCL4 chemokine production in both BTK wild-type and C481S mutant CLL cells. We demonstrate that primary CLL cells from responding patients on the pirtobrutinib trial show reduced BCR signaling, cell survival, and CCL3/CCL4 chemokine secretion. At time of progression, these primary CLL cells show increasing resistance to pirtobrutinib in signaling inhibition, cell viability, and cytokine production. We employed longitudinal whole-exome sequencing on 2 patients whose disease progressed on pirtobrutinib and identified selection of alternative-site BTK mutations, providing clinical evidence that secondary BTK mutations lead to resistance to noncovalent BTKis.
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9. |
- van der Brug, MP, et al.
(author)
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RNA binding activity of the recessive parkinsonism protein DJ-1 supports involvement in multiple cellular pathways
- 2008
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In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490. ; 105:29, s. 10244-10249
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Journal article (peer-reviewed)abstract
- Parkinson's disease (PD) is a major neurodegenerative condition with several rare Mendelian forms. Oxidative stress and mitochondrial function have been implicated in the pathogenesis of PD but the molecular mechanisms involved in the degeneration of neurons remain unclear. DJ-1 mutations are one cause of recessive parkinsonism, but this gene is also reported to be involved in cancer by promoting Ras signaling and suppressing PTEN-induced apoptosis. The specific function of DJ-1 is unknown, although it is responsive to oxidative stress and may play a role in the maintenance of mitochondria. Here, we show, using four independent methods, that DJ-1 associates with RNA targets in cells and the brain, including mitochondrial genes, genes involved in glutathione metabolism, and members of the PTEN/PI3K cascade. Pathogenic recessive mutants are deficient in this activity. We show that DJ-1 is sufficient for RNA binding at nanomolar concentrations. Further, we show that DJ-1 binds RNA but dissociates after oxidative stress. These data implicate a single mechanism for the pleiotropic effects of DJ-1 in different model systems, namely that the protein binds multiple RNA targets in an oxidation-dependent manner.
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10. |
- Dunn, Casey W, et al.
(author)
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Broad phylogenomic sampling improves resolution of the animal tree of life.
- 2008
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In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 452:7188, s. 745-9
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Journal article (peer-reviewed)abstract
- Long-held ideas regarding the evolutionary relationships among animals have recently been upended by sometimes controversial hypotheses based largely on insights from molecular data. These new hypotheses include a clade of moulting animals (Ecdysozoa) and the close relationship of the lophophorates to molluscs and annelids (Lophotrochozoa). Many relationships remain disputed, including those that are required to polarize key features of character evolution, and support for deep nodes is often low. Phylogenomic approaches, which use data from many genes, have shown promise for resolving deep animal relationships, but are hindered by a lack of data from many important groups. Here we report a total of 39.9 Mb of expressed sequence tags from 29 animals belonging to 21 phyla, including 11 phyla previously lacking genomic or expressed-sequence-tag data. Analysed in combination with existing sequences, our data reinforce several previously identified clades that split deeply in the animal tree (including Protostomia, Ecdysozoa and Lophotrochozoa), unambiguously resolve multiple long-standing issues for which there was strong conflicting support in earlier studies with less data (such as velvet worms rather than tardigrades as the sister group of arthropods), and provide molecular support for the monophyly of molluscs, a group long recognized by morphologists. In addition, we find strong support for several new hypotheses. These include a clade that unites annelids (including sipunculans and echiurans) with nemerteans, phoronids and brachiopods, molluscs as sister to that assemblage, and the placement of ctenophores as the earliest diverging extant multicellular animals. A single origin of spiral cleavage (with subsequent losses) is inferred from well-supported nodes. Many relationships between a stable subset of taxa find strong support, and a diminishing number of lineages remain recalcitrant to placement on the tree.
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13. |
- Karlsson, Maths, 1978, et al.
(author)
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Structure of Proton-Conducting Alkali Thio-Hydroxogermanates
- 2008
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In: Chemistry of Materials. - : American Chemical Society (ACS). - 1520-5002 .- 0897-4756. ; 20:19, s. 6014-6021
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Journal article (peer-reviewed)abstract
- Using a combination of neutron diffraction, infrared spectroscopy, and first-principles calculations, we have investigated the structure of hydrated and dehydrated proton conducting alkali thio-hydroxogermanates of general formula M2GeS2(OH)2·yH2O (M = K, Rb, and Cs). The results show that the structure of hydrated and dry materials are basically the same, which confirms previous indications that the main effect of heating these materials is just a loss of water. We suggest that in the hydrated state the structure of these materials is built of dimers of thio-hydroxogermanate anions, with the water molecules acting as bridges between such dimers. In the dehydrated structure, the thio-hydroxogermanate anions instead form an extended network through the formation of interdimer hydrogen bonds through the −OH groups in the structure. The alkali ions are suggested to act as “space-fillers” in voids formed by the thio-hydroxogermanate anion dimers, in both the hydrated and the dehydrated state.
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