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- Feroci, M., et al.
(författare)
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The Large Observatory for X-ray Timing (LOFT)
- 2012
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Ingår i: Experimental Astronomy. - : Springer Science and Business Media LLC. - 0922-6435 .- 1572-9508. ; 34:2, s. 415-444
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Tidskriftsartikel (refereegranskat)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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- Hermsen, W., et al.
(författare)
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Synchronous X-ray and Radio Mode Switches: A Rapid Global Transformation of the Pulsar Magnetosphere
- 2013
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 339:6118, s. 436-439
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Tidskriftsartikel (refereegranskat)abstract
- Pulsars emit from low-frequency radio waves up to high-energy gamma-rays, generated anywhere from the stellar surface out to the edge of the magnetosphere. Detecting correlated mode changes across the electromagnetic spectrum is therefore key to understanding the physical relationship among the emission sites. Through simultaneous observations, we detected synchronous switching in the radio and x-ray emission properties of PSR B0943+10. When the pulsar is in a sustained radio-"bright" mode, the x-rays show only an unpulsed, nonthermal component. Conversely, when the pulsar is in a radio-"quiet" mode, the x-ray luminosity more than doubles and a 100% pulsed thermal component is observed along with the nonthermal component. This indicates rapid, global changes to the conditions in the magnetosphere, which challenge all proposed pulsar emission theories.
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- Menden, MP, et al.
(författare)
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Community assessment to advance computational prediction of cancer drug combinations in a pharmacogenomic screen
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 2674-
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Tidskriftsartikel (refereegranskat)abstract
- The effectiveness of most cancer targeted therapies is short-lived. Tumors often develop resistance that might be overcome with drug combinations. However, the number of possible combinations is vast, necessitating data-driven approaches to find optimal patient-specific treatments. Here we report AstraZeneca’s large drug combination dataset, consisting of 11,576 experiments from 910 combinations across 85 molecularly characterized cancer cell lines, and results of a DREAM Challenge to evaluate computational strategies for predicting synergistic drug pairs and biomarkers. 160 teams participated to provide a comprehensive methodological development and benchmarking. Winning methods incorporate prior knowledge of drug-target interactions. Synergy is predicted with an accuracy matching biological replicates for >60% of combinations. However, 20% of drug combinations are poorly predicted by all methods. Genomic rationale for synergy predictions are identified, including ADAM17 inhibitor antagonism when combined with PIK3CB/D inhibition contrasting to synergy when combined with other PI3K-pathway inhibitors in PIK3CA mutant cells.
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- Greiner, J., et al.
(författare)
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GRIPS - Gamma-Ray Imaging, Polarimetry and Spectroscopy
- 2012
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Ingår i: Experimental astronomy. - : Springer Science and Business Media LLC. - 0922-6435 .- 1572-9508. ; 34:2, s. 551-582
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Tidskriftsartikel (refereegranskat)abstract
- We propose to perform a continuously scanning all-sky survey from 200 keV to 80 MeV achieving a sensitivity which is better by a factor of 40 or more compared to the previous missions in this energy range (COMPTEL, INTEGRAL; see Fig. 1). These gamma-ray observations will be complemented by observations in the soft X-ray and (near-)infrared region with the corresponding telescopes placed on a separate satellite. The Gamma-Ray Imaging, Polarimetry and Spectroscopy ("GRIPS") mission with its three instruments Gamma-Ray Monitor (GRM), X-Ray Monitor (XRM) and InfraRed Telescope (IRT) addresses fundamental questions in ESA's Cosmic Vision plan. Among the major themes of the strategic plan, GRIPS has its focus on the evolving, violent Universe, exploring a unique energy window. We propose to investigate γ-ray bursts and blazars, the mechanisms behind supernova explosions, nucleosynthesis and spallation, the enigmatic origin of positrons in our Galaxy, and the nature of radiation processes and particle acceleration in extreme cosmic sources including pulsars and magnetars. The natural energy scale for these non-thermal processes is of the order of MeV. Although they can be partially and indirectly studied using other methods, only the proposed GRIPS measurements will provide direct access to their primary photons. GRIPS will be a driver for the study of transient sources in the era of neutrino and gravitational wave observatories such as IceCUBE and LISA, establishing a new type of diagnostics in relativistic and nuclear astrophysics. This will support extrapolations to investigate star formation, galaxy evolution, and black hole formation at high redshifts.
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- Hilson, P., et al.
(författare)
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Versatile gene-specific sequence tags for Arabidopsis functional genomics : Trancript profiling and reverse genetics applications
- 2004
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Ingår i: Genome Research. - : Cold Spring Harbor Laboratory. - 1088-9051 .- 1549-5469. ; 14:10B, s. 2176-2189
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Tidskriftsartikel (refereegranskat)abstract
- Microarray transcript profiling and RNA interference are two new technologies crucial for large-scale gene function studies in multicellular eukaryotes. Both rely on sequence-specific hybridization between complementary nucleic acid strands, inciting us to create a collection of gene-specific sequence tags (GSTs) representing at least 21,500 Arabidopsis genes and which are compatible with both approaches. The GSTs were carefully selected to ensure that each of them shared no significant similarity with any other region in the Arabidopsis genome. They were synthesized by PCR amplification from genomic DNA. Spotted microarrays fabricated from the GSTs show good dynamic range, specificity, and sensitivity in transcript profiling experiments. The GSTs have also been transferred to bacterial plasmid vectors via recombinational cloning protocols. These cloned GSTs constitute the ideal starting point for a variety of functional approaches, including reverse genetics. We have subcloned GSTs on a large scale into vectors designed for gene silencing in plant cells. We show that in planta expression of GST hairpin RNA results in the expected phenotypes in silenced Arabidopsis lines. These versatile GST resources provide novel and powerful tools for functional genomics.
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- Marleau, G.-D., et al.
(författare)
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Accreting protoplanets : Spectral signatures and magnitude of gas and dust extinction at H α
- 2022
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 657
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Tidskriftsartikel (refereegranskat)abstract
- Context. Accreting planetary-mass objects have been detected at H α, but targeted searches have mainly resulted in non-detections. Accretion tracers in the planetary-mass regime could originate from the shock itself, making them particularly susceptible to extinction by the accreting material. High-resolution (R > 50 000) spectrographs operating at H α should soon enable one to study how the incoming material shapes the line profile.Aims. We calculate how much the gas and dust accreting onto a planet reduce the H α flux from the shock at the planetary surface and how they affect the line shape. We also study the absorption-modified relationship between the H α luminosity and accretion rate.Methods. We computed the high-resolution radiative transfer of the H α line using a one-dimensional velocity–density–temperature structure for the inflowing matter in three representative accretion geometries: spherical symmetry, polar inflow, and magnetospheric accretion. For each, we explored the wide relevant ranges of the accretion rate and planet mass. We used detailed gas opacities and carefully estimated possible dust opacities.Results. At accretion rates of Ṁ ≲ 3 × 10−6 MJ yr−1, gas extinction is negligible for spherical or polar inflow and at most AH α ≲ 0.5 mag for magnetospheric accretion. Up to Ṁ ≈ 3 × 10−4 MJ yr−1, the gas contributes AH α ≲ 4 mag. This contribution decreases with mass. We estimate realistic dust opacities at H α to be κ ~ 0.01–10 cm2 g−1, which is 10–104 times lower than in the interstellar medium. Extinction flattens the LH α –Ṁ relationship, which becomes non-monotonic with a maximum luminosity LH α ~ 10−4 L⊙ towards Ṁ ≈ 10−4 MJ yr−1 for a planet mass ~10 MJ. In magnetospheric accretion, the gas can introduce features in the line profile, while the velocity gradient smears them out in other geometries.Conclusions. For a wide part of parameter space, extinction by the accreting matter should be negligible, simplifying the interpretation of observations, especially for planets in gaps. At high Ṁ, strong absorption reduces the H α flux, and some measurements can be interpreted as two Ṁ values. Highly resolved line profiles (R ~ 105) can provide (complex) constraints on the thermal and dynamical structure of the accretion flow.
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- Amofah, H. A., et al.
(författare)
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Factors affecting in-hospital sleep-wake pattern in octogenarians during the early postoperative phase after transcutaneous aortic valve replacement
- 2017
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Ingår i: European Journal of Cardiovascular Nursing. - : Sage Publications. - 1474-5151 .- 1873-1953. ; 16:Suppl. 1, s. S53-S53
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Tidskriftsartikel (refereegranskat)abstract
- Background: Octogenarian patients are an increasing group admitted for advanced cardiac treatment. Little is known about factors disturbing their sleep-wake pattern in the early postoperative phase after transcutaneous aortic valve replacement (TAVI), as current knowledge is based upon studies on younger age groups treated for surgical aortic valve replacement.Aim: To determine factors affecting the in-hospital sleep wake pattern in octogenarian patients after TAVI.Methods: This is a prospective cohort study in a tertiary university hospital. Inclusion criteria were age > 80 years with severe aortic stenosis accepted for TAVI. Actigraphy was used to identify sleep-wake pattern (sleep time night and sleep time day), and the Minimal Insomnia Symptom Scale (MISS) to measure self-reported insomnia daily during the first five postoperative days. Charlson`s comorbidity index was used as a measure of comorbidities and the Visual Analog Scale (VAS) to rate pain severity. Information regarding duration of anesthesia, blood transfusion and parenteral administration of morphine equivalents were derived from the patients’ medical journals. Multiple regression analysis was used to test associations between variables.Results: In all, 65 patients (41 women) were included. Mean age was 85 years (SD 2.8). No significant associations were found between age, comorbidities, blood transfusion and morphine equivalents and sleep. Gender was significantly associated with sleep time night and sleep efficiency as men had shortest duration of sleep from the third to the fifth postoperative night (p < .001, and adjusted R2=.230 to .283). Duration of anesthesia had a significant association with sleep time night and sleep efficiency from the third to the fifth postoperative night (p=.013 to p < .001, and adjusted R2=.230 to .283), where longer duration gave less total sleep and lower sleep efficiency. VAS score correlated with wake time night the third night, where a higher VAS score gave more wake time (p=.006 and adjusted R2 .236).Conclusion: Male gender, longer duration of perioperative anesthesia and postoperative pain were associated with disturbances in the postoperative sleep-wake pattern in octogenarian patients in the early postoperative phase after TAVI. This knowledge is important and relevant and should have implications in improving patient care.
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