| 1. |
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- 2019
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Tidskriftsartikel (refereegranskat)
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| 2. |
- Hudson, Lawrence N, et al.
(författare)
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The database of the PREDICTS (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems) project
- 2017
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Ingår i: Ecology and Evolution. - : John Wiley & Sons. - 2045-7758. ; 7:1, s. 145-188
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Tidskriftsartikel (refereegranskat)abstract
- The PREDICTS project-Projecting Responses of Ecological Diversity In Changing Terrestrial Systems (www.predicts.org.uk)-has collated from published studies a large, reasonably representative database of comparable samples of biodiversity from multiple sites that differ in the nature or intensity of human impacts relating to land use. We have used this evidence base to develop global and regional statistical models of how local biodiversity responds to these measures. We describe and make freely available this 2016 release of the database, containing more than 3.2 million records sampled at over 26,000 locations and representing over 47,000 species. We outline how the database can help in answering a range of questions in ecology and conservation biology. To our knowledge, this is the largest and most geographically and taxonomically representative database of spatial comparisons of biodiversity that has been collated to date; it will be useful to researchers and international efforts wishing to model and understand the global status of biodiversity.
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| 3. |
- Plomion, Christophe, et al.
(författare)
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Oak genome reveals facets of long lifespan
- 2018
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Ingår i: NATURE PLANTS. - : Springer Science and Business Media LLC. - 2055-026X .- 2055-0278. ; 4:7, s. 440-452
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Tidskriftsartikel (refereegranskat)abstract
- Oaks are an important part of our natural and cultural heritage. Not only are they ubiquitous in our most common landscapes' but they have also supplied human societies with invaluable services, including food and shelter, since prehistoric times(2). With 450 species spread throughout Asia, Europe and America(3), oaks constitute a critical global renewable resource. The longevity of oaks (several hundred years) probably underlies their emblematic cultural and historical importance. Such long-lived sessile organisms must persist in the face of a wide range of abiotic and biotic threats over their lifespans. We investigated the genomic features associated with such a long lifespan by sequencing, assembling and annotating the oak genome. We then used the growing number of whole-genome sequences for plants (including tree and herbaceous species) to investigate the parallel evolution of genomic characteristics potentially underpinning tree longevity. A further consequence of the long lifespan of trees is their accumulation of somatic mutations during mitotic divisions of stem cells present in the shoot apical meristems. Empirical(4) and modelling(5) approaches have shown that intra-organismal genetic heterogeneity can be selected for(6) and provides direct fitness benefits in the arms race with short-lived pests and pathogens through a patchwork of intra-organismal phenotypes(7). However, there is no clear proof that large-statured trees consist of a genetic mosaic of clonally distinct cell lineages within and between branches. Through this case study of oak, we demonstrate the accumulation and transmission of somatic mutations and the expansion of disease-resistance gene families in trees.
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| 4. |
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| 5. |
- Lawrenson, Kate, et al.
(författare)
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Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10-20), ER-negative BC (P=1.1 × 10-13), BRCA1-associated BC (P=7.7 × 10-16) and triple negative BC (P-diff=2 × 10-5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10-3) and ABHD8 (P<2 × 10-3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3′-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk.
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| 6. |
- Mewton, Nathan, et al.
(författare)
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Rationale and design of the Cyclosporine to ImpRove Clinical oUtcome in ST-elevation myocardial infarction patients (the CIRCUS trial)
- 2015
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Ingår i: American Heart Journal. - : Elsevier BV. - 1097-6744 .- 0002-8703. ; 169:6, s. 6-766
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Tidskriftsartikel (refereegranskat)abstract
- Background Both acute myocardial ischemia and reperfusion contribute to cardiomyocyte death in ST-elevation myocardial infarction (STEMI). The final infarct size is the principal determinant of subsequent clinical outcome in STEMI patients. In a proof-of-concept phase II trial, the administration of cyclosporine prior to primary percutaneous coronary intervention (PPCI) has been associated with a reduction of infarct size in STEMI patients. Methods CIRCUS is an international, prospective, multicenter, randomized, double-blinded, placebo-controlled trial. The study is designed to compare the efficacy and safety of cyclosporine versus placebo, in addition to revascularization by PPCI, in patients presenting with acute anterior myocardial infarction within 12 hours of symptoms onset and initial TIMI flow <= 1 in the culprit left anterior descending coronary artery. Patients are randomized in a 1: 1 fashion to 2.5 mg/kg intravenous infusion of cyclosporine or matching placebo performed in theminutes preceding PCI. The primary efficacy end point of CIRCUS is a composite of 1-year all-cause mortality, rehospitalization for heart failure or heart failure worsening during initial hospitalization, and left ventricular adverse remodeling as determined by sequential transthoracic echochardiography. Secondary outcomes will be tested using a hierarchical sequence of left ventricular (LV) ejection fraction and absolute measurements of LV volumes. The composite of death and rehospitalization for heart failure or heart failure worsening during initial hospitalization will be further assessed at three years after the initial infarction. Results Recruitment lasted from April 2011 to February 2014. The CIRCUS trial has recruited 975 patients with acute anterior myocardial infarction. The 12-months results are expected to be available in 2015. Conclusions The CIRCUS trial is testing the hypothesis that cyclosporine in addition to early revascularization with PPCI compared to placebo in patients with acute anterior myocardial infarction reduces the incidence of death, heart failure and adverse LV remodeling at one-year follow-up.
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| 7. |
- Pandolfi, Marco, et al.
(författare)
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A European aerosol phenomenology-6 : scattering properties of atmospheric aerosol particles from 28 ACTRIS sites
- 2018
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Ingår i: Atmospheric Chemistry And Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 18:11, s. 7877-7911
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Tidskriftsartikel (refereegranskat)abstract
- This paper presents the light-scattering properties of atmospheric aerosol particles measured over the past decade at 28 ACTRIS observatories, which are located mainly in Europe. The data include particle light scattering (sigma(sp)) and hemispheric backscattering (sigma(bsp)) coefficients, scattering Angstrom exponent (SAE), backscatter fraction (BF) and asymmetry parameter (g). An increasing gradient of sigma(sp) is observed when moving from remote environments (arctic/mountain) to regional and to urban environments. At a regional level in Europe, sigma(sp) also increases when moving from Nordic and Baltic countries and from western Europe to central/eastern Europe, whereas no clear spatial gradient is observed for other station environments. The SAE does not show a clear gradient as a function of the placement of the station. However, a west-to-east-increasing gradient is observed for both regional and mountain placements, suggesting a lower fraction of fine-mode particle in western/south-western Europe compared to central and eastern Europe, where the fine-mode particles dominate the scattering. The g does not show any clear gradient by station placement or geographical location reflecting the complex relationship of this parameter with the physical properties of the aerosol particles. Both the station placement and the geographical location are important factors affecting the intraannual variability. At mountain sites, higher sigma(sp) and SAE values are measured in the summer due to the enhanced boundary layer influence and/or new particle-formation episodes. Conversely, the lower horizontal and vertical dispersion during winter leads to higher sigma(sp) values at all low-altitude sites in central and eastern Europe compared to summer. These sites also show SAE maxima in the summer (with corresponding g minima). At all sites, both SAE and g show a strong variation with aerosol particle loading. The lowest values of g are always observed together with low sigma(sp) values, indicating a larger contribution from particles in the smaller accumulation mode. During periods of high sigma(sp) values, the variation of g is less pronounced, whereas the SAE increases or decreases, suggesting changes mostly in the coarse aerosol particle mode rather than in the fine mode. Statistically significant decreasing trends of sigma(sp) are observed at 5 out of the 13 stations included in the trend analyses. The total reductions of sigma(sp) are consistent with those reported for PM2.5 and PM10 mass concentrations over similar periods across Europe.
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| 8. |
- Rotundi, Alessandra, et al.
(författare)
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Dust measurements in the coma of comet 67P/Churyumov-Gerasimenko inbound to the Sun
- 2015
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 347:6220
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Tidskriftsartikel (refereegranskat)abstract
- Critical measurements for understanding accretion and the dust/gas ratio in the solar nebula, where planets were forming 4.5 billion years ago, are being obtained by the GIADA (Grain Impact Analyser and Dust Accumulator) experiment on the European Space Agency's Rosetta spacecraft orbiting comet 67P/Churyumov-Gerasimenko. Between 3.6 and 3.4 astronomical units inbound, GIADA and OSIRIS (Optical, Spectroscopic, and Infrared Remote Imaging System) detected 35 outflowing grains of mass 10(-10) to 10(-7) kilograms, and 48 grains of mass 10(-5) to 10(-2) kilograms, respectively. Combined with gas data from the MIRO (Microwave Instrument for the Rosetta Orbiter) and ROSINA (Rosetta Orbiter Spectrometer for Ion and Neutral Analysis) instruments, we find a dust/gas mass ratio of 4 +/- 2 averaged over the sunlit nucleus surface. A cloud of larger grains also encircles the nucleus in bound orbits from the previous perihelion. The largest orbiting clumps are meter-sized, confirming the dust/gas ratio of 3 inferred at perihelion from models of dust comae and trails.
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| 9. |
- Zamora, Juan Carlos, et al.
(författare)
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Considerations and consequences of allowing DNA sequence data as types of fungal taxa
- 2018
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Ingår i: IMA Fungus. - : INT MYCOLOGICAL ASSOC. - 2210-6340 .- 2210-6359. ; 9:1, s. 167-185
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Tidskriftsartikel (refereegranskat)abstract
- Nomenclatural type definitions are one of the most important concepts in biological nomenclature. Being physical objects that can be re-studied by other researchers, types permanently link taxonomy (an artificial agreement to classify biological diversity) with nomenclature (an artificial agreement to name biological diversity). Two proposals to amend the International Code of Nomenclature for algae, fungi, and plants (ICN), allowing DNA sequences alone (of any region and extent) to serve as types of taxon names for voucherless fungi (mainly putative taxa from environmental DNA sequences), have been submitted to be voted on at the 11th International Mycological Congress (Puerto Rico, July 2018). We consider various genetic processes affecting the distribution of alleles among taxa and find that alleles may not consistently and uniquely represent the species within which they are contained. Should the proposals be accepted, the meaning of nomenclatural types would change in a fundamental way from physical objects as sources of data to the data themselves. Such changes are conducive to irreproducible science, the potential typification on artefactual data, and massive creation of names with low information content, ultimately causing nomenclatural instability and unnecessary work for future researchers that would stall future explorations of fungal diversity. We conclude that the acceptance of DNA sequences alone as types of names of taxa, under the terms used in the current proposals, is unnecessary and would not solve the problem of naming putative taxa known only from DNA sequences in a scientifically defensible way. As an alternative, we highlight the use of formulas for naming putative taxa (candidate taxa) that do not require any modification of the ICN.
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| 10. |
- Akiyama, Kazunori, et al.
(författare)
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First M87 Event Horizon Telescope Results. IV. Imaging the Central Supermassive Black Hole
- 2019
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Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 875:1
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Tidskriftsartikel (refereegranskat)abstract
- We present the first Event Horizon Telescope (EHT) images of M87, using observations from April 2017 at 1.3 mm wavelength. These images show a prominent ring with a diameter of similar to 40 mu as, consistent with the size and shape of the lensed photon orbit encircling the "shadow" of a supermassive black hole. The ring is persistent across four observing nights and shows enhanced brightness in the south. To assess the reliability of these results, we implemented a two-stage imaging procedure. In the first stage, four teams, each blind to the others' work, produced images of M87 using both an established method (CLEAN) and a newer technique (regularized maximum likelihood). This stage allowed us to avoid shared human bias and to assess common features among independent reconstructions. In the second stage, we reconstructed synthetic data from a large survey of imaging parameters and then compared the results with the corresponding ground truth images. This stage allowed us to select parameters objectively to use when reconstructing images of M87. Across all tests in both stages, the ring diameter and asymmetry remained stable, insensitive to the choice of imaging technique. We describe the EHT imaging procedures, the primary image features in M87, and the dependence of these features on imaging assumptions.
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| 11. |
- Akiyama, Kazunori, et al.
(författare)
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First M87 Event Horizon Telescope Results. V. Physical Origin of the Asymmetric Ring
- 2019
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Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 875:1
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Tidskriftsartikel (refereegranskat)abstract
- The Event Horizon Telescope (EHT) has mapped the central compact radio source of the elliptical galaxy M87 at 1.3 mm with unprecedented angular resolution. Here we consider the physical implications of the asymmetric ring seen in the 2017 EHT data. To this end, we construct a large library of models based on general relativistic magnetohydrodynamic (GRMHD) simulations and synthetic images produced by general relativistic ray tracing. We compare the observed visibilities with this library and confirm that the asymmetric ring is consistent with earlier predictions of strong gravitational lensing of synchrotron emission from a hot plasma orbiting near the black hole event horizon. The ring radius and ring asymmetry depend on black hole mass and spin, respectively, and both are therefore expected to be stable when observed in future EHT campaigns. Overall, the observed image is consistent with expectations for the shadow of a spinning Kerr black hole as predicted by general relativity. If the black hole spin and M87's large scale jet are aligned, then the black hole spin vector is pointed away from Earth. Models in our library of non-spinning black holes are inconsistent with the observations as they do not produce sufficiently powerful jets. At the same time, in those models that produce a sufficiently powerful jet, the latter is powered by extraction of black hole spin energy through mechanisms akin to the Blandford-Znajek process. We briefly consider alternatives to a black hole for the central compact object. Analysis of existing EHT polarization data and data taken simultaneously at other wavelengths will soon enable new tests of the GRMHD models, as will future EHT campaigns at 230 and 345 GHz.
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| 12. |
- Akiyama, Kazunori, et al.
(författare)
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First M87 Event Horizon Telescope Results. VI. The Shadow and Mass of the Central Black Hole
- 2019
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Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 875:1
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Tidskriftsartikel (refereegranskat)abstract
- We present measurements of the properties of the central radio source in M87 using Event Horizon Telescope data obtained during the 2017 campaign. We develop and fit geometric crescent models (asymmetric rings with interior brightness depressions) using two independent sampling algorithms that consider distinct representations of the visibility data. We show that the crescent family of models is statistically preferred over other comparably complex geometric models that we explore. We calibrate the geometric model parameters using general relativistic magnetohydrodynamic (GRMHD) models of the emission region and estimate physical properties of the source. We further fit images generated from GRMHD models directly to the data. We compare the derived emission region and black hole parameters from these analyses with those recovered from reconstructed images. There is a remarkable consistency among all methods and data sets. We find that >50% of the total flux at arcsecond scales comes from near the horizon, and that the emission is dramatically suppressed interior to this region by a factor >10, providing direct evidence of the predicted shadow of a black hole. Across all methods, we measure a crescent diameter of 42 +/- 3 mu as and constrain its fractional width to be
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| 13. |
- Alkerwi, Ala'a, et al.
(författare)
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Adherence to physical activity recommendations and its associated factors: an interregional population-based study.
- 2015
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Ingår i: Journal of Public Health Research. - : SAGE Publications. - 2279-9028 .- 2279-9036. ; 4:1, s. 406-406
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Tidskriftsartikel (refereegranskat)abstract
- Though the influence of physical activity in preventing cardiovascular diseases is well documented, only a few comparative studies have determined the degree of adherence to physical activity recommendations among populations and identified the demographic, socioeco-nomic, behavioural and health-related factors associated with good compliance.
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| 14. |
- Arndt, D. S., et al.
(författare)
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STATE OF THE CLIMATE IN 2017
- 2018
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Ingår i: Bulletin of The American Meteorological Society - (BAMS). - : American Meteorological Society. - 0003-0007 .- 1520-0477. ; 99:8, s. S1-S310
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Forskningsöversikt (refereegranskat)
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| 15. |
- Barra, Sérgio, et al.
(författare)
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Very long-term survival and late sudden cardiac death in cardiac resynchronization therapy patients
- 2019
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 1522-9645 .- 0195-668X. ; 40:26, s. 2121-2127
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: The very long-term outcome of patients who survive the first few years after receiving cardiac resynchronization therapy (CRT) has not been well described thus far. We aimed to provide long-term outcomes, especially with regard to the occurrence of sudden cardiac death (SCD), in CRT patients without (CRT-P) and with defibrillator (CRT-D).METHODS AND RESULTS: A total of 1775 patients, with ischaemic or non-ischaemic dilated cardiomyopathy, who were alive 5 years after CRT implantation, were enrolled in this multicentre European observational cohort study. Overall long-term mortality rates and specific causes of death were assessed, with a focus on late SCD. Over a mean follow-up of 30 months (interquartile range 10-42 months) beyond the first 5 years, we observed 473 deaths. The annual age-standardized mortality rates of CRT-D and CRT-P patients were 40.4 [95% confidence interval (CI) 35.3-45.5] and 97.2 (95% CI 85.5-109.9) per 1000 patient-years, respectively. The adjusted hazard ratio (HR) for all-cause mortality was 0.99 (95% CI 0.79-1.22). Twenty-nine patients in total died of late SCD (14 with CRT-P, 15 with CRT-D), corresponding to 6.1% of all causes of death in both device groups. Specific annual SCD rates were 8.5 and 5.8 per 1000 patient-years in CRT-P and CRT-D patients, respectively, with no significant difference between groups (adjusted HR 1.0, 95% CI 0.45-2.44). Death due to progressive heart failure represented the principal cause of death (42.8% in CRT-P patients and 52.6% among CRT-D recipients), whereas approximately one-third of deaths in both device groups were due to non-cardiovascular death.CONCLUSION: In this first description of very long-term outcomes among CRT recipients, progressive heart failure death still represented the most frequent cause of death in patients surviving the first 5 years after CRT implant. In contrast, SCD represents a very low proportion of late mortality irrespective of the presence of a defibrillator.
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| 16. |
- Bousquet, J. Jean, et al.
(författare)
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Next-generation ARIA care pathways for rhinitis and asthma : a model for multimorbid chronic diseases
- 2019
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Ingår i: Clinical and Translational Allergy. - : BMC. - 2045-7022. ; 9
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Forskningsöversikt (refereegranskat)abstract
- Background: In all societies, the burden and cost of allergic and chronic respiratory diseases are increasing rapidly. Most economies are struggling to deliver modern health care effectively. There is a need to support the transformation of the health care system into integrated care with organizational health literacy.Main body: As an example for chronic disease care, MASK (Mobile Airways Sentinel NetworK), a new project of the ARIA (Allergic Rhinitis and its Impact on Asthma) initiative, and POLLAR (Impact of Air POLLution on Asthma and Rhinitis, EIT Health), in collaboration with professional and patient organizations in the field of allergy and airway diseases, are proposing real-life ICPs centred around the patient with rhinitis, and using mHealth to monitor environmental exposure. Three aspects of care pathways are being developed: (i) Patient participation, health literacy and self-care through technology-assisted "patient activation", (ii) Implementation of care pathways by pharmacists and (iii) Next-generation guidelines assessing the recommendations of GRADE guidelines in rhinitis and asthma using real-world evidence (RWE) obtained through mobile technology. The EU and global political agendas are of great importance in supporting the digital transformation of health and care, and MASK has been recognized by DG Sante as a Good Practice in the field of digitally-enabled, integrated, person-centred care.Conclusion: In 20 years, ARIA has considerably evolved from the first multimorbidity guideline in respiratory diseases to the digital transformation of health and care with a strong political involvement.
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| 17. |
- Callac, Nolwenn, et al.
(författare)
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Pyrococcus kukulkanii sp nov., a hyperthermophilic, piezophilic archaeon isolated from a deep-sea hydrothermal vent
- 2016
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Ingår i: International Journal of Systematic and Evolutionary Microbiology. - : Microbiology Society. - 1466-5026 .- 1466-5034. ; 66, s. 3142-3149
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Tidskriftsartikel (refereegranskat)abstract
- A novel hyperthermophilic, piezophilic, anaerobic archaeon, designated NCB100(T), was isolated from a hydrothermal vent flange fragment collected in the Guaymas basin at the hydrothermal vent site named 'Rebecca's Roost' at a depth of 1997 m. Enrichment and isolation were performed at 100 degrees C under atmospheric pressure. Cells of strain NCB100(T) were highly motile, irregular cocci with a diameter of -1 mu m. Growth was recorded at temperatures between 70 and 112 degrees C (optimum 105 degrees C) and hydrostatic pressures of 0.1-80 MPa (optimum 40-50 MPa). Growth was observed at pH 3.5-8.5 (optimum pH 7) and with 1.5-7% NaCl (optimum at 2.5-3 %). Strain NCB100(T) was a strictly anaerobic chemo-organoheterotroph and grew on complex proteinaceous substrates such as yeast extract, peptone and tryptone, as well as on glycogen and starch. Elemental sulfur was required for growth and was reduced to hydrogen sulfide. The fermentation products from complex proteinaceous substrates were CO2 and H-2. The G+C content of the genomic DNA was 41.3 %. Phylogenetic analysis of the 16S rRNA gene sequence revealed that strain NCB100(T) belongs to the genus Pyrococcus, showing 99% similarity with the other described species of the genus Pyrococcus. On the basis of physiological characteristics, DNA G+C content, similarity level between ribosomal proteins and an average nucleotide identity value of 79 %, strain NCB100(T) represents a novel species for which the name Pyrococcus kukulkanii sp. nov. is proposed. The type strain is NCB100(T) (=DSM 101590(T) =Souchotheque de Bretagne BG1337(T)).
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| 18. |
- Carde, Patrice, et al.
(författare)
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Eight Cycles of ABVD Versus Four Cycles of BEACOPP(escalated) Plus Four Cycles of BEACOPP(baseline) in Stage III to IV, International Prognostic Score >= 3, High-Risk Hodgkin Lymphoma : First Results of the Phase III EORTC 20012 Intergroup Trial
- 2016
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Ingår i: Journal of Clinical Oncology. - 0732-183X .- 1527-7755. ; 34:17, s. 2028-
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Tidskriftsartikel (refereegranskat)abstract
- Purpose To compare patients with high-risk stage III to IV Hodgkin lymphoma (HL) in the phase III European Organisation for Research and Treatment of Cancer 20012 Intergroup trial (Comparison of Two Combination Chemotherapy Regimens in Treating Patients With Stage III or Stage IV Hodgkin's Lymphoma) who were randomly assigned to either doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) or to bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP). Patients and Methods Patients with clinical stage III or IV HL, International Prognostic Score of 3 or higher, and age 60 years or younger received ABVD for eight cycles (ABVD(8)) or escalated-dose BEACOPP (BEACOPP(escalated)) for four cycles followed by baseline BEACOPP (BEACOPP(baseline)) for four cycles (BEACOPP(4+4)) without radiotherapy. Primary end points were event-free survival (EFS), treatment discontinuation, no complete response (CR) or unconfirmed complete response (CRu) after eight cycles, progression, relapse, or death. Secondary end points were CR rate, overall survival (OS), quality of life, secondary malignancies, and disease-free survival in CR/CRu patients. Results Between 2002 and 2010, 549 patients were randomly assigned to ABVD(8) (n = 275) or BEACOPP(4+4) (n = 274). Other characteristics included median age, 35 years; male, 75%; stage IV, 74%; "B" symptoms, 81%; and International Prognostic Score >= 4, 59%. WHO performance status was 0 (34%), 1 (48%), or 2 (17%). Median follow-upwas 3.6 years. CR/CRu was 82.5% in both arms. At 4 years, EFS was 63.7% for ABVD(8) versus 69.3% for BEACOPP(4+4) (hazard ratio [HR], 0.86; 95% CI, 0.64 to 1.15; P = .312); disease-free survival was 85.8% versus 91.0% (HR, 0.59; 95% CI, 0.33 to 1.06; P = .076), and OS was 86.7% versus 90.3% (HR, 0.71; 95% CI, 0.42 to 1.21; P = .208). Death as a result of toxicity occurred in six and five patients, early discontinuation (before cycle 5) in 12 and 26 patients, treatment crossovers in five and 10 patients, and secondary malignancies in eight and 10 patients in the ABVD(8) and BEACOPP(4+4) arms, respectively. Conclusion ABVD(8) and BEACOPP(4+4) resulted in similar EFS and OS in patients with high-risk advanced-stage HL. Because BEACOPP(4+4) did not demonstrate a favorable effectiveness or toxicity ratio compared with ABVD(8), treatment burden, immediate and late toxicities, and associated costs must be considered before selecting one of these regimens on which to build future treatment strategies.
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| 19. |
- Chrobok, Daria, et al.
(författare)
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Dissecting the Metabolic Role of Mitochondria during Developmental Leaf Senescence
- 2016
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Ingår i: Plant Physiology. - : Oxford University Press (OUP). - 0032-0889 .- 1532-2548. ; 172:4, s. 2132-2153
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Tidskriftsartikel (refereegranskat)abstract
- The functions of mitochondria during leaf senescence, a type of programmed cell death aimed at the massive retrieval of nutrients from the senescing organ to the rest of the plant, remain elusive. Here, combining experimental and analytical approaches, we showed that mitochondrial integrity in Arabidopsis (Arabidopsis thaliana) is conserved until the latest stages of leaf senescence, while their number drops by 30%. Adenylate phosphorylation state assays and mitochondrial respiratory measurements indicated that the leaf energy status also is maintained during this time period. Furthermore, after establishing a curated list of genes coding for products targeted to mitochondria, we analyzed in isolation their transcript profiles, focusing on several key mitochondrial functions, such as the tricarboxylic acid cycle, mitochondrial electron transfer chain, iron-sulfur cluster biosynthesis, transporters, as well as catabolic pathways. In tandem with a metabolomic approach, our data indicated that mitochondrial metabolism was reorganized to support the selective catabolism of both amino acids and fatty acids. Such adjustments would ensure the replenishment of alpha-ketoglutarate and glutamate, which provide the carbon backbones for nitrogen remobilization. Glutamate, being the substrate of the strongly up-regulated cytosolic glutamine synthase, is likely to become a metabolically limiting factor in the latest stages of developmental leaf senescence. Finally, an evolutionary age analysis revealed that, while branched-chain amino acid and proline catabolism are very old mitochondrial functions particularly enriched at the latest stages of leaf senescence, auxin metabolism appears to be rather newly acquired. In summation, our work shows that, during developmental leaf senescence, mitochondria orchestrate catabolic processes by becoming increasingly central energy and metabolic hubs.
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| 20. |
- Darwich, Adam S., et al.
(författare)
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IMI - Oral biopharmaceutics tools project - Evaluation of bottom-up PBPK prediction success part 3 : Identifying gaps in system parameters by analysing In Silico performance across different compound classes
- 2017
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Ingår i: European Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0928-0987 .- 1879-0720. ; 96, s. 626-642
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Tidskriftsartikel (refereegranskat)abstract
- Three Physiologically Based Pharmacokinetic software packages (GI-Sim, Simcyp (R) Simulator, and GastroPlus (TM)) were evaluated as part of the Innovative Medicine Initiative Oral Biopharmaceutics Tools project (OrBiTo) during a blinded "bottom-up" anticipation of human pharmacokinetics. After data analysis of the predicted vs. measured pharmacokinetics parameters, it was found that oral bioavailability (F-oral) was underpredicted for compounds with low permeability, suggesting improper estimates of intestinal surface area, colonic absorption and/or lack of intestinal transporter information. Foralwas also underpredicted for acidic compounds, suggesting overestimation of impact of ionisation on permeation, lack of information on intestinal transporters, or underestimation of solubilisation of weak acids due to less than optimal intestinal model pH settings or underestimation of bile micelle contribution. F-oral was overpredicted for weak bases, suggesting inadequate models for precipitation or lack of in vitro precipitation information to build informed models. Relative bioavailability was underpredicted for both high logP compounds as well as poorly water-soluble compounds, suggesting inadequate models for solubility/dissolution, underperforming bile enhancement models and/or lack of biorelevant solubility measurements. These results indicate areas for improvement in model software, modelling approaches, and generation of applicable input data. However, caution is required when interpreting the impact of drug-specific properties in this exercise, as the availability of input parameters was heterogeneous and highly variable, and the modellers generally used the data "as is" in this blinded bottom-up prediction approach.
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| 21. |
- Dittrich, Christian, et al.
(författare)
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ESMO / ASCO Recommendations for a Global Curriculum in Medical Oncology Edition 2016
- 2016
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Ingår i: ESMO Open. - : Elsevier BV. - 2059-7029. ; 1:5
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Tidskriftsartikel (refereegranskat)abstract
- The European Society for Medical Oncology (ESMO) and the American Society of Clinical Oncology (ASCO) are publishing a new edition of the ESMO/ ASCO Global Curriculum (GC) thanks to contribution of 64 ESMOappointed and 32 ASCO-appointed authors. First published in 2004 and updated in 2010, the GC edition 2016 answers to the need for updated recommendations for the training of physicians in medical oncology by defining the standard to be fulfilled to qualify as medical oncologists. At times of internationalisation of healthcare and increased mobility of patients and physicians, the GC aims to provide state-of-the-art cancer care to all patients wherever they live. Recent progress in the field of cancer research has indeed resulted in diagnostic and therapeutic innovations such as targeted therapies as a standard therapeutic approach or personalised cancer medicine specialised training for medical oncology trainees. Thus, several new chapters on technical contents such as molecular pathology, translational research or molecular imaging and on conceptual attitudes towards human principles like genetic counselling or survivorship have been integrated in the GC. The GC edition 2016 consists of 12 sections with 17 subsections, 44 chapters and 35 subchapters, respectively. Besides renewal in its contents, the GC underwent a principal formal change taking into consideration modern didactic principles. It is presented in a template-based format that subcategorises the detailed outcome requirements into learning objectives, awareness, knowledge and skills. Consecutive steps will be those of harmonising and implementing teaching and assessment strategies.
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| 22. |
- Gueriau, Pierre, et al.
(författare)
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A 365-Million-Year-Old Freshwater Community Reveals Morphological and Ecological Stasis in Branchiopod Crustaceans
- 2016
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Ingår i: Current Biology. - : Elsevier BV. - 0960-9822 .- 1879-0445. ; 26:3, s. 383-390
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Tidskriftsartikel (refereegranskat)abstract
- Branchiopod crustaceans are represented by fairy, tadpole, and clam shrimps (Anostraca, Notostraca, Laevicaudata, Spinicaudata), which typically inhabit temporary freshwater bodies, and water fleas (Cladoceromorpha), which live in all kinds of freshwater and occasionally marine environments [1, 2]. The earliest branchiopods occur in the Cambrian, where they are represented by complete body fossils from Sweden such as Rehbachiella kinnekullensis [3] and isolated mandibles preserved as small carbonaceous fossils [4-6] from Canada. The earliest known continental branchiopods are associated with hot spring environments [7] represented by the Early Devonian Rhynie Chert of Scotland (410 million years ago) and include possible stem-group or crown-group Anostraca, Notostraca, and clam shrimps or Cladoceromorpha [8-10], which differmorphologically fromtheirmodern counterparts [1, 2, 11]. Here we report the discovery of an ephemeral pool branchiopod community from the 365-million-year-old Strud locality of Belgium. It is characterized by new anostracans and spinicaudatans, closely resembling extant species, and the earliest notostracan, Strudops goldenbergi [12]. These branchiopods released resting eggs into the sediment in a manner similar to their modern representatives [1, 2]. We infer that this reproductive strategy was critical to overcoming environmental constraints such as seasonal desiccation imposed by living on land. The pioneer colonization of ephemeral freshwater pools by branchiopods in the Devonian was followed by remarkable ecological and morphological stasis that persists to the present day.
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| 23. |
- Johansson, Mattias, et al.
(författare)
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The influence of obesity-related factors in the etiology of renal cell carcinoma—A mendelian randomization study
- 2019
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Ingår i: PLoS Medicine. - : Public Library of Science (PLoS). - 1549-1277 .- 1549-1676. ; 16:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Several obesity-related factors have been associated with renal cell carcinoma (RCC), but it is unclear which individual factors directly influence risk. We addressed this question using genetic markers as proxies for putative risk factors and evaluated their relation to RCC risk in a mendelian randomization (MR) framework. This methodology limits bias due to confounding and is not affected by reverse causation.Methods and findings: Genetic markers associated with obesity measures, blood pressure, lipids, type 2 diabetes, insulin, and glucose were initially identified as instrumental variables, and their association with RCC risk was subsequently evaluated in a genome-wide association study (GWAS) of 10,784 RCC patients and 20,406 control participants in a 2-sample MR framework. The effect on RCC risk was estimated by calculating odds ratios (ORSD) for a standard deviation (SD) increment in each risk factor. The MR analysis indicated that higher body mass index increases the risk of RCC (ORSD: 1.56, 95% confidence interval [CI] 1.44–1.70), with comparable results for waist-to-hip ratio (ORSD: 1.63, 95% CI 1.40–1.90) and body fat percentage (ORSD: 1.66, 95% CI 1.44–1.90). This analysis further indicated that higher fasting insulin (ORSD: 1.82, 95% CI 1.30–2.55) and diastolic blood pressure (DBP; ORSD: 1.28, 95% CI 1.11–1.47), but not systolic blood pressure (ORSD: 0.98, 95% CI 0.84–1.14), increase the risk for RCC. No association with RCC risk was seen for lipids, overall type 2 diabetes, or fasting glucose.Conclusions: This study provides novel evidence for an etiological role of insulin in RCC, as well as confirmatory evidence that obesity and DBP influence RCC risk.
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| 24. |
- Keech, Olivier, et al.
(författare)
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The redox control of photorespiration : from biochemical and physiological aspects to biotechnological considerations
- 2017
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Ingår i: Plant, Cell and Environment. - : Wiley. - 0140-7791 .- 1365-3040. ; 40:4, s. 553-569
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Forskningsöversikt (refereegranskat)abstract
- Photorespiration is a complex and tightly regulated process occurring in photosynthetic organisms. This process can alter the cellular redox balance, notably via the production and consumption of both reducing and oxidizing equivalents. Under certain circumstances, these equivalents, as well as reactive oxygen or nitrogen species, can become prominent in subcellular compartments involved in the photorespiratory process, eventually promoting oxidative post-translational modifications of proteins. Keeping these changes under tight control should therefore be of primary importance. In order to review the current state of knowledge about the redox control of photorespiration, we primarily performed a careful description of the known and potential redox-regulated or oxidation sensitive photorespiratory proteins, and examined in more details two interesting cases: the glycerate kinase and the glycine cleavage system. When possible, the potential impact and subsequent physiological regulations associated with these changes have been discussed. In a second part, we reviewed the extent to which photorespiration contributes to cellular redox homeostasis considering, in particular, the set of peripheral enzymes associated with the canonical photorespiratory pathway. Finally, some recent biotechnological strategies to circumvent photorespiration for future growth improvements are discussed in the light of these redox regulations.
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| 25. |
- Kirsebom, O. S., et al.
(författare)
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First Accurate Normalization of the β -delayed α Decay of N 16 and Implications for the C 12 (α,γ) O 16 Astrophysical Reaction Rate
- 2018
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Ingår i: Physical Review Letters. - 1079-7114 .- 0031-9007. ; 121:14
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Tidskriftsartikel (refereegranskat)abstract
- Published by the American Physical Society. The C12(α,γ)O16 reaction plays a central role in astrophysics, but its cross section at energies relevant for astrophysical applications is only poorly constrained by laboratory data. The reduced α width, γ11, of the bound 1- level in O16 is particularly important to determine the cross section. The magnitude of γ11 is determined via sub-Coulomb α-transfer reactions or the β-delayed α decay of N16, but the latter approach is presently hampered by the lack of sufficiently precise data on the β-decay branching ratios. Here we report improved branching ratios for the bound 1- level [bβ,11=(5.02±0.10)×10-2] and for β-delayed α emission [bβα=(1.59±0.06)×10-5]. Our value for bβα is 33% larger than previously held, leading to a substantial increase in γ11. Our revised value for γ11 is in good agreement with the value obtained in α-transfer studies and the weighted average of the two gives a robust and precise determination of γ11, which provides significantly improved constraints on the C12(α,γ) cross section in the energy range relevant to hydrostatic He burning.
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| 26. |
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| 27. |
- Lai, Ian-Lin, et al.
(författare)
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Gas outflow and dust transport of comet 67P/Churyumov-Gerasimenko
- 2016
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Ingår i: Monthly notices of the Royal Astronomical Society. - : OXFORD UNIV PRESS. - 0035-8711 .- 1365-2966. ; 462, s. S533-S546
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Tidskriftsartikel (refereegranskat)abstract
- Because of the diurnal thermal cycle and the irregular shape of the nucleus, gas outflow of comet 67P/Churyumov-Gerasimenko could be highly anisotropic as indicated by the colliminated dust jet structures on the sunlit side. Based on the OSIRIS imaging observations of the outgassing effect, a simple model of surface sublimation can be constructed by taking into account the dependence on the solar insolation. With preliminary information on the time variability of the global gas production rate, a sequence of gas coma models can be generated at different epochs before and after perihelion. We also investigate different patterns of dust particle dynamics under the influences of nuclear rotation and gas drag. From these considerations, a consistent picture of the spatial distribution of dusty materials across the surface of comet 67P as it moves around the perihelion can be developed. It is found that because of the redeposition of the ejected dust from the Southern hemisphere to the Northern hemisphere during the southern summer season the Hapi region could gain up to 0.4 m while the Wosret region would lose up to 1.8 m of dust mantle per orbit.
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| 28. |
- Law, Simon R., et al.
(författare)
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Darkened leaves use different metabolic strategies for senescence and survival
- 2018
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Ingår i: Plant Physiology. - : Oxford University Press (OUP). - 0032-0889 .- 1532-2548. ; 177:1, s. 132-150
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Tidskriftsartikel (refereegranskat)abstract
- In plants, an individually darkened leaf initiates senescence much more rapidly than a leaf from a whole darkened plant. Combining transcriptomic and metabolomic approaches in Arabidopsis (Arabidopsis thaliana), we present an overview of the metabolic strategies that are employed in response to different darkening treatments. Under darkened plant conditions, the perception of carbon starvation drove a profound metabolic readjustment in which branched-chain amino acids and potentially monosaccharides released from cell wall loosening became important substrates for maintaining minimal ATP production. Concomitantly, the increased accumulation of amino acids with a high nitrogen-carbon ratio may provide a safety mechanism for the storage of metabolically derived cytotoxic ammonium and a pool of nitrogen for use upon returning to typical growth conditions. Conversely, in individually darkened leaf, the metabolic profiling that followed our 13C-enrichment assays revealed a temporal and differential exchange of metabolites, including sugars and amino acids, between the darkened leaf and the rest of the plant. This active transport could be the basis for a progressive metabolic shift in the substrates fueling mitochondrial activities, which are central to the catabolic reactions facilitating the retrieval of nutrients from the senescing leaf. We propose a model illustrating the specific metabolic strategies employed by leaves in response to these two darkening treatments, which support either rapid senescence or a strong capacity for survival.
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| 29. |
- Lee, Jui-Chi, et al.
(författare)
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Geomorphological mapping of comet 67P/Churyumov-Gerasimenko's Southern hemisphere
- 2016
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 462, s. S573-S592
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Tidskriftsartikel (refereegranskat)abstract
- In 2015 May, the Southern hemisphere of comet 67P/Churyumov-Gerasimenko became visible by the OSIRIS cameras on-board the Rosetta spacecraft. The resolution was high enough to carry out a detailed analysis of the surface morphology, which is quite different from the Northern hemisphere. Previous works show that fine particle deposits are the most extensive geological unit in the Northern hemisphere. In contrast, the Southern hemisphere is dominated by outcropping consolidated terrain. In this work, we provide geomorphological maps of the Southern hemisphere with the distinction of both geological units and linear features. The geomorphological maps described in this study allow us to gain a better understanding of the processes shaping the comet nucleus and the distribution of primary structures such as fractures and strata.
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| 30. |
- Liebsch, Daniela, et al.
(författare)
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Metabolic adjustments required for extended leaf longevity under prolonged darkness revealed by a new loss of function allele of PIF5
- 2018
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Senescence is regulated by a complex interplay of factors and regulatory circuits, which may be accelerated or delayed depending on the integrated signals. Using a forward genetic screen in Arabidopsis thaliana, we identified a mutant strongly delayed in its induction of senescence in response to prolonged darkness. This mutant, which corresponds to a novel loss-of-function allele of PIF5 (PHYTOCHROME-INTERACTING FACTOR 5), exhibits even slightly more extended survival of leaves in darkness than the previously reported pif5-3 TDNA knock-out line. In the present study, we additionally aimed at deciphering the metabolic and regulatory processes conferring this enhanced capacity for survival in pif5 mutants. We combined physiological, metabolomic and transcriptomic analyses, and discovered that the extended survival of mutant leaves in darkness was associated with reduced protein degradation, slight differences in amino acid catabolism related gene expression as well as strong reduction of amino acid transporter expression, which coincided with enhanced amino acid accumulation. Our findings suggest that enhanced survival in darkness could be mediated by moderate levels of protein degradation allowing build up and slow usage of amino acids as alternative respiratory substrates, while during irreversible senescence, strong degradative processes, together with enhanced amino acid transport either to the site of their metabolization inside the leaf, or to other organs in the plant, could promote the fast progression of senescence and antagonize survival. Comparative metabolomics and gene expression analyses suggested that the senescence regulatory network downstream of PIF5 organizes these irreversible stages of leaf senescence, promoting autophagy and amino acid export, possibly by direct binding of important senescence promoting factors like ORE1 to the promoters of some of the involved genes. The failure to induce these later stages may prolong the reversible phase of darkening, thus potentially leading to drastically increased viability of individually darkened leaves under darkness for over 2 weeks.
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| 31. |
- Lotze, Heike K., et al.
(författare)
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Global ensemble projections reveal trophic amplification of ocean biomass declines with climate change
- 2019
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 116:26, s. 12907-12912
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Tidskriftsartikel (refereegranskat)abstract
- While the physical dimensions of climate change are now routinely assessed through multimodel intercomparisons, projected impacts on the global ocean ecosystem generally rely on individual models with a specific set of assumptions. To address these single-model limitations, we present standardized ensemble projections from six global marine ecosystem models forced with two Earth system models and four emission scenarios with and without fishing. We derive average biomass trends and associated uncertainties across the marine food web. Without fishing, mean global animal biomass decreased by 5% (+/- 4% SD) under low emissions and 17% (+/- 11% SD) under high emissions by 2100, with an average 5% decline for every 1 degrees C of warming. Projected biomass declines were primarily driven by increasing temperature and decreasing primary production, and were more pronounced at higher trophic levels, a process known as trophic amplification. Fishing did not substantially alter the effects of climate change. Considerable regional variation featured strong biomass increases at high latitudes and decreases at middle to low latitudes, with good model agreement on the direction of change but variable magnitude. Uncertainties due to variations in marine ecosystem and Earth system models were similar. Ensemble projections performed well compared with empirical data, emphasizing the benefits of multimodel inference to project future outcomes. Our results indicate that global ocean animal biomass consistently declines with climate change, and that these impacts are amplified at higher trophic levels. Next steps for model development include dynamic scenarios of fishing, cumulative human impacts, and the effects of management measures on future ocean biomass trends.
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| 32. |
- Malavelle, Florent F., et al.
(författare)
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Strong constraints on aerosol-cloud interactions from volcanic eruptions
- 2017
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 546:7659, s. 485-491
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Tidskriftsartikel (refereegranskat)abstract
- Aerosols have a potentially large effect on climate, particularly through their interactions with clouds, but the magnitude of this effect is highly uncertain. Large volcanic eruptions produce sulfur dioxide, which in turn produces aerosols; these eruptions thus represent a natural experiment through which to quantify aerosol-cloud interactions. Here we show that the massive 2014-2015 fissure eruption in Holuhraun, Iceland, reduced the size of liquid cloud droplets-consistent with expectations-but had no discernible effect on other cloud properties. The reduction in droplet size led to cloud brightening and global-mean radiative forcing of around -0.2 watts per square metre for September to October 2014. Changes in cloud amount or cloud liquid water path, however, were undetectable, indicating that these indirect effects, and cloud systems in general, are well buffered against aerosol changes. This result will reduce uncertainties in future climate projections, because we are now able to reject results from climate models with an excessive liquid-water-path response.
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| 33. |
- Margolskee, Alison, et al.
(författare)
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IMI - Oral biopharmaceutics tools project - Evaluation of bottom-up PBPK prediction success part 2 : An introduction to the simulation exercise and overview of results
- 2017
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Ingår i: European Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0928-0987 .- 1879-0720. ; 96, s. 610-625
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Tidskriftsartikel (refereegranskat)abstract
- Orally administered drugs are subject to a number of barriers impacting bioavailability (F-oral), causing challenges during drug and formulation development. Physiologically-based pharmacokinetic (PBPK) modelling can help during drug and formulation development by providing quantitative predictions through a systems approach. The performance of three available PBPK software packages (GI-Sim, Simcyp (R), and GastroPlus (TM)) were evaluated by comparing simulated and observed pharmacokinetic (PK) parameters. Since the availability of input parameters was heterogeneous and highly variable, caution is required when interpreting the results of this exercise. Additionally, this prospective simulation exercise may not be representative of prospective modelling in industry, as API information was limited to sparse details. 43 active pharmaceutical ingredients (APIs) from the OrBiTo database were selected for the exercise. Over 4000 simulation output files were generated, representing over 2550 study arm-institution-software combinations and approximately 600 human clinical study arms simulated with overlap. 84% of the simulated study arms represented administration of immediate release formulations, 11% prolonged or delayed release, and 5% intravenous (i.v.). Higher percentages of i.v. predicted area under the curve (AUC) were within two-fold of observed (52.9%) compared to per oral (p.o.) (37.2%), however, F-oral and relative AUC (F-rel) between p.o. formulations and solutions were generally well predicted (64.7% and 75.0%). Predictive performance declined progressing from i.v. to solution and immediate release tablet, indicating the compounding error with each layer of complexity. Overall performance was comparable to previous large-scale evaluations. A general overprediction of AUC was observed with average fold error (AFE) of 1.56 over all simulations. AFE ranged from 0.0361 to 64.0 across the 43 APIs, with 25 showing overpredictions. Discrepancies between software packages were observed for a few APIs, the largest being 606, 171, and 81.7-fold differences in AFE between SimCYP and GI-Sim, however average performance was relatively consistent across the three software platforms.
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| 34. |
- Massironi, Matteo, et al.
(författare)
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Two independent and primitive envelopes of the bilobate nucleus of comet 67P
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 526:7573, s. 402-405
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Tidskriftsartikel (refereegranskat)abstract
- The factors shaping cometary nuclei are still largely unknown, but could be the result of concurrent effects of evolutionary(1,2) and primordial processes(3,4). The peculiar bilobed shape of comet 67P/Churyumov-Gerasimenko may be the result of the fusion of two objects that were once separate or the result of a localized excavation by outgassing at the interface between the two lobes(5). Here we report that the comet's major lobe is enveloped by a nearly continuous set of strata, up to 650 metres thick, which are independent of an analogous stratified envelope on the minor lobe. Gravity vectors computed for the two lobes separately are closer to perpendicular to the strata than those calculated for the entire nucleus and adjacent to the neck separating the two lobes. Therefore comet 67P/Churyumov-Gerasimenko is an accreted body of two distinct objects with 'onion-like' stratification, which formed before they merged. We conclude that gentle, low-velocity collisions occurred between two fully formed kilometre-sized cometesimals in the early stages of the Solar System. The notable structural similarities between the two lobes of comet 67P/Churyumov-Gerasimenko indicate that the early-forming cometesimals experienced similar primordial stratified accretion, even though they formed independently.
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| 35. |
- ODonnell, Michael, et al.
(författare)
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Registered Replication Report: Dijksterhuis and van Knippenberg (1998)
- 2018
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Ingår i: Perspectives on Psychological Science. - : SAGE PUBLICATIONS LTD. - 1745-6916 .- 1745-6924. ; 13:2, s. 268-294
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Tidskriftsartikel (refereegranskat)abstract
- Dijksterhuis and van Knippenberg (1998) reported that participants primed with a category associated with intelligence (professor) subsequently performed 13% better on a trivia test than participants primed with a category associated with a lack of intelligence (soccer hooligans). In two unpublished replications of this study designed to verify the appropriate testing procedures, Dijksterhuis, van Knippenberg, and Holland observed a smaller difference between conditions (2%-3%) as well as a gender difference: Men showed the effect (9.3% and 7.6%), but women did not (0.3% and -0.3%). The procedure used in those replications served as the basis for this multilab Registered Replication Report. A total of 40 laboratories collected data for this project, and 23 of these laboratories met all inclusion criteria. Here we report the meta-analytic results for those 23 direct replications (total N = 4,493), which tested whether performance on a 30-item general-knowledge trivia task differed between these two priming conditions (results of supplementary analyses of the data from all 40 labs, N = 6,454, are also reported). We observed no overall difference in trivia performance between participants primed with the professor category and those primed with the hooligan category (0.14%) and no moderation by gender.
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| 36. |
- Pfeifer, Marion, et al.
(författare)
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Tropical forest canopies and their relationships with climate and disturbance : results from a global dataset of consistent field-based measurements
- 2018
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Ingår i: Forest Ecosystems. - : Elsevier BV. - 2095-6355 .- 2197-5620. ; 5:7
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundCanopy structure, defined by leaf area index (LAI), fractional vegetation cover (FCover) and fraction of absorbed photosynthetically active radiation (fAPAR), regulates a wide range of forest functions and ecosystem services. Spatially consistent field-measurements of canopy structure are however lacking, particularly for the tropics.MethodsHere, we introduce the Global LAI database: a global dataset of field-based canopy structure measurements spanning tropical forests in four continents (Africa, Asia, Australia and the Americas). We use these measurements to test for climate dependencies within and across continents, and to test for the potential of anthropogenic disturbance and forest protection to modulate those dependences.ResultsUsing data collected from 887 tropical forest plots, we show that maximum water deficit, defined across the most arid months of the year, is an important predictor of canopy structure, with all three canopy attributes declining significantly with increasing water deficit. Canopy attributes also increase with minimum temperature, and with the protection of forests according to both active (within protected areas) and passive measures (through topography). Once protection and continent effects are accounted for, other anthropogenic measures (e.g. human population) do not improve the model.ConclusionsWe conclude that canopy structure in the tropics is primarily a consequence of forest adaptation to the maximum water deficits historically experienced within a given region. Climate change, and in particular changes in drought regimes may thus affect forest structure and function, but forest protection may offer some resilience against this effect.
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| 37. |
- Providencia, Rui, et al.
(författare)
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Usefulness of a clinical risk score to predict the response to cardiac resynchronization therapy
- 2018
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Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273. ; 260, s. 82-87
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Tidskriftsartikel (refereegranskat)abstract
- Background: Almost 1/3 of heart failure patients fail to respond to cardiac resynchronization therapy (CRT). A simple clinical score to predict who these patients are at the moment of referral or at time of implant may be of importance for early optimization of their management. Methods: Observational study. A risk score was derived from factors associated to CRT response. The derivation cohort was composed of 1301 patients implanted with a CRT defibrillator in a multi-center French cohort-study. External validation of this score and assessment of its association with CRT response and all-cause mortality and/or heart transplant was performed in 1959 CRT patients implanted in 4 high-volume European centers. Results: Independent predictors of CRT response in the derivation cohort were: female gender (OR = 2.08, 95% CI 1.26–3.45), NYHA class ≤ III (OR = 2.71, 95% CI 1.63–4.52), left ventricular ejection fraction ≥ 25% (OR = 1.75, 95% CI 1.27–2.41), QRS duration ≥ 150 ms (OR = 1.70, 95% CI 1.25–2.30) and estimated glomerular filtration rate ≥ 60 mL/min (OR = 2.01, 95% CI 1.48–2.72). Each was assigned 1 point. External validation showed good calibration (Hosmer–Lemeshow test-P = 0.95), accuracy (Brier score = 0.19) and discrimination (c-statistic = 0.67), with CRT response increasing progressively from 37.5% in patients with a score of 0 to 91.9% among those with score of 5 (Gamma for trend = 0.44, P < 0.001). Similar results were observed regarding all-cause mortality or heart transplant. Conclusion: The ScREEN score (Sex category, Renal function, ECG/QRS width, Ejection fraction and NYHA class) is composed of widely validated, easy to obtain predictors of CRT response, and predicts CRT response and overall mortality. It should be helpful in facilitating early consideration of alternative therapies for predicted non-responders to CRT therapy.
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| 38. |
- Sampson, Joshua N., et al.
(författare)
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Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for 13 Cancer Types
- 2015
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 107:12
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Tidskriftsartikel (refereegranskat)abstract
- Background: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites. Methods: Between 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association studies (GWAS) for 49 492 cancer case patients and 34 131 control patients. We apply novel mixed model methodology (GCTA) to this GWAS data to estimate the heritability of individual cancers, as well as the proportion of heritability attributable to cigarette smoking in smoking-related cancers, and the genetic correlation between pairs of cancers. Results: GWAS heritability was statistically significant at nearly all sites, with the estimates of array-based heritability, h(l)(2), on the liability threshold (LT) scale ranging from 0.05 to 0.38. Estimating the combined heritability of multiple smoking characteristics, we calculate that at least 24% (95% confidence interval [CI] = 14% to 37%) and 7% (95% CI = 4% to 11%) of the heritability for lung and bladder cancer, respectively, can be attributed to genetic determinants of smoking. Most pairs of cancers studied did not show evidence of strong genetic correlation. We found only four pairs of cancers with marginally statistically significant correlations, specifically kidney and testes (rho = 0.73, SE = 0.28), diffuse large B-cell lymphoma (DLBCL) and pediatric osteosarcoma (rho = 0.53, SE = 0.21), DLBCL and chronic lymphocytic leukemia (CLL) (rho = 0.51, SE = 0.18), and bladder and lung (rho = 0.35, SE = 0.14). Correlation analysis also indicates that the genetic architecture of lung cancer differs between a smoking population of European ancestry and a nonsmoking Asian population, allowing for the possibility that the genetic etiology for the same disease can vary by population and environmental exposures. Conclusion: Our results provide important insights into the genetic architecture of cancers and suggest new avenues for investigation.
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| 39. |
- Sanchez-Cano, Beatriz, et al.
(författare)
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Origin of the Extended Mars Radar Blackout of September 2017
- 2019
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Ingår i: Journal of Geophysical Research - Space Physics. - : AMER GEOPHYSICAL UNION. - 2169-9380 .- 2169-9402. ; 124:6, s. 4556-4568
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Tidskriftsartikel (refereegranskat)abstract
- The Mars Advanced Radar for Subsurface and Ionosphere Sounding (MARSIS) onboard Mars Express, which operates between 0.1 and 5.5 MHz, suffered from a complete blackout for 10 days in September 2017 when observing on the nightside (a rare occurrence). Moreover, the Shallow Radar (SHARAD) onboard the Mars Reconnaissance Orbiter, which operates at 20 MHz, also suffered a blackout for three days when operating on both dayside and nightside. We propose that these blackouts are caused by solar energetic particles of few tens of keV and above associated with an extreme space weather event between 10 and 22 September 2017, as recorded by the Mars Atmosphere and Volatile EvolutioN (MAVEN) mission. Numerical simulations of energetic electron precipitation predict that a lower O-2(+) nighttime ionospheric layer of magnitude similar to 10(10) m(-3) peaking at similar to 90-km altitude is produced. Consequently, such a layer would absorb radar signals at high frequencies and explain the blackouts. The peak absorption level is found to be at 70-km altitude. Plain Language Summary Several instrument operations, as well as communication systems with rovers at the surface, depend on radio signals that propagate throughout the atmosphere of Mars. This is the case also for two radars that are currently working in Mars' orbit, sounding the ionosphere, surface, and subsurface of the planet. In mid-September 2017, a powerful solar storm hit Mars, producing a large amount of energetic particle precipitation over a 10-day period. We have found that high-energy electrons ionized the atmosphere of Mars, creating a dense layer of ions and electrons at similar to 90 km on the Martian nightside. This layer attenuated radar signals continuously for 10 days, stopping the radars to receive any signal from the planetary surface. In this work, we assess the properties of this layer in order to understand the implications of this kind of phenomenon for radar performance and communications.
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| 40. |
- Sierks, Holger, et al.
(författare)
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On the nucleus structure and activity of comet 67P/Churyumov-Gerasimenko
- 2015
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 347:6220
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Tidskriftsartikel (refereegranskat)abstract
- Images from the OSIRIS scientific imaging system onboard Rosetta show that the nucleus of 67P/Churyumov-Gerasimenko consists of two lobes connected by a short neck. The nucleus has a bulk density less than half that of water. Activity at a distance from the Sun of >3 astronomical units is predominantly from the neck, where jets have been seen consistently. The nucleus rotates about the principal axis of momentum. The surface morphology suggests that the removal of larger volumes of material, possibly via explosive release of subsurface pressure or via creation of overhangs by sublimation, may be a major mass loss process. The shape raises the question of whether the two lobes represent a contact binary formed 4.5 billion years ago, or a single body where a gap has evolved via mass loss.
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| 41. |
- Soto Valero, César, et al.
(författare)
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The Emergence of Software Diversity inMaven Central
- 2019
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Ingår i: 16th International Conference on Mining Software Repositories. - Montréal, QC, Canada : IEEE conference proceedings. ; , s. 333-343
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Konferensbidrag (refereegranskat)abstract
- Maven artifacts are immutable: an artifact that is uploaded on Maven Central cannot be removed nor modified. The only way for developers to upgrade their library is to releasea new version. Consequently, Maven Central accumulates all the versions of all the libraries that are published there, and applications that declare a dependency towards a library can pick any version. In this work, we hypothesize that the immutability of Maven artifacts and the ability to choose any version naturally support the emergence of software diversity within Maven Central. We analyze 1,487,956 artifacts that represent all the versions of 73,653 libraries. We observe that more than 30% of libraries have multiple versions that are actively used by latest artifacts. In the case of popular libraries, more than 50% of their versions are used. We also observe that more than 17% of libraries have several versions that are significantly more used than the other versions. Our results indicate that the immutability of artifacts in Maven Central does support a sustained level of diversity among versions of libraries in the repository.
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| 42. |
- Sylvestre-Gonon, Elodie, et al.
(författare)
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Functional, Structural and Biochemical Features of Plant Serinyl-Glutathione Transferases
- 2019
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Ingår i: Frontiers in Plant Science. - : Frontiers Media S.A.. - 1664-462X. ; 10
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Forskningsöversikt (refereegranskat)abstract
- Glutathione transferases (GSTs) belong to a ubiquitous multigenic family of enzymes involved in diverse biological processes including xenobiotic detoxification and secondary metabolism. A canonical GST is formed by two domains, the N-terminal one adopting a thioredoxin (TRX) fold and the C-terminal one an all-helical structure. The most recent genomic and phylogenetic analysis based on this domain organization allowed the classification of the GST family into 14 classes in terrestrial plants. These GSTs are further distinguished based on the presence of the ancestral cysteine (Cys-GSTs) present in TRX family proteins or on its substitution by a serine (Ser-GSTs). Cys-GSTs catalyze the reduction of dehydroascorbate and deglutathionylation reactions whereas Ser-GSTs catalyze glutathione conjugation reactions and eventually have peroxidase activity, both activities being important for stress tolerance or herbicide detoxification. Through non-catalytic, so-called ligandin properties, numerous plant GSTs also participate in the binding and transport of small heterocyclic ligands such as flavonoids including anthocyanins, and polyphenols. So far, this function has likely been underestimated compared to the other documented roles of GSTs. In this review, we compiled data concerning the known enzymatic and structural properties as well as the biochemical and physiological functions associated to plant GSTs having a conserved serine in their active site.
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| 43. |
- Thomas, Nicolas, et al.
(författare)
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The morphological diversity of comet 67P/Churyumov-Gerasimenko
- 2015
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 347:6220
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Tidskriftsartikel (refereegranskat)abstract
- Images of comet 67P/Churyumov-Gerasimenko acquired by the OSIRIS (Optical, Spectroscopic and Infrared Remote Imaging System) imaging system onboard the European Space Agency's Rosetta spacecraft at scales of better than 0.8 meter per pixel show a wide variety of different structures and textures. The data show the importance of airfall, surface dust transport, mass wasting, and insolation weathering for cometary surface evolution, and they offer some support for subsurface fluidization models and mass loss through the ejection of large chunks of material.
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| 44. |
- Toledo-Redondo, Sergio, et al.
(författare)
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Energy budget and mechanisms of cold ion heating in asymmetric magnetic reconnection
- 2017
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Ingår i: Journal of Geophysical Research - Space Physics. - : American Geophysical Union (AGU). - 2169-9380 .- 2169-9402. ; 122:9, s. 9396-9413
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Tidskriftsartikel (refereegranskat)abstract
- Cold ions (few tens of eV) of ionospheric origin are commonly observed on the magnetospheric side of the Earth's dayside magnetopause. As a result, they can participate in magnetic reconnection, changing locally the reconnection rate and being accelerated and heated. We present four events where cold ion heating was observed by the Magnetospheric Multiscale mission, associated with the magnetospheric Hall E field region of magnetic reconnection. For two of the events the cold ion density was small compared to the magnetosheath density, and the cold ions were heated roughly to the same temperature as magnetosheath ions inside the exhaust. On the other hand, for the other two events the cold ion density was comparable to the magnetosheath density and the cold ion heating observed was significantly smaller. Magnetic reconnection converts magnetic energy into particle energy, and ion heating is known to dominate the energy partition. We find that at least 10-25% of the energy spent by reconnection into ion heating went into magnetospheric cold ion heating. The total energy budget for cold ions may be even higher when properly accounting for the heavier species, namely helium and oxygen. Large E field fluctuations are observed in this cold ion heating region, i.e., gradients and waves, that are likely the source of particle energization. Plain Language Summary The magnetic field of Earth creates a natural shield that isolates and protects us from the particles and fields coming from our star, the Sun. This natural shield is called the magnetosphere and is filled by plasma. The particles coming from the Sun form another plasma called the solar wind and are usually deviated around the magnetosphere. However, under certain circumstances these two plasmas can reconnect (magnetic reconnection), and part of the energy and mass of the two plasmas is interchanged. Magnetic reconnection is the driver of storms and substorms inside the magnetosphere. In this work, we investigate what occurs to particles of very low energy (cold ions) of ionospheric origin when they reach the reconnecting boundary of the magnetosphere. It is found that they are energized and take an important part of the energy spent in reconnecting the plasmas. The plasma boundary develops spatial structures and emits waves that are able to heat the cold ions. Once heated, these cold ions irreversibly will escape the Earth's magnetosphere to never come back to Earth.
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| 45. |
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| 46. |
- Vincent, Jean-Baptiste, et al.
(författare)
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Large heterogeneities in comet 67P as revealed by active pits from sinkhole collapse
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 523:7558, s. 63-66
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Tidskriftsartikel (refereegranskat)abstract
- Pits have been observed on many cometary nuclei mapped by spacecraft(1-4). It has been argued that cometary pits are a signature of endogenic activity, rather than impact craters such as those on planetary and asteroid surfaces. Impact experiments(5,6) andmodels(7,8) cannot reproduce the shapes of most of the observed cometary pits, and the predicted collision rates imply that few of the pits are related to impacts(8,9). Alternative mechanisms like explosive activity(10) have been suggested, but the driving process remains unknown. Here we report that pits on comet 67P/Churyumov-Gerasimenko are active, and probably created by a sinkhole process, possibly accompanied by outbursts. We argue that after formation, pits expand slowly in diameter, owing to sublimation-driven retreat of the walls. Therefore, pits characterize how eroded the surface is: a fresh cometary surface will have a ragged structure with many pits, while an evolved surface will look smoother. The size and spatial distribution of pits imply that large heterogeneities exist in the physical, structural or compositional properties of the first few hundred metres below the current nucleus surface.
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| 47. |
- Voigt, Aiko, et al.
(författare)
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Fast and slow shifts of the zonal-mean intertropical convergence zone in response to an idealized anthropogenic aerosol
- 2017
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Ingår i: Journal of Advances in Modeling Earth Systems. - 1942-2466. ; 9:2, s. 870-892
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Tidskriftsartikel (refereegranskat)abstract
- Previous modeling work showed that aerosol can affect the position of the tropical rain belt, i.e., the intertropical convergence zone (ITCZ). Yet it remains unclear which aspects of the aerosol impact are robust across models, and which are not. Here we present simulations with seven comprehensive atmosphere models that study the fast and slow impacts of an idealized anthropogenic aerosol on the zonalmean ITCZ position. The fast impact, which results from aerosol atmospheric heating and land cooling before sea-surface temperature (SST) has time to respond, causes a northward ITCZ shift. Yet the fast impact is compensated locally by decreased evaporation over the ocean, and a clear northward shift is only found for an unrealistically large aerosol forcing. The local compensation implies that while models differ in atmospheric aerosol heating, this does not contribute to model differences in the ITCZ shift. The slow impact includes the aerosol impact on the ocean surface energy balance and is mediated by SST changes. The slow impact is an order of magnitude more effective than the fast impact and causes a clear southward ITCZ shift for realistic aerosol forcing. Models agree well on the slow ITCZ shift when perturbed with the same SST pattern. However, an energetic analysis suggests that the slow ITCZ shifts would be substantially more modeldependent in interactive-SST setups due to model differences in clear-sky radiative transfer and clouds. We also discuss implications for the representation of aerosol in climate models and attributions of recent observed ITCZ shifts to aerosol.
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| 48. |
- Zannini, Flavien, et al.
(författare)
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In vitro alkylation methods for assessing the protein redox state
- 2017. - 1
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Ingår i: Photorespiration. - New York : Humana Press. - 9781493972241 - 9781493972258 ; , s. 51-64
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Bokkapitel (refereegranskat)abstract
- Cysteines are important residues for protein structure, function, and regulation. Owing to their modified reactivity, some cysteines can undergo very diverse redox posttranslational modifications, including the reversible formation of disulfide bonds, a widespread protein regulatory process as well exemplified in plant chloroplasts for Calvin-Benson cycle enzymes. Both core- and peripheral-photorespiratory enzymes possess conserved cysteines, some of which have been identified as being subject to oxidative modifications. This is not surprising considering their presence in subcellular compartments where the production of reactive species can be important. However, in most cases, the types of modifications and their biochemical effect on protein activity have not been validated, meaning that the possible impact of these modifications in a complex physiological context, such as photorespiration, remains obscure. We here describe a detailed set of protocols for alkylation methods that have been used so far to (1) study the protein cysteine redox state either in vitro by submitting purified recombinant proteins to reducing/oxidation treatments or in vivo by western blots on protein extracts from plants subject to environmental constraints, and its dependency on the two major reducing systems in the cell, i.e., the thioredoxin and glutathione/glutaredoxin systems, and (2) determine two key redox parameters, i.e., the cysteine pKa and the redox midpoint potential.
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