| 1. |
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| 2. |
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| 3. |
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| 4. |
- Feroci, M., et al.
(författare)
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The large observatory for x-ray timing
- 2014
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Ingår i: Proceedings of SPIE - The International Society for Optical Engineering. - : SPIE. - 9780819496126
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Konferensbidrag (refereegranskat)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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| 5. |
- 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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| 6. |
- Feroci, M., et al.
(författare)
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LOFT - The large observatory for x-ray timing
- 2012
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Ingår i: Proceedings of SPIE - The International Society for Optical Engineering. - : SPIE - International Society for Optical Engineering. - 9780819491442 ; , s. 84432D-
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Konferensbidrag (refereegranskat)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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| 7. |
- 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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| 8. |
- 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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| 9. |
- 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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| 10. |
- Went, M, et al.
(författare)
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Author Correction: Identification of multiple risk loci and regulatory mechanisms influencing susceptibility to multiple myeloma
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 213-
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Tidskriftsartikel (refereegranskat)abstract
- The original version of this Article contained an error in the spelling of a member of the PRACTICAL Consortium, Manuela Gago-Dominguez, which was incorrectly given as Manuela Gago Dominguez. This has now been corrected in both the PDF and HTML versions of the Article. Furthermore, in the original HTML version of this Article, the order of authors within the author list was incorrect. The PRACTICAL consortium was incorrectly listed after Richard S. Houlston and should have been listed after Nora Pashayan. This error has been corrected in the HTML version of the Article; the PDF version was correct at the time of publication.
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| 11. |
- 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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| 12. |
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| 13. |
- Benavente, ED, et al.
(författare)
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Female gene networks are expressed in myofibroblast-like smooth muscle cells in vulnerable atherosclerotic plaques
- 2023
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Ingår i: bioRxiv : the preprint server for biology. - : Cold Spring Harbor Laboratory.
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Women presenting with coronary artery disease (CAD) more often present with fibrous atherosclerotic plaques, which are currently understudied. Phenotypically modulated smooth muscle cells (SMCs) contribute to atherosclerosis in women. How these phenotypically modulated SMCs shape female versus male plaques is unknown. Here, we show sex-stratified gene regulatory networks (GRNs) from human carotid atherosclerotic tissue. Prioritization of these networks identified two main SMC GRNs in late-stage atherosclerosis. Single-cell RNA-sequencing mapped these GRNs to two SMC phenotypes: a phenotypically modulated myofibroblast-like SMC network and a contractile SMC network. The myofibroblast-like GRN was mostly expressed in plaques that were vulnerable in females. Finally, mice orthologs of the female myofibroblast-like genes showed retained expression in advanced plaques from female mice but were downregulated in male mice during atherosclerosis progression. Female atherosclerosis is driven by GRNs that promote a fibrous vulnerable plaque rich in myofibroblast-like SMCs.
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| 14. |
- Mooij, Wolf M., et al.
(författare)
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Modeling water quality in the Anthropocene : directions for the next-generation aquatic ecosystem models
- 2019
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Ingår i: Current Opinion in Environmental Sustainability. - : Elsevier BV. - 1877-3435 .- 1877-3443. ; 36, s. 85-95
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Forskningsöversikt (refereegranskat)abstract
- Everything changes and nothing stands still (Heraclitus). Here we review three major improvements to freshwater aquatic ecosystem models - and ecological models in general - as water quality scenario analysis tools towards a sustainable future. To tackle the rapid and deeply connected dynamics characteristic of the Anthropocene, we argue for the inclusion of eco-evolutionary, novel ecosystem and social-ecological dynamics. These dynamics arise from adaptive responses in organisms and ecosystems to global environmental change and act at different integration levels and different time scales. We provide reasons and means to incorporate each improvement into aquatic ecosystem models. Throughout this study we refer to Lake Victoria as a microcosm of the evolving novel social-ecological systems of the Anthropocene. The Lake Victoria case clearly shows how interlinked eco-evolutionary, novel ecosystem and social-ecological dynamics are, and demonstrates the need for transdisciplinary research approaches towards global sustainability.
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| 15. |
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| 16. |
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| 17. |
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| 18. |
- De Falco, V., et al.
(författare)
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The transitional millisecond pulsar IGR J18245-2452 during its 2013 outburst at X-rays and soft gamma-rays
- 2017
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 603
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Tidskriftsartikel (refereegranskat)abstract
- IGR J18245-2452/PSR J1824-2452I is one of the rare transitional accreting millisecond X-ray pulsars, showing direct evidence of switches between states of rotation-powered radio pulsations and accretion-powered X-ray pulsations, dubbed transitional pulsars. IGR J18245-2452 with a spin frequency of ∼ 254.3 Hz is the only transitional pulsar so far to have shown a full accretion episode, reaching an X-ray luminosity of ∼ 1037 erg s-1 permitting its discovery with INTEGRAL in 2013. In this paper, we report on a detailed analysis of the data collected with the IBIS/ISGRI and the two JEM-X monitors on-board INTEGRAL at the time of the 2013 outburst. We make use of some complementary data obtained with the instruments on-board XMM-Newton and Swift in order to perform the averaged broad-band spectral analysis of the source in the energy range 0.4-250 keV. We have found that this spectrum is the hardest among the accreting millisecond X-ray pulsars. We improved the ephemeris, now valid across its full outburst, and report the detection of pulsed emission up to ∼ 60 keV in both the ISGRI (10.9σ) and Fermi/GBM (5.9σ) bandpass. The alignment of the ISGRI and Fermi GBM 20-60 keV pulse profiles are consistent at a ∼ 25 μs level. We compared the pulse profiles obtained at soft X-rays with XMM-Newton with the soft γ-ray ones, and derived the pulsed fractions of the fundamental and first harmonic, as well as the time lag of the fundamental harmonic, up to 150 μs, as a function of energy. We report on a thermonuclear X-ray burst detected with INTEGRAL, and using the properties of the previously type-I X-ray burst, we show that all these events are powered primarily by helium ignited at a depth of yign ≈ 2.7 × 108 g cm-2. For such a helium burst the estimated recurrence time of Δtrec ≈ 5.6 d is in agreement with the observations.
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| 19. |
- Glasbey, James, et al.
(författare)
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The impact of conversion on the risk of major complication following laparoscopic colonic surgery : an international, multicentre prospective audit
- 2018
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Ingår i: Colorectal Disease. - : Wiley. - 1462-8910. ; 2020 Suppl 6, s. 69-89
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Laparoscopy has now been implemented as a standard of care for elective colonic resection around the world. During the adoption period, studies showed that conversion may be detrimental to patients, with poorer outcomes than both laparoscopic completed or planned open surgery. The primary aim of this study was to determine whether laparoscopic conversion was associated with a higher major complication rate than planned open surgery in contemporary, international practice.METHODS: Combined analysis of the European Society of Coloproctology 2017 and 2015 audits. Patients were included if they underwent elective resection of a colonic segment from the caecum to the rectosigmoid junction with primary anastomosis. The primary outcome measure was the 30-day major complication rate, defined as Clavien-Dindo grade III-V.RESULTS: Of 3980 patients, 64% (2561/3980) underwent laparoscopic surgery and a laparoscopic conversion rate of 14% (359/2561). The major complication rate was highest after open surgery (laparoscopic 7.4%, converted 9.7%, open 11.6%, P < 0.001). After case mix adjustment in a multilevel model, only planned open (and not laparoscopic converted) surgery was associated with increased major complications in comparison to laparoscopic surgery (OR 1.64, 1.27-2.11, P < 0.001).CONCLUSIONS: Appropriate laparoscopic conversion should not be considered a treatment failure in modern practice. Conversion does not appear to place patients at increased risk of complications vs planned open surgery, supporting broadening of selection criteria for attempted laparoscopy in elective colonic resection.
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| 20. |
- Kuiper, I. N., et al.
(författare)
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Agreement in reporting of asthma by parents or offspring - the RHINESSA generation study
- 2018
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Ingår i: Bmc Pulmonary Medicine. - : Springer Science and Business Media LLC. - 1471-2466. ; 18:122
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Tidskriftsartikel (refereegranskat)abstract
- Background: Self-report questionnaires are commonly used in epidemiology, but may be susceptible to misclassification, especially if answers are given on behalf of others, e.g. children or parents. The aim was to determine agreement and analyse predictors of disagreement in parents' reports of offspring asthma, and in offspring reports of parents' asthma. Methods: In the Respiratory Health in Northern Europe, Spain and Australia (RHINESSA) generation study, 6752 offspring (age range 18-51 years) and their parents (age range 39-66 years) reported their own and each other's asthma status. Agreement between asthma reports from offspring and parents was determined by calculating sensitivity, specificity, positive and negative predictive value and Cohen's kappa. The participants' own answers regarding themselves were defined as the gold standard. To investigate predictors for disagreement logistic regression analyses were performed to obtain odds ratios (OR) with 95% confidence intervals (CI) for sex, smoking status, education, comorbidity and severity of asthma. Results: Agreement was good for parental report of offspring early onset asthma (< 10 years, Cohen's kappa 0.72) and moderate for offspring later onset asthma (Cohen's kappa 0.46). Specificity was 0.99 for both, and sensitivity was 0.68 and 0.36, respectively. For offspring report of maternal and paternal asthma the agreement was good (Cohen's kappa 0.69 and 0.68), specificity was 0.96 and 0.97, and sensitivity was 0.72 and 0.68, respectively. The positive predictive value (PPV) was lowest for offspring report of maternal asthma (0.75), and highest for parents' report of early onset asthma in the offspring (0.83). The negative predictive value (NPV) was high for all four groups (0.94-0.97). In multivariate analyses current smokers (OR = 1.46 [95% CI 1.05, 2.02]) and fathers (OR = 1.31 [95% CI 1. 08, 1.59]) were more likely to report offspring asthma incorrectly. Offspring wheeze was associated with reporting parental asthma incorrectly (OR = 1.60 [95% CI 1.21, 2.11]), both under- and over reporting. Conclusions: Asthma reports across generations show moderate to good agreement, making information from other generations a useful tool in the absence of direct reports.
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| 21. |
- Liang, N, et al.
(författare)
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Hepatocyte-specific loss of GPS2 in mice reduces non-alcoholic steatohepatitis via activation of PPARα
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 1684-
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Tidskriftsartikel (refereegranskat)abstract
- Obesity triggers the development of non-alcoholic fatty liver disease (NAFLD), which involves alterations of regulatory transcription networks and epigenomes in hepatocytes. Here we demonstrate that G protein pathway suppressor 2 (GPS2), a subunit of the nuclear receptor corepressor (NCOR) and histone deacetylase 3 (HDAC3) complex, has a central role in these alterations and accelerates the progression of NAFLD towards non-alcoholic steatohepatitis (NASH). Hepatocyte-specific Gps2 knockout in mice alleviates the development of diet-induced steatosis and fibrosis and causes activation of lipid catabolic genes. Integrative cistrome, epigenome and transcriptome analysis identifies the lipid-sensing peroxisome proliferator-activated receptor α (PPARα, NR1C1) as a direct GPS2 target. Liver gene expression data from human patients reveal that Gps2 expression positively correlates with a NASH/fibrosis gene signature. Collectively, our data suggest that the GPS2-PPARα partnership in hepatocytes coordinates the progression of NAFLD in mice and in humans and thus might be of therapeutic interest.
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| 22. |
- Lu, Chang, et al.
(författare)
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Identification of a gene network driving the attenuated response to lipopolysaccharide of monocytes from hypertensive coronary artery disease patients
- 2024
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Ingår i: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 15
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: The impact of cardiovascular disease (CVD) risk factors, encompassing various biological determinants and unhealthy lifestyles, on the functional dynamics of circulating monocytes—a pivotal cell type in CVD pathophysiology remains elusive. In this study, we aimed to elucidate the influence of CVD risk factors on monocyte transcriptional responses to an infectious stimulus. Methods: We conducted a comparative analysis of monocyte gene expression profiles from the CTMM – CIRCULATING CELLS Cohort of coronary artery disease (CAD) patients, at baseline and after lipopolysaccharide (LPS) stimulation. Gene co-expression analysis was used to identify gene modules and their correlations with CVD risk factors, while pivotal transcription factors controlling the hub genes in these modules were identified by regulatory network analyses. The identified gene module was subjected to a drug repurposing screen, utilizing the LINCS L1000 database. Results: Monocyte responsiveness to LPS showed a highly significant, negative correlation with blood pressure levels (ρ< -0.4; P<10-80). We identified a ZNF12/ZBTB43-driven gene module closely linked to diastolic blood pressure, suggesting that monocyte responses to infectious stimuli, such as LPS, are attenuated in CAD patients with elevated diastolic blood pressure. This attenuation appears associated with a dampening of the LPS-induced suppression of oxidative phosphorylation. Finally, we identified the serine-threonine inhibitor MW-STK33-97 as a drug candidate capable of reversing this aberrant LPS response. Conclusions: Monocyte responses to infectious stimuli may be hampered in CAD patients with high diastolic blood pressure and this attenuated inflammatory response may be reversed by the serine-threonine inhibitor MW-STK33-97. Whether the identified gene module is a mere indicator of, or causal factor in diastolic blood pressure and the associated dampened LPS responses remains to be determined.
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| 23. |
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| 24. |
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| 25. |
- Mooij, Wolf M., et al.
(författare)
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Serving many at once : How a database approach can create unity in dynamical ecosystem modelling
- 2014
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Ingår i: Environmental Modelling & Software. - : Elsevier BV. - 1364-8152 .- 1873-6726. ; 61, s. 266-273
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Tidskriftsartikel (refereegranskat)abstract
- Simulation modelling in ecology is a field that is becoming increasingly compartmentalized. Here we propose a Database Approach To Modelling (DATM) to create unity in dynamical ecosystem modelling with differential equations. In this approach the storage of ecological knowledge is independent of the language and platform in which the model will be run. To create an instance of the model, the information in the database is translated and augmented with the language and platform specifics. This process is automated so that a new instance can be created each time the database is updated. We describe the approach using the simple Lotka-Volterra model and the complex ecosystem model for shallow lakes PCLake, which we automatically implement in the frameworks OSIRIS, GRIND for MATLAB, ACSL, R, DUFLOW and DELWAQ. A clear advantage of working in a database is the overview it provides. The simplicity of the approach only adds to its elegance.
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| 26. |
- Ostergaard, Anna, et al.
(författare)
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The Prognostic Effect of IKZF1 Deletions in ETV6:: RUNX1 and High Hyperdiploid Childhood Acute Lymphoblastic Leukemia
- 2023
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Ingår i: HemaSphere. - 2572-9241. ; 7:5, s. 875-875
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Tidskriftsartikel (refereegranskat)abstract
- IKZF1 deletions are an established prognostic factor in childhood acute lymphoblastic leukemia (ALL). However, their relevance in patients with good risk genetics, namely ETV6::RUNX1 and high hyperdiploid (HeH), ALL remains unclear. We assessed the prognostic impact of IKZF1 deletions in 939 ETV6::RUNX1 and 968 HeH ALL patients by evaluating data from 16 trials from 9 study groups. Only 3% of ETV6::RUNX1 cases (n = 26) were IKZF1-deleted; this adversely affected survival combining all trials (5-year event-free survival [EFS], 79% versus 92%; P = 0.02). No relapses occurred among the 14 patients with an IKZF1 deletion treated on a minimal residual disease (MRD)-guided protocols. Nine percent of HeH cases (n = 85) had an IKZF1 deletion; this adversely affected survival in all trials (5-year EFS, 76% versus 89%; P = 0.006) and in MRD-guided protocols (73% versus 88%; P = 0.004). HeH cases with an IKZF1 deletion had significantly higher end of induction MRD values (P = 0.03). Multivariate Cox regression showed that IKZF1 deletions negatively affected survival independent of sex, age, and white blood cell count at diagnosis in HeH ALL (hazard ratio of relapse rate [95% confidence interval]: 2.48 [1.32-4.66]). There was no evidence to suggest that IKZF1 deletions affected outcome in the small number of ETV6::RUNX1 cases in MRD-guided protocols but that they are related to higher MRD values, higher relapse, and lower survival rates in HeH ALL. Future trials are needed to study whether stratifying by MRD is adequate for HeH patients or additional risk stratification is necessary.
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| 27. |
- Papitto, A., et al.
(författare)
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The INTEGRAL view of the pulsating hard X-ray sky : from accreting and transitional millisecond pulsars to rotation-powered pulsars and magnetars
- 2020
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Ingår i: New astronomy reviews (Print). - : Elsevier BV. - 1387-6473 .- 1872-9630. ; 91
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Tidskriftsartikel (refereegranskat)abstract
- In the last 25 years a new generation of X-ray satellites imparted a significant leap forward in our knowledge of X-ray pulsars. The discovery of accreting and transitional millisecond pulsars proved that disk accretion can spin up a neutron star to a very high rotation speed. The detection of MeV-GeV pulsed emission from a few hundreds of rotation-powered pulsars probed particle acceleration in the outer magnetosphere, or even beyond. Also, a population of two dozens of magnetars has emerged. INTEGRAL played a central role to achieve these results by providing instruments with high temporal resolution up to the hard X-ray/soft, gamma-ray band and a large field of view imager with good angular resolution to spot hard X-ray transients. In this article we review the main contributions by INTEGRAL to our understanding of the pulsating hard X-ray sky, such as the discovery and characterization of several accreting and transitional millisecond pulsars, the generation of the first catalog of hard X-ray/soft gamma-ray rotation-powered pulsars, the detection of polarization in the hard X-ray emission from the Crab pulsar, and the discovery of persistent hard X-ray emission from several magnetars.
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| 28. |
- Pereira, Laura M., et al.
(författare)
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Developing multiscale and integrative nature-people scenarios using the Nature Futures Framework
- 2020
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Ingår i: People and Nature. - : Wiley. - 2575-8314. ; 2:4, s. 1172-1195
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Tidskriftsartikel (refereegranskat)abstract
- 1. Scientists have repeatedly argued that transformative, multiscale global scenarios are needed as tools in the quest to halt the decline of biodiversity and achieve sustainability goals.2. As a first step towards achieving this, the researchers who participated in the scenarios and models expert group of the Intergovernmental Science-Policy Platform on Biodiversity and Ecosystem Services (IPBES) entered into an iterative, participatory process that led to the development of the Nature Futures Framework (NFF).3. The NFF is a heuristic tool that captures diverse, positive relationships of humans with nature in the form of a triangle. It can be used both as a boundary object for continuously opening up more plural perspectives in the creation of desirable nature scenarios and as an actionable framework for developing consistent nature scenarios across multiple scales.4. Here we describe the methods employed to develop the NFF and how it fits into a longer term process to create transformative, multiscale scenarios for nature. We argue that the contribution of the NFF is twofold: (a) its ability to hold a plurality of perspectives on what is desirable, which enables the development of joint goals and visions and recognizes the possible convergence and synergies of measures to achieve these visions and (b), its multiscale functionality for elaborating scenarios and models that can inform decision-making at relevant levels, making it applicable across specific places and perspectives on nature.5. If humanity is to achieve its goal of a more sustainable and prosperous future rooted in a flourishing nature, it is critical to open up a space for more plural perspectives of human-nature relationships. As the global community sets out to develop new goals for biodiversity, the NFF can be used as a navigation tool helping to make diverse, desirable futures possible.
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| 29. |
- Rodin, S, et al.
(författare)
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Clonal culturing of human embryonic stem cells on laminin-521/E-cadherin matrix in defined and xeno-free environment
- 2014
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 5, s. 3195-
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Tidskriftsartikel (refereegranskat)abstract
- Lack of robust methods for establishment and expansion of pluripotent human embryonic stem (hES) cells still hampers development of cell therapy. Laminins (LN) are a family of highly cell-type specific basement membrane proteins important for cell adhesion, differentiation, migration and phenotype stability. Here we produce and isolate a human recombinant LN-521 isoform and develop a cell culture matrix containing LN-521 and E-cadherin, which both localize to stem cell niches in vivo. This matrix allows clonal derivation, clonal survival and long-term self-renewal of hES cells under completely chemically defined and xeno-free conditions without ROCK inhibitors. Neither LN-521 nor E-cadherin alone enable clonal survival of hES cells. The LN-521/E-cadherin matrix allows hES cell line derivation from blastocyst inner cell mass and single blastomere cells without a need to destroy the embryo. This method can facilitate the generation of hES cell lines for development of different cell types for regenerative medicine purposes.
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| 30. |
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| 31. |
- van Gerven, Luuk P. A., et al.
(författare)
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Advantages of concurrent use of multiple software frameworks in water quality modelling using a database approach
- 2015
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Ingår i: Fundamental and Applied Limnology. - : Schweizerbart. - 1863-9135. ; 186:1-2, s. 5-20
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Tidskriftsartikel (refereegranskat)abstract
- Water quality modelling deals with multidisciplinary questions ranging from fundamental to applied. Addressing this broad range of questions requires multiple analysis techniques and therefore multiple frameworks. Through the recently developed database approach to modelling (DATM), it has become possible to run a model in multiple software frameworks without much overhead. Here we apply DATM to the ecosystem model for ditches PCDitch and its twin model for shallow lakes PCLake. Using DATM, we run these models in six frameworks (ACSL, DELWAQ, DUFLOW, GRIND for MATLAB, OSIRIS and R), and report on the possible model analyses with tools provided by each framework. We conclude that the dynamic link between frameworks and models resulting from DATM has the following main advantages: it allows one to use the framework one is familiar with for most model analyses and eases switching between frameworks for complementary model analyses, including the switch between a 0-D and 1-D to 3-D setting. Moreover, the strength of each framework - including runtime performance - can now be easily exploited. We envision that a community-based further development of the concept can contribute to the future development of water quality modelling, not only by addressing multidisciplinary questions but also by facilitating the exchange of models and process formulations within the community of water quality modellers.
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| 32. |
- 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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| 33. |
- Amofah, H. A., et al.
(författare)
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Factors associated with disturbances in sleep-wake pattern in octogenarian patients in the early postoperative phase after surgical 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. S63-S64
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Tidskriftsartikel (refereegranskat)abstract
- Background: Disturbances of the sleep-wake pattern are known phenomenon in the postoperative phase after aortic valve replacement (SAVR) that have negative impact on the morbidity, quality of life and mortality. Octogenarian patients are an increasing group admitted for cardiac surgery, however knowledge is based on younger patients.Aims: To determine factors associated with disturbances in postoperative sleep-wake pattern in octogenarian patients after SAVR.Methods: A prospective cohort study of octogenarian patients in a single center university hospital. Inclusion criteria were age > 80 years, severe aortic stenosis, accepted for SAVR. Actigraphy was used to identify the sleep-wake pattern (sleep-time, sleep efficiency and wake time night and sleep- and wake-time day) for the five first postoperative days, and the sleep questionnaires Minimal Insomnia Symptom scale (MISS) to measure the selfreported insomnia at baseline and daily for the five first postoperative days. Charlsons comorbidity index was used to score comorbidities and the Visual Analog Scale (VAS), was used to rate pain severity. The patients’ medical journals were used to record duration of anesthesia, duration of cardiopulmonary by-pass, blood transfusions and parenteral administration of morphine equivalents. Multiple regression analysis was used to test associations between variables.Results: In all, 78 patients were included (40 women). Mean age was 82 years (SD 2.0). For the sleep-wake pattern first to fifth postoperative night, mean sleep-time night was 330-370 minutes (SD 32-124). Mean sleep efficiency was 68-77% (SD 21-26). Mean sleep-time day was 545-712 minutes (SD 146-169). Mean insomnia score was 1,8-5,3 (SD 2,6-3,8). On the first postoperative night the pain VAS score correlated with wake time night, where a higher VAS indicated more wake time (p=.014, adjusted R2=.213). No other variable; age, gender, duration of anesthesia, duration of cardiopulmonary by-pass, blood transfusion or morphine equivalents showed significant association with the sleep-wake pattern or insomnia.Conclusion: Postoperative pain was associated with disturbances in sleep-wake pattern in octogenarian patients in the early postoperative phase after SAVR. This indicates that pain management may be inadequate for patients after SAVR. More research on this issue is needed to establish data needed to improve treatment and care.
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| 34. |
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| 35. |
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| 36. |
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| 37. |
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| 38. |
- Frantzen, Astri Tafjord, et al.
(författare)
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Frailty Status and Patient-Reported Outcomes in Octogenarians Following Transcatheter or Surgical Aortic Valve Replacement
- 2021
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Ingår i: Heart, Lung and Circulation. - : Elsevier. - 1443-9506 .- 1444-2892. ; 30:8, s. 1221-1231
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundFrailty status and patient-reported outcomes are especially pertinent in octogenarians following transcatheter aortic valve implantation (TAVI) and surgical aortic valve replacement (SAVR) to guide treatment decisions and promote patient-centred care.AimWe aimed to determine if frailty changed 6 months after aortic valve replacement (AVR) in octogenarians, and to describe changes in self-rated health according to frailty status in patients who underwent TAVI or SAVR.MethodIn a prospective cohort study, frailty and self-rated health were measured one day prior to and 6 months after AVR. Frailty status was measured with the Study of Osteoporotic Fracture index. Self-rated health was measured comprehensively with the disease-specific Minnesota Living with Heart Failure Questionnaire, the generic Medical Outcomes Study Short Form-12 questionnaire (SF-12), and two global questions from The World Health Organization Quality of Life Instrument Abbreviated.ResultsData were available for 143 consecutive patients (mean age 83 +/- 2.7 years, 57% women; 45% underwent TAVI). At baseline, 34% were robust, 27% prefrail, and 39% frail. Overall, there was no change in the distribution of frailty status 6 months after baseline (p=0.13). However, on an individual level 65 patients changed frailty status after AVR (40 patients improved and 25 declined). Improvement in frailty status was common in prefrail (33%; n=13) and frail patients (48%; n=27). Patients had improved self-rated health after AVR, with significant differences between frailty states both at baseline (SF-12 physical: 37.4 [robust], 33.1 [prefrail], 31.6 [frail], p=0.03); SF-12 mental: 51.9 [robust], 50.8 [prefrail], 44.5 [frail], p<0.001); and at the 6-month follow-up (SF-12 physical: 45.4 [robust], 38.3 [prefrail], 32.1 [frail], p<0.001); SF-12 mental: 54.9 [robust], 49.6 [prefrail], 46.8 [frail], p=0.002).ConclusionsAdvanced treatment performed in a high-risk population allowed people to improve their self-rated health. Although frailty is associated with poor self-rated health, frailty status does not equal negative outcomes. The frail patients were those who improved most in self-rated physical and mental health. They had the lowest baseline self-rated health scores and had therefore the most to gain.
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| 39. |
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| 40. |
- Gerling, M, et al.
(författare)
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Stromal Hedgehog signalling is downregulated in colon cancer and its restoration restrains tumour growth
- 2016
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7, s. 12321-
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Tidskriftsartikel (refereegranskat)abstract
- A role for Hedgehog (Hh) signalling in the development of colorectal cancer (CRC) has been proposed. In CRC and other solid tumours, Hh ligands are upregulated; however, a specific Hh antagonist provided no benefit in a clinical trial. Here we use Hh reporter mice to show that downstream Hh activity is unexpectedly diminished in a mouse model of colitis-associated colon cancer, and that downstream Hh signalling is restricted to the stroma. Functionally, stroma-specific Hh activation in mice markedly reduces the tumour load and blocks progression of advanced neoplasms, partly via the modulation of BMP signalling and restriction of the colonic stem cell signature. By contrast, attenuated Hh signalling accelerates colonic tumourigenesis. In human CRC, downstream Hh activity is similarly reduced and canonical Hh signalling remains predominantly paracrine. Our results suggest that diminished downstream Hh signalling enhances CRC development, and that stromal Hh activation can act as a colonic tumour suppressor.
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| 41. |
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| 42. |
- Kim, HyeJin, et al.
(författare)
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Towards a better future for biodiversity and people : Modelling Nature Futures
- 2023
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Ingår i: Global Environmental Change. - 0959-3780 .- 1872-9495. ; 82
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Tidskriftsartikel (refereegranskat)abstract
- The Nature Futures Framework (NFF) is a heuristic tool for co-creating positive futures for nature and people. It seeks to open up a diversity of futures through mainly three value perspectives on nature - Nature for Nature, Nature for Society, and Nature as Culture. This paper describes how the NFF can be applied in modelling to support decision-making. First, we describe key considerations for the NFF in developing qualitative and quantitative scenarios: i) multiple value perspectives on nature as a state space where pathways improving nature toward a frontier can be represented, ii) mutually reinforcing key feedbacks of social-ecological systems that are important for nature conservation and human wellbeing, iii) indicators of multiple knowledge systems describing the evolution of complex social-ecological dynamics. We then present three approaches to modelling Nature Futures scenarios in the review, screening, and design phases of policy processes. This paper seeks to facilitate the integration of relational values of nature in models and strengthen modelled linkages across biodiversity, nature's contributions to people, and quality of life.
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| 43. |
- Kuiper, Ingrid Nordeide, et al.
(författare)
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Lung health in adulthood after childhood exposure to air pollution and greenness
- 2018
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Ingår i: European Respiratory Journal. - : European Respiratory Society. - 0903-1936 .- 1399-3003. ; 52
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Little is known on childhood exposure to air pollution and adult chronic respiratory outcomes.Aim: To investigate associations between air pollution and greenness in childhood and adult lung health.Methods: In selected centres of the RHINESSA study (age 18-52) we analysed the outcomes respiratory symptoms (≥3 symptoms), severe wheeze (wheeze last year with breathlessness, no cold) and late onset asthma (>10 years). We calculated mean annual exposures of PM2.5, PM10, NO2 (µg/m³) and greenness (Normalized Difference Vegetation Index, 100m buffer) from offspring's birth till age 18, categorised into mean exposure <10 years and 11-18 years. We performed multilevel logistic regression clustered by family, stratified by centre and adjusted for childhood passive smoke and parental asthma.Results: 12% had ≥3 respiratory symptoms, 7.7% severe wheeze, and 9.4% late onset asthma. Overall estimates: greenness was associated with less respiratory symptoms, PM2.5 and NO2 with more late onset asthma. Exposure <10 years: Greenness was associated with less wheeze in Tartu (OR 0.29, 95%CI 0.11-0.73). PM2.5 (OR 1.22, 95%CI 1.00-1.48) and NO2 (OR 1.06, 95%CI 1.01-1.11) were risk factors for late onset asthma in Bergen. PM10 was a risk factor for respiratory symptoms (OR 1.21, 95%CI 1.04-1.41) in Uppsala and late onset asthma (OR 1.23, 95%CI 1.02-1.45) in Bergen. Exposure 11-18 years: Greenness was protective for respiratory symptoms (OR 0.29, 95%CI 0.10-0.86) and wheeze (OR 0.39, 95%CI 0.19-0.80) in Tartu.Conclusions: Childhood exposure to greenness was associated with less respiratory symptoms, while air pollutants were associated with more respiratory symptoms (some centres) and late onset asthma.
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| 44. |
- Kuiper, L., et al.
(författare)
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High-energy characteristics of the accretion-powered millisecond pulsar IGR J17591-2342 during its 2018 outburst : XMM-Newton, NICER, NuSTAR, and INTEGRAL view of the 0.3-300 keV X-ray band
- 2020
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Ingår i: Astronomy and Astrophysics. - : EDP SCIENCES S A. - 0004-6361 .- 1432-0746. ; 641
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Tidskriftsartikel (refereegranskat)abstract
- IGR J17591-2342 is an accreting millisecond X-ray pulsar, discovered with INTEGRAL, which went into outburst around July 21, 2018. To better understand the physics acting in these systems during the outburst episode, we performed detailed temporal-, timing-, and spectral analyses across the 0.3-300 keV band using data from NICER, XMM-Newton, NuSTAR, and INTEGRAL. The hard X-ray 20-60 keV outburst profile covering similar to 85 days is composed of four flares. Over the course of the maximum of the last flare, we discovered a type-I thermonuclear burst in INTEGRAL JEM-X data, posing constraints on the source distance. We derived a distance of 7.6 +/- 0.7 kpc, adopting Eddington-limited photospheric radius expansion and assuming anisotropic emission. In the timing analysis, using all NICER 1-10 keV monitoring data, we observed a rather complex set of behaviours starting with a spin-up period (MJD 58345-58364), followed by a frequency drop (MJD 58364-58370), an episode of constant frequency (MJD 58370-58383), concluded by irregular behaviour till the end of the outburst. The 1-50 keV phase distributions of the pulsed emission, detected up to similar to 120 keV using INTEGRAL ISGRI data, was decomposed in three Fourier harmonics showing that the pulsed fraction of the fundamental increases from similar to 10% to similar to 17% going from similar to 1.5 to similar to 4 keV, while the harder photons arrive earlier than the soft photons for energies less than or similar to 10 keV. The total emission spectrum of IGR J17591-2342 across the 0.3-150 keV band could adequately be fitted in terms of an absorbed COMPPS model yielding as best fit parameters a column density of N-H=(2.09 +/- 0.05) x 10(22) cm(-2), a blackbody seed photon temperature kT(bb, seed) of 0.64 +/- 0.02 keV, electron temperature kT(e)=38.8 +/- 1.2 keV and Thomson optical depth tau (T)=1.59 +/- 0.04. The fit normalisation results in an emission area radius of 11.3 +/- 0.5 km adopting a distance of 7.6 kpc. Finally, the results are discussed within the framework of accretion physics- and X-ray thermonuclear burst theory.
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| 45. |
- Li, Z., et al.
(författare)
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Mixed H/He bursts in SAX J1748.9-2021 during the spectral change of its 2015 outburst
- 2018
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 620
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Tidskriftsartikel (refereegranskat)abstract
- SAX J1748.9-2021 is a transiently accreting X-ray millisecond pulsar. It is also known as an X-ray burster source discovered by Beppo-SAX. We analyzed the persistent emission and type-I X-ray burst properties during its 2015 outburst. The source changed from hard to soft state within half day. We modeled the broadband spectra of the persistent emission in the (1-250) keV energy band for both spectral states using the quasi-simultaneous INTEGRAL and Swift data. The broadband spectra are well fitted by an absorbed thermal Componization model, COMPPS, in a slab geometry. The best-fits for the two states indicate significantly different plasma temperature of 18 and 5 keV and the Thomson optical depths of three and four, respectively. In total, 56 type-I X-ray bursts were observed during the 2015 outburst, of which 26 detected by INTEGRAL in the hard state, 25 by XMM-Newton in the soft state, and five by Swift in both states. As the object transited from the hard to the soft state, the recurrence time for X-ray bursts decreased from approximate to 2 to approximate to 1 h. The relation between the recurrence time, Delta t(rec )and the local mass accretion rate per unit area onto the compact object, in, is fitted by a power-law model, and yielded as best fit at Delta t(rec )similar to <(m) over dot >(-1)(.0)(2 +/-)(0.)(03) using all X-ray bursts. In both cases, the observed recurrence times are consistent with the mixed hydrogen and helium bursts. We also discuss the effects of type-I X-ray bursts prior to the hard to soft transition.
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| 46. |
- Li, Z. S., et al.
(författare)
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Broadband X-ray spectra and timing of the accreting millisecond pulsar Swift J1756.9-2508 during its 2018 and 2019 outbursts
- 2021
-
Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 649
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Tidskriftsartikel (refereegranskat)abstract
- The accreting millisecond X-ray pulsar Swift J1756.9-2508 launched into an outburst in April 2018 and June 2019 - 8.7 years after the previous period of activity. We investigated the temporal, timing, and spectral properties of these two outbursts using data from NICER, XMM-Newton, NuSTAR, INTEGRAL, Swift, and Insight-HXMT. The two outbursts exhibited similar broadband spectra and X-ray pulse profiles. For the first time, we report the detection of the pulsed emission up to similar to 100 keV that was observed by Insight-HXMT during the 2018 outburst. We also found the pulsation up to similar to 60 keV that was observed by NICER and NuSTAR during the 2019 outburst. We performed a coherent timing analysis combining the data from the two outbursts. The binary system is well described by a constant orbital period over a time span of similar to 12 years. The time-averaged broadband spectra are well fitted by the absorbed thermal Comptonization model COMPPS in a slab geometry with an electron temperature, kT(e)=40-50 keV, Thomson optical depth tau similar to 1.3, blackbody seed photon temperature kT(bb, seed)similar to 0.7-0.8 keV, and hydrogen column density of N-H similar to 4.2x10(22) cm(-2). We searched the available data for type-I (thermonuclear) X-ray bursts, but found none, which is unsurprising given the estimated low peak accretion rate (approximate to 0.05 of the Eddington rate) and generally low expected burst rates for hydrogen-poor fuel. Based on the history of four outbursts to date, we estimate the long-term average accretion rate at roughly 5x10(-12) M-circle dot yr(-1) for an assumed distance of 8 kpc. The expected mass transfer rate driven by gravitational radiation in the binary implies the source may be no closer than 4 kpc. Swift J1756.9-2508 is the third low mass X-ray binary exhibiting "double" outbursts, which are separated by much shorter intervals than what we typically see and are likely to result from interruption of the accretion flow from the disk onto the neutron star. Such behavior may have important implications for the disk instability model.
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| 47. |
- Nilsson, R. Jonas A., et al.
(författare)
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Rearranged EML4-ALK fusion transcripts sequester in circulating blood platelets and enable blood-based crizotinib response monitoring in non-small-cell lung cancer
- 2016
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Ingår i: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 7:1, s. 1066-1075
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Non-small-cell lung cancers harboring EML4-ALK rearrangements are sensitive to crizotinib. However, despite initial response, most patients will eventually relapse, and monitoring EML4-ALK rearrangements over the course of treatment may help identify these patients. However, challenges associated with serial tumor biopsies have highlighted the need for blood-based assays for the monitoring of biomarkers. Platelets can sequester RNA released by tumor cells and are thus an attractive source for the non-invasive assessment of biomarkers. Methods: EML4-ALK rearrangements were analyzed by RT-PCR in platelets and plasma isolated from blood obtained from 77 patients with non-small-cell lung cancer, 38 of whom had EML4-ALK-rearranged tumors. In a subset of 29 patients with EML4-ALK-rearranged tumors who were treated with crizotinib, EML4-ALK rearrangements in platelets were correlated with progression-free and overall survival. Results: RT-PCR demonstrated 65% sensitivity and 100% specificity for the detection of EML4-ALK rearrangements in platelets. In the subset of 29 patients treated with crizotinib, progression-free survival was 3.7 months for patients with EML4-ALK+ platelets and 16 months for those with EML4-ALK- platelets (hazard ratio, 3.5; P = 0.02). Monitoring of EML4-ALK rearrangements in the platelets of one patient over a period of 30 months revealed crizotinib resistance two months prior to radiographic disease progression. Conclusions: Platelets are a valuable source for the non-invasive detection of EML4-ALK rearrangements and may prove useful for predicting and monitoring outcome to crizotinib, thereby improving clinical decisions based on radiographic imaging alone.
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| 48. |
- Paz Duran, América, et al.
(författare)
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Bringing the Nature Futures Framework to life : creating a set of illustrative narratives of nature futures
- 2023
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Ingår i: Sustainability Science. - 1862-4065 .- 1862-4057.
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Tidskriftsartikel (refereegranskat)abstract
- To halt further destruction of the biosphere, most people and societies around the globe need to transform their relationships with nature. The internationally agreed vision under the Convention of Biological Diversity—Living in harmony with nature—is that “By 2050, biodiversity is valued, conserved, restored and wisely used, maintaining ecosystem services, sustaining a healthy planet and delivering benefits essential for all people”. In this context, there are a variety of debates between alternative perspectives on how to achieve this vision. Yet, scenarios and models that are able to explore these debates in the context of “living in harmony with nature” have not been widely developed. To address this gap, the Nature Futures Framework has been developed to catalyse the development of new scenarios and models that embrace a plurality of perspectives on desirable futures for nature and people. In this paper, members of the IPBES task force on scenarios and models provide an example of how the Nature Futures Framework can be implemented for the development of illustrative narratives representing a diversity of desirable nature futures: information that can be used to assess and develop scenarios and models whilst acknowledging the underpinning value perspectives on nature. Here, the term illustrative reflects the multiple ways in which desired nature futures can be captured by these narratives. In addition, to explore the interdependence between narratives, and therefore their potential to be translated into scenarios and models, the six narratives developed here were assessed around three areas of the transformative change debate, specifically, (1) land sparing vs. land sharing, (2) Half Earth vs. Whole Earth conservation, and (3) green growth vs. post-growth economic development. The paper concludes with an assessment of how the Nature Futures Framework could be used to assist in developing and articulating transformative pathways towards desirable nature futures.
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| 49. |
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| 50. |
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