| 1. |
- Abugabbara, Marwan, et al.
(författare)
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How to develop fifth-generation district heating and cooling in Sweden? : Application review and best practices proposed by middle agents
- 2023
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Ingår i: Energy Reports. - : Elsevier Ltd. - 2352-4847. ; 9, s. 4971-4983
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Tidskriftsartikel (refereegranskat)abstract
- Sweden has an ambitious plan to fully decarbonise district heating by 2030 and to contribute with negative emissions of greenhouse gases in 2050. The vagaries of the energy market associated with climate, political, and social changes entail cross-sectoral integration that can fulfill these national targets. Fifth-generation district heating and cooling (5GDHC) is a relatively new concept of district energy systems that features a simultaneous supply of heating and cooling using power-to-heat technologies. This paper presents best practices for developing 5GDHC systems in Sweden to reach a consensus view on these systems among all stakeholders. A mixed-method combining best practice and roadmapping workshops has been used to disseminate mixed knowledge and experience from middle agents representing industry professionals and practitioners. Four successful implementations of 5GDHC systems are demonstrated and the important learned lessons are shared. The best practices are outlined for system planning, system modeling and simulation, prevailing business models for energy communities, and system monitoring. A roadmap from the middle agents’ point of view is composed and can be utilised to establish industry standards and common regulatory frameworks. © 2023 The Author(s)
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| 2. |
- Blanton, Michael R., et al.
(författare)
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Sloan Digital Sky Survey IV : Mapping the Milky Way, Nearby Galaxies, and the Distant Universe
- 2017
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Ingår i: Astronomical Journal. - : IOP Publishing Ltd. - 0004-6256 .- 1538-3881. ; 154:1
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Tidskriftsartikel (refereegranskat)abstract
- We describe the Sloan Digital Sky Survey IV (SDSS-IV), a project encompassing three major spectroscopic programs. The Apache Point Observatory Galactic Evolution Experiment 2 (APOGEE-2) is observing hundreds of thousands of Milky Way stars at high resolution and. high signal-to-noise ratios in the near-infrared. The Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey is obtaining spatially resolved spectroscopy for thousands of nearby galaxies (median z similar to 0.03). The extended Baryon Oscillation Spectroscopic Survey (eBOSS) is mapping the galaxy, quasar, and neutral gas distributions between z similar to 0.6 and 3.5 to constrain cosmology using baryon acoustic oscillations, redshift space distortions, and the shape of the power spectrum. Within eBOSS, we are conducting two major subprograms: the SPectroscopic IDentification of eROSITA Sources (SPIDERS), investigating X-ray AGNs. and galaxies in X-ray clusters, and the Time Domain Spectroscopic Survey (TDSS), obtaining spectra of variable sources. All programs use the 2.5 m Sloan Foundation Telescope at the. Apache Point Observatory; observations there began in Summer 2014. APOGEE-2 also operates a second near-infrared spectrograph at the 2.5 m du Pont Telescope at Las Campanas Observatory, with observations beginning in early 2017. Observations at both facilities are scheduled to continue through 2020. In keeping with previous SDSS policy, SDSS-IV provides regularly scheduled public data releases; the first one, Data Release 13, was made available in 2016 July.
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| 3. |
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| 4. |
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- 2019
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Tidskriftsartikel (refereegranskat)
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| 5. |
- Abelein, Axel, et al.
(författare)
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Formation of dynamic soluble surfactant-induced amyloid β peptide aggregation intermediates
- 2013
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Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 288:32, s. 23518-23528
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Tidskriftsartikel (refereegranskat)abstract
- Intermediate amyloidogenic states along the amyloid β peptide (Aβ) aggregation pathway have been shown to be linked to neurotoxicity. To shed more light on the different structures that may arise during Aβ aggregation, we here investigate surfactant-induced Aβ aggregation. This process leads to co-aggregates featuring a β-structure motif that is characteristic for mature amyloid-like structures. Surfactants induce secondary structure in Aβ in a concentration-dependent manner, from predominantly random coil at low surfactant concentration, via β-structure to the fully formed α-helical state at high surfactant concentration. The β-rich state is the most aggregation-prone as monitored by thioflavin T fluorescence. Small angle x-ray scattering reveals initial globular structures of surfactant-Aβ co-aggregated oligomers and formation of elongated fibrils during a slow aggregation process. Alongside this slow (minutes to hours time scale) fibrillation process, much faster dynamic exchange (k(ex) ∼1100 s(-1)) takes place between free and co-aggregate-bound peptide. The two hydrophobic segments of the peptide are directly involved in the chemical exchange and interact with the hydrophobic part of the co-aggregates. Our findings suggest a model for surfactant-induced aggregation where free peptide and surfactant initially co-aggregate to dynamic globular oligomers and eventually form elongated fibrils. When interacting with β-structure promoting substances, such as surfactants, Aβ is kinetically driven toward an aggregation-prone state.
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| 6. |
- Beal, Jacob, et al.
(författare)
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Robust estimation of bacterial cell count from optical density
- 2020
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Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
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Tidskriftsartikel (refereegranskat)abstract
- Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
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| 7. |
- Carlsson, Axel C, et al.
(författare)
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10-Year Associations between Tumor Necrosis Factor Receptors 1 and 2 and Cardiovascular Events in Patients with Stable Coronary Heart Disease : A CLARICOR (Effect of Clarithromycin on Mortality and Morbidity in Patients With Ischemic Heart Disease) Trial Substudy.
- 2018
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Ingår i: Journal of the American Heart Association. - 2047-9980. ; 7:9
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: We aimed to assess the associations and predictive powers between the soluble receptors for tumor necrosis factor (TNF)-α (TNFR1 and TNFR2) and cardiovascular outcomes in patients with stable coronary heart disease.METHODS AND RESULTS: CLARICOR (Effect of Clarithromycin on Mortality and Morbidity in Patients With Ischemic Heart Disease) is a randomized clinical trial comparing clarithromycin with placebo in patients with stable coronary heart disease. The primary outcome was a composite of nonfatal acute myocardial infarction, unstable angina pectoris, cerebrovascular disease, and all-cause mortality. Patients were followed up for 10 years; discovery sample, those assigned placebo (1204 events in n=1998); and replication sample, those assigned clarithromycin (1220 events in n=1979). We used Cox regression adjusted for C-reactive protein level, established cardiovascular risk factors, kidney function, and cardiovascular drugs. After adjustments, higher serum levels of TNFR1 and TNFR2 were associated with the composite outcome in the discovery sample (hazard ratio per SD increase, 1.13; 95% confidence interval, 1.05-1.22; P=0.001 for TNFR1; hazard ratio, 1.16; 95% confidence interval, 1.08-1.24; P<0.001 for TNFR2). The associations were similar in the replication sample. The associations with the composite outcome were mainly driven by acute myocardial infarction, cardiovascular mortality, and noncardiovascular mortality. The addition of TNFR1 and TNFR2 to established cardiovascular risk factors improved prediction only modestly (<1%).CONCLUSIONS: Increased concentrations of circulating TNFR1 and TNFR2 were associated with increased risks of cardiovascular events and mortality in patients with stable coronary heart disease. Yet, the utility of measuring TNFR1 and TNFR2 to improve risk prediction in these patients appears limited.CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00121550.
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| 8. |
- Christensen, Axel Norlund, et al.
(författare)
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Thermally induced phase transitions of barium oxalates
- 2011
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Ingår i: Solid State Sciences. - : Elsevier BV. - 1873-3085 .- 1293-2558. ; 13:7, s. 1407-1413
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Tidskriftsartikel (refereegranskat)abstract
- The thermal decomposition of BaC2O4 center dot 3.5H(2)O and BaC2O4 center dot 0.5H(2)O was investigated using in situ synchrotron X-ray and neutron powder diffraction. The decomposition routes for the barium oxalate hydrates were observed to depend on the applied heating rate. Thermal decomposition of BaC2O4 center dot 0.5H(2)O showed transformation to alpha-BaC2O4 and to beta-BaC2O4 prior to the formation of BaCO3. The decomposition of BaC2O4 center dot 3.5H(2)O showed formation of BaC2O4 center dot 0.5H(2)O at 58 degrees C and the hemi hydrate transforms to alpha-BaC2O4 at 187 degrees C using a relatively fast heating rate of 6.25 degrees C/min. The phase transitions were more complicated using lower heating rate, which also reveal formation of beta-BaC2O4 coexisting with alpha-BaC2O4 along with an unidentified compound. Heating alpha- and beta-BaC2O4 to higher temperatures (T > 400 degrees C) produced BaCO3. A sample of alpha-BaC2O4 was prepared in situ by thermal decomposition of BaC2O4 center dot 3.5H(2)O on a powder neutron diffractometer. The neutron diffraction data has broad diffraction peaks due to small crystallite sizes and overlapping Bragg reflections. [A structural model for alpha-BaC2O4 was derived from the neutron pattern, triclinic, space group P-1, a = 5.127(7), b = 8.905(12), c = 9.068(12) angstrom, alpha = 82.74(1), beta = 99.46(2), gamma = 100.10(1)degrees measured at T= 300 degrees C. The average Ba-O distances are 2.84(3) angstrom and 2.66(3) angstrom for Ba 1 and Ba2 respectively, C-O atom distances in the oxalate ions were found in the range 1.25(3)-1.26(4) angstrom, and C-C distances were 1.60(1)-1.61(1) angstrom]. (C) 2011 Elsevier Masson SAS. All rights reserved.
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| 9. |
- Fokkema, Marieke L., et al.
(författare)
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Outcome after percutaneous coronary intervention for different indications : long-term results from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR)
- 2016
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Ingår i: EuroIntervention. - Toulouse, France : Europa Edition. - 1774-024X .- 1969-6213. ; 12:3, s. 303-311
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Tidskriftsartikel (refereegranskat)abstract
- Aims: The aim of this study was to evaluate clinical outcome for different indications for PCI in an unselected, nationwide PCI population at short- and long-term follow-up.Methods and results: We evaluated clinical outcome up to six years after PCI in all patients undergoing a PCI procedure for different indications in Sweden between 2006 and 2010. A total of 70,479 patients were treated for stable coronary artery disease (CAD) (21.0%), unstable angina (11.0%), non-ST-elevation myocardial infarction (NSTEMI) (36.6%) and ST-elevation myocardial infarction (STEMI) (31.4%). Mortality was higher in STEMI patients at one year after PCI (9.6%) compared to NSTEMI (4.7%), unstable angina (2.2%) and stable CAD (2.0%). At one year after PCI until the end of follow-up, the adjusted mortality risk (one to six years after PCI) and the risk of myocardial infarction were comparable between NSTEMI and STEMI patients and lower in patients with unstable angina and stable CAD. The adjusted risk of stent thrombosis and heart failure was highest in STEMI patients.Conclusions: The risk of short-term mortality, heart failure and stent thrombosis is highest for STEMI patients after PCI. Therapies to reduce stent thrombosis and heart failure appear to be most important in decreasing mortality in patients with STEMI or NSTEMI undergoing PCI.
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| 10. |
- Fokkema, Marieke L, et al.
(författare)
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Population Trends in Percutaneous Coronary Intervention 20-Year Results From the SCAAR (Swedish Coronary Angiography and Angioplasty Registry)
- 2013
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Ingår i: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097 .- 1558-3597. ; 61:12, s. 1222-1230
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Tidskriftsartikel (refereegranskat)abstract
- Objectives The aim of this study was to describe the characteristics and outcome of all consecutive patients treated with percutaneous coronary intervention (PCI) in an unselected nationwide cohort over the past 2 decades. Background Over the last 20 years, treatment with PCI has evolved dramatically, but the change in patient characteristics has not been well described. Methods We included all patients undergoing a PCI procedure for the first time between January 1990 and December 2010 from the SCAAR (Swedish Coronary Angiography and Angioplasty Registry). Patients were divided into different cohorts on the basis of the year of the first PCI procedure. Results A total of 144,039 patients was included. The mean age increased from 60.1 +/- 9.9 years in 1990 to 1995 to 67.1 +/- 11.2 years in 2009 to 2010. The proportion of patients presenting with unstable coronary artery disease and ST-segment elevation myocardial infarction increased from 27.4% and 6.2% to 47.7% and 32.5%, respectively. Diabetes mellitus and multivessel disease were more often present in the later-year cohorts. The 1-year mortality increased from 2.2% in 1990 to 1995 to 5.9% in 2009 to 2010, but after adjustment for age and indication, a modest decrease was shown, mainly in ST-segment elevation myocardial infarction patients. Conclusions Characteristics of PCI patients have changed substantially over time, reflecting the establishment of new evidence. The increasing age and proportion of patients undergoing PCI for acute coronary syndromes greatly influence outcome. Understanding the changing patient characteristics is important for the translation of evidence to real-world clinical practice. (J Am Coll Cardiol 2013; 61: 1222-30) (C) 2013 by the American College of Cardiology Foundation
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| 11. |
- Gao, Hong, et al.
(författare)
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The landscape of tolerated genetic variation in humans and primates
- 2023
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 380:6648
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Tidskriftsartikel (refereegranskat)abstract
- Personalized genome sequencing has revealed millions of genetic differences between individuals, but our understanding of their clinical relevance remains largely incomplete. To systematically decipher the effects of human genetic variants, we obtained whole-genome sequencing data for 809 individuals from 233 primate species and identified 4.3 million common protein-altering variants with orthologs in humans. We show that these variants can be inferred to have nondeleterious effects in humans based on their presence at high allele frequencies in other primate populations. We use this resource to classify 6% of all possible human protein-altering variants as likely benign and impute the pathogenicity of the remaining 94% of variants with deep learning, achieving state-of-the-art accuracy for diagnosing pathogenic variants in patients with genetic diseases.
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| 12. |
- Hydbom, Sofia, et al.
(författare)
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Reduced tillage stimulated symbiotic fungi and microbial saprotrophs, but did not lead to a shift in the saprotrophic microorganism community structure
- 2017
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Ingår i: Applied Soil Ecology. - : Elsevier BV. - 0929-1393 .- 1873-0272. ; 119, s. 104-114
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Tidskriftsartikel (refereegranskat)abstract
- The need for sustainable agricultural systems, which for example enhance soil organic carbon (SOC) content, has increased the interest for management with reduced tillage. In this study we used a Swedish long-term (20 yrs.) systems experiment, including reduced tillage (harrowing 10 cm) and plowing (moldboard plow 0–20 cm) combined with three levels of nitrogen (N) fertilization. With this setup we tested if (1) the arbuscular mycorrhizal fungi (AMF) concentration and (2) the fungi to bacteria (F:B) ratio would be higher under reduced tillage than under conventional tillage, and if this would be associated with higher SOC concentrations. We also tested if (3) the microbial biomass C close to the surface would be higher under reduced tillage than conventional tillage. Furthermore, since disturbance can reduce respiration and microbial growth we tested if (4) this occurred in our reduced tillage system. In addition, we tested if (5) fertilization increased the growth rate of fungi and decreased that of bacteria. We collected soil samples in July and October and found that the microbial biomass C, measured in October only, was higher close to the surface in the reduced tillage treatment and so was the microbial respiration. The fungal and bacterial growth rate, on the other hand, were not affected by tillage treatment. Fertilization did not affect the bacterial growth rate but did have a positive effect on fungal growth rate. In accordance with our expectations reduced tillage had a stimulating effect on AMF and saprotrophic fungi, and contrary to our expectation, also bacteria were positively affected by reduced tillage. In line with the unchanged F:B ratio, we found no indication that even 20 years of reduced tillage increased SOC concentrations in the long term.
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| 13. |
- Jensen, Axel, et al.
(författare)
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Complex Evolutionary History With Extensive Ancestral Gene Flow in an African Primate Radiation
- 2023
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Ingår i: Molecular biology and evolution. - : Oxford University Press. - 0737-4038 .- 1537-1719. ; 40:12
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Tidskriftsartikel (refereegranskat)abstract
- Understanding the drivers of speciation is fundamental in evolutionary biology, and recent studies highlight hybridization as an important evolutionary force. Using whole-genome sequencing data from 22 species of guenons (tribe Cercopithecini), one of the world's largest primate radiations, we show that rampant gene flow characterizes their evolutionary history and identify ancient hybridization across deeply divergent lineages that differ in ecology, morphology, and karyotypes. Some hybridization events resulted in mitochondrial introgression between distant lineages, likely facilitated by cointrogression of coadapted nuclear variants. Although the genomic landscapes of introgression were largely lineage specific, we found that genes with immune functions were overrepresented in introgressing regions, in line with adaptive introgression, whereas genes involved in pigmentation and morphology may contribute to reproductive isolation. In line with reports from other systems that hybridization might facilitate diversification, we find that some of the most species-rich guenon clades are of admixed origin. This study provides important insights into the prevalence, role, and outcomes of ancestral hybridization in a large mammalian radiation.
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| 14. |
- Jensen, Axel, et al.
(författare)
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Whole genome sequencing reveals high differentiation, low levels of genetic diversity and short runs of homozygosity among Swedish wels catfish
- 2021
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Ingår i: Heredity. - : Nature Publishing Group. - 0018-067X .- 1365-2540. ; 127, s. 79-91
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Tidskriftsartikel (refereegranskat)abstract
- The use of genetic markers in the context of conservation is largely being outcompeted by whole-genome data. Comparative studies between the two are sparse, and the knowledge about potential effects of this methodology shift is limited. Here, we used whole-genome sequencing data to assess the genetic status of peripheral populations of the wels catfish (Silurus glanis), and discuss the results in light of a recent microsatellite study of the same populations. The Swedish populations of the wels catfish have suffered from severe declines during the last centuries and persists in only a few isolated water systems. Fragmented populations generally are at greater risk of extinction, for example due to loss of genetic diversity, and may thus require conservation actions. We sequenced individuals from the three remaining native populations (Baven, Eman, and Mockeln) and one reintroduced population of admixed origin (Helge a), and found that genetic diversity was highest in Eman but low overall, with strong differentiation among the populations. No signature of recent inbreeding was found, but a considerable number of short runs of homozygosity were present in all populations, likely linked to historically small population sizes and bottleneck events. Genetic substructure within any of the native populations was at best weak. Individuals from the admixed population Helge a shared most genetic ancestry with the Baven population (72%). Our results are largely in agreement with the microsatellite study, and stresses the need to protect these isolated populations at the northern edge of the distribution of the species.
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| 15. |
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| 16. |
- Jensen, M., et al.
(författare)
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Finite element convergence for the time-dependent Joule heating problem with mixed boundary conditions
- 2022
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Ingår i: Ima Journal of Numerical Analysis. - : Oxford University Press (OUP). - 0272-4979 .- 1464-3642. ; 42:1, s. 199-228
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Tidskriftsartikel (refereegranskat)abstract
- We prove strong convergence for a large class of finite element methods for the time-dependent Joule heating problem in three spatial dimensions with mixed boundary conditions on Lipschitz domains. We consider conforming subspaces for the spatial discretization and the backward Euler scheme for the temporal discretization. Furthermore, we prove uniqueness and higher regularity of the solution on creased domains and additional regularity in the interior of the domain. Due to a variational formulation with a cut-off functional, the convergence analysis does not require a discrete maximum principle, permitting approximation spaces suitable for adaptive mesh refinement, responding to the difference in regularity within the domain.
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| 17. |
- Khatibi, Ali, et al.
(författare)
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Structural and Mechanical Properties of (AlxCr1-x)2+yO3-y Coatings Grown by Reactive Cathodic Arc Evaporation in As-deposited and Annealed States
- 2013
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Ingår i: Acta Materialia. - : Elsevier. - 1359-6454 .- 1873-2453. ; 61:13, s. 4811-4822
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Tidskriftsartikel (refereegranskat)abstract
- Coatings of (AlxCr1-x)2+yO3-y with 0.51≤x≤0.84 and 0.1≤y≤0.5 were deposited on hard cemented carbides substrates in an industrial cathodic arc evaporation system from powder-metallurgy prepared Cr/Al targets in pure O2 and O2+N2 atmospheres. The substrate temperature and bias in all the deposition runs were 575 °C and -120 V, respectively. The composition of the coatings measured by energy dispersive x-ray spectroscopy and elastic recoil detection analysis was the same as that of the targets. Microstructure analyses performed by symmetrical X-ray diffraction and transmission electron microscopy showed that corundum, cubic or mixed-phase coatings formed depending on the Cr/Al ratio of the coatings and O2 flow per activetarget during deposition. The corundum phase was promoted by high Cr content and high O2 flow per target, while the cubic phase was mostly observed for high Al content and low O2 flow per active target. In situ annealing of the cubic coatings resulted in phase transformation from cubic to corundum completed in the temperature range of 900-1100 °C, while corundum coatings retained their structure in the same range of annealing temperatures. Nanoindentation hardness of the coatings with Cr/Al ratio < 0.4 was 26-28 GPa, regardless of the structure. Increasing the Cr content of the coatings resulted in increased hardness of 28-30 GPa for corundum coatings. Wear resistance testing in a turning operation showed that coatings of Al-Cr-O have improved resistance to crater wear at the cost of flank wear compared to TiAlN coatings.
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| 18. |
- Kuderna, Lukas F. K., et al.
(författare)
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A global catalog of whole-genome diversity from 233 primate species
- 2023
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 380:6648, s. 906-913
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Tidskriftsartikel (refereegranskat)abstract
- The rich diversity of morphology and behavior displayed across primate species provides an informative context in which to study the impact of genomic diversity on fundamental biological processes. Analysis of that diversity provides insight into long-standing questions in evolutionary and conservation biology and is urgent given severe threats these species are facing. Here, we present high-coverage wholegenome data from 233 primate species representing 86% of genera and all 16 families. This dataset was used, together with fossil calibration, to create a nuclear DNA phylogeny and to reassess evolutionary divergence times among primate clades. We found within-species genetic diversity across families and geographic regions to be associated with climate and sociality, but not with extinction risk. Furthermore, mutation rates differ across species, potentially influenced by effective population sizes. Lastly, we identified extensive recurrence of missense mutations previously thought to be human specific. This study will open a wide range of research avenues for future primate genomic research.
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| 19. |
- Kuderna, Lukas F. K., et al.
(författare)
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Identification of constrained sequence elements across 239 primate genomes
- 2024
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Ingår i: Nature. - : Springer Nature. - 0028-0836 .- 1476-4687. ; 625:7996, s. 735-742
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Tidskriftsartikel (refereegranskat)abstract
- Noncoding DNA is central to our understanding of human gene regulation and complex diseases1,2, and measuring the evolutionary sequence constraint can establish the functional relevance of putative regulatory elements in the human genome3,4,5,6,7,8,9. Identifying the genomic elements that have become constrained specifically in primates has been hampered by the faster evolution of noncoding DNA compared to protein-coding DNA10, the relatively short timescales separating primate species11, and the previously limited availability of whole-genome sequences12. Here we construct a whole-genome alignment of 239 species, representing nearly half of all extant species in the primate order. Using this resource, we identified human regulatory elements that are under selective constraint across primates and other mammals at a 5% false discovery rate. We detected 111,318 DNase I hypersensitivity sites and 267,410 transcription factor binding sites that are constrained specifically in primates but not across other placental mammals and validate their cis-regulatory effects on gene expression. These regulatory elements are enriched for human genetic variants that affect gene expression and complex traits and diseases. Our results highlight the important role of recent evolution in regulatory sequence elements differentiating primates, including humans, from other placental mammals.
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| 20. |
- Nilsson, Erik, 1975-, et al.
(författare)
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Pregnancy Associated Plasma Protein-A as a Cardiovascular Risk Marker in Patients with Stable Coronary Heart Disease During 10 Years Follow-Up-A CLARICOR Trial Sub-Study
- 2020
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Ingår i: Journal of Clinical Medicine. - : MDPI. - 2077-0383. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- Elevated pregnancy-associated plasma protein A (PAPP-A) is associated with mortality in acute coronary syndromes. Few studies have assessed PAPP-A in stable coronary artery disease (CAD) and results are conflicting. We assessed the 10-year prognostic relevance of PAPP-A levels in stable CAD. The CLARICOR trial was a randomized controlled clinical trial including outpatients with stable CAD, randomized to clarithromycin versus placebo. The placebo group constituted our discovery cohort (n = 1.996) and the clarithromycin group the replication cohort (n = 1.975). The composite primary outcome was first occurrence of cardiovascular event or death. In the discovery cohort, incidence rates (IR) for the composite outcome were higher in those with elevated PAPP-A (IR 12.72, 95% Confidence Interval (CI) 11.0-14.7 events/100 years) compared to lower PAPP-A (IR 8.78, 8.25-9.34), with comparable results in the replication cohort. Elevated PAPP-A was associated with increased risk of the composite outcome in both cohorts (discovery Hazard Ratio (HR) 1.45, 95% CI 1.24-1.70; replication HR 1.29, 95% CI 1.10-1.52). In models adjusted for established risk factors, these trends were attenuated. Elevated PAPP-A was associated with higher all-cause mortality in both cohorts. We conclude that elevated PAPP-A levels are associated with increased long-term mortality in stable CAD, but do not improve long-term prediction of death or cardiovascular events when added to established predictors.
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| 21. |
- Norlund Christensen, Axel, et al.
(författare)
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Formation and transformation of five different phases in the CaSO4-H2O system: Crystal structure of the subhydrate beta-CaSO4 center dot 0.5H(2)O and soluble anhydrite CaSO4
- 2008
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Ingår i: Chemistry of Materials. - : American Chemical Society (ACS). - 0897-4756 .- 1520-5002. ; 20:6, s. 2124-2132
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Tidskriftsartikel (refereegranskat)abstract
- At least five crystalline-phases can be found in the CaSO4-H2O system, which are gypsum CaSO4 center dot 2H(2)O, the subhydrates alpha- and beta-CaSO4 center dot 0.5H(2)O, and the soluble and insoluble anhydrite CaSO4. The formation of these five phases in the CaSO4-H2O system and their transformations were investigated by in situ time-resolved synchrotron radiation powder X-ray diffraction (SR-PXD) in this study. Furthermore, revised structural models for beta-CaSO4 center dot 0.5H(2)O and soluble anhydrite CaSO4 are presented. The hydration of alpha-CaSO4 center dot 0.5H(2)O was studied at 25 degrees C and showed that the reaction with H2O started immediately after mixing the two reactants and that the formation of CaSO4 center dot 2H(2)O was coupled to the depletion of alpha-CaSO4 center dot 0.5H(2)O. The thermal decomposition of CaSO4 center dot 2H(2)O was investigated in the temperature range of 25-500 degrees C and showed the fon-nation of alpha-CaSO4 center dot 0.5H(2)O followed by the formation of soluble anhydrite AIII-CaSO4, which was gradually converted to insoluble anhydrite AII-CaSO4. The thermal decomposition of alpha-CaSO4 center dot 0.5D(2)O was investigated in the temperature range of 25-500 degrees C and showed successive phase transformations to beta-CaSO4 center dot 0.5D(2)O, soluble anhydrite AIII-CaSO4, and insoluble anhydrite AII-CaS04. The two polymorphs of anhydrite coexist in the investigated temperature range of 200-500 degrees C. The hydrothermal decomposition of CaSO4 center dot 2H(2)O was investigated in the temperature range of 25-200 degrees C using a 1 M HNO3 or a 1 M LiCl solution, and in both experiments, CaSO4 center dot 2H(2)O was converted to alpha-CaSO4 center dot 0.5H(2)O and further to insoluble anhydrite AII-CaSO4. A structural model for beta-CaSO4 center dot 0.5H(2)O is proposed on the basis of SR-PXD data and a trigonal unit cell (in hexagonal setting) a = 6.93145(3), c = 12.736 17(4) angstrom, Z = 6, and space group P3(1). A structural model for soluble anhydrite AIII-CaSO4 is also proposed on the basis of powder neutron diffraction data, and a hexagonal unit cell parameters are a = 6.9687(1), c = 6.3004(1) angstrom, Z = 3, and space group P6(2)22.
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| 22. |
- Prescott, Eva, et al.
(författare)
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Design and rationale of FLAVOUR : A phase IIa efficacy study of the 5-lipoxygenase activating protein antagonist AZD5718 in patients with recent myocardial infarction
- 2020
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Ingår i: Contemporary Clinical Trials Communications. - : Elsevier BV. - 2451-8654. ; 19
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Tidskriftsartikel (refereegranskat)abstract
- Patients with coronary artery disease remain at increased risk of recurrent life-threatening cardiovascular events even after adequate guideline-based treatment of conventional risk factors, including blood lipid levels. Inflammation is a critical pathway in the pathogenesis of atherosclerosis and is independently associated with risk of recurrent cardiovascular events. Leukotrienes are potent pro-inflammatory and vasoactive mediators synthesized by leukocytes in atherosclerotic lesions. AZD5718 is a novel antagonist of 5-lipoxygenase activating protein that suppresses leukotriene biosynthesis. FLAVOUR is a phase IIa efficacy and safety study of AZD5718 in patients with myocardial infarction 1–4 weeks before randomization. Stenosis of the left anterior descending coronary artery after percutaneous intervention must be <50%, and Thrombolysis In Myocardial Infarction flow grade must be ≥ 2. Enrolled participants receive standard care plus oral AZD5718 200 mg, 50 mg, or placebo once daily for up to 12 weeks (extended from 4 weeks by protocol amendment). The planned sample size is 100 participants randomized to 12 weeks’ treatment. Change in urine leukotriene E4 levels is the primary efficacy outcome. FLAVOUR also aims to evaluate whether AZD5718 can improve coronary microvascular function, as measured by transthoracic colour Doppler-assisted coronary flow velocity reserve. Centrally pretrained study sonographers use standardized protocols and equipment. Additional outcomes include assessment of comprehensive echocardiographic parameters (including coronary flow, global strain, early diastolic strain rate and left ventricular ejection fraction), arterial stiffness, biomarkers, health-related quality of life, and safety. Specific anti-inflammatory therapies may represent novel promising treatments to reduce residual risk in patients with coronary artery disease. By combining primary pharmacodynamic and secondary cardiovascular surrogate efficacy outcomes, FLAVOUR aims to investigate the mechanistic basis and potential benefits of AZD5718 treatment in patients with coronary artery disease.
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| 23. |
- Prescott, Eva, et al.
(författare)
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Safety and efficacy of the 5-lipoxygenase-activating protein inhibitor AZD5718 in patients with recent myocardial infarction: The phase 2a FLAVOUR study.
- 2022
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Ingår i: International journal of cardiology. - : Elsevier BV. - 1874-1754 .- 0167-5273. ; 365, s. 34-40
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Tidskriftsartikel (refereegranskat)abstract
- Leukotrienes are pro-inflammatory vasoactive lipid mediators implicated in the pathophysiology of atherosclerotic cardiovascular disease. We studied the effect of the 5-lipoxygenase-activating protein inhibitor AZD5718 on leukotriene biosynthesis and coronary microvascular function in a single-blind, phase 2a study.Patients 7-28days after myocardial infarction (±ST elevation), with <50% left anterior descending coronary artery stenosis and Thrombolysis in Myocardial Infarction flow grade≥2 after percutaneous coronary intervention, were randomized 2:1:2 to once-daily AZD5718 200mg or 50mg, or placebo, in 4- and 12-week cohorts. Change in urine leukotriene E4 (uLTE4) was the primary endpoint, and coronary flow velocity reserve (CFVR; via echocardiography) was the key secondary endpoint.Of 129 randomized patients, 128 received treatment (200mg, n=52; 50mg, n=25; placebo, n=51). Statistically significant reductions in uLTE4 levels of >80% were observed in both AZD5718 groups versus the placebo group at 4 and 12weeks. No significant changes in CFVR were observed for AZD5718 versus placebo. Adverse events (AEs) occurred in 12/18, 3/6 and 6/13 patients receiving 200mg, 50mg and placebo, respectively, in the 4-week cohort, and in 27/34, 14/19 and 24/38 patients, respectively, in the 12-week cohort. Serious AEs in seven patients receiving AZD5718 and four receiving placebo were not treatment-related, and there were no deaths.In patients with recent myocardial infarction, AZD5718 was well tolerated, and leukotriene biosynthesis was dose-dependently inhibited. No significant changes in CFVR were detected.gov identifier: NCT03317002.
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| 24. |
- Reverté, Sara, et al.
(författare)
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National records of 3000 European bee and hoverfly species : A contribution to pollinator conservation
- 2023
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Ingår i: Insect Conservation and Diversity. - 1752-458X. ; 16:6, s. 758-775
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Tidskriftsartikel (refereegranskat)abstract
- Pollinators play a crucial role in ecosystems globally, ensuring the seed production of most flowering plants. They are threatened by global changes and knowledge of their distribution at the national and continental levels is needed to implement efficient conservation actions, but this knowledge is still fragmented and/or difficult to access. As a step forward, we provide an updated list of around 3000 European bee and hoverfly species, reflecting their current distributional status at the national level (in the form of present, absent, regionally extinct, possibly extinct or non-native). This work was attainable by incorporating both published and unpublished data, as well as knowledge from a large set of taxonomists and ecologists in both groups. After providing the first National species lists for bees and hoverflies for many countries, we examine the current distributional patterns of these species and designate the countries with highest levels of species richness. We also show that many species are recorded in a single European country, highlighting the importance of articulating European and national conservation strategies. Finally, we discuss how the data provided here can be combined with future trait and Red List data to implement research that will further advance pollinator conservation.
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| 25. |
- Rosal Sandberg, Jaime Axel, 1983-
(författare)
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New efficient integral algorithms for quantum chemistry
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The contents of this thesis are centered in the developement of new efficient algorithms for molecular integral evaluation in quantum chemistry, as well as new design and implementation strategies for such algorithms aimed at maximizing their performance and the utilization of modern hardware.This thesis introduces the K4+MIRROR algorithm for 2-electron repulsion integrals, a new ERI integral scheme effective for both segmented and general contraction, which surpasses the performance of all previous ERI analytic algorithms published in the literature. The performance of the K4 kernel contraction schemeis further boosted by the use of some new recurrence relations, CDR/AERR family of recurrences, and the algorithms is further refined for spherical GTOs with the also new SKS method.New prescreening methods for two-electron integrals are also derived, allowing a more consistent methodology for discarding negligible ERI batches. This thesis introduces new techniques useful to pack integrals efficiently and better exploit the underlying modern SIMD or stream processing hardware. These algorithms and methods are implemented in a new library, the Echidna Fock Solver, a hybrid parallelized module for computing Coulomb and Exchange matrices which has been interfaced to the Dalton suite of quantum chemistry programs. Self-Consistent Field and Response Theory calculations in Dalton using the new EFS library are substantially accelerated, also enabling for the first time the use of general contraction basis sets as default basis for extended calculations.The thesis further describes the derivation and implementation of an integral algorithm for evaluating the matrix elements needed for the recently introduced QM/CMM method, for which many of the techniques previously derived are also used, along with a suitable prescreening method for the matrix elements. The implementation is also interfaced to the Dalton quantum chemistry program, and used in production calculations.The last chapter of the thesis is devoted to the derivation of a general analytic solution for type-II Effective Core Potential integrals, arguably one of the most troublesome molecular integrals in quantum chemistry. A new recurrence is introduced for the integrals, and a screening method is presented. Based on these results, a new efficient algorithm for computing type-II ECPs is also described.
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| 26. |
- Ruge, Toralph, et al.
(författare)
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Circulating endostatin as a risk factor for cardiovascular events in patients with stable coronary heart disease : A CLARICOR trial sub-study
- 2019
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Ingår i: Atherosclerosis. - : Elsevier BV. - 0021-9150 .- 1879-1484. ; 284, s. 202-208
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND AIMS: Raised levels of serum endostatin, a biologically active fragment of collagen XVIII, have been observed in patients with ischemic heart disease but association with incident cardiovascular events in patients with stable coronary heart disease is uncertain.METHODS: The CLARICOR-trial is a randomized, placebo-controlled trial of stable coronary heart disease patients evaluating 14-day treatment with clarithromycin. The primary outcome was a composite of acute myocardial infarction, unstable angina pectoris, cerebrovascular disease or all-cause mortality. In the present sub-study using 10-year follow-up data, we investigated associations between serum endostatin at entry (randomization) and the composite outcome and its components during follow-up. The placebo group was used as discovery sample (1204 events, n = 1998) and the clarithromycin-treated group as replication sample (1220 events, n = 1979).RESULTS: In Cox regression models adjusting for cardiovascular risk factors, glomerular filtration rate, and current pharmacological treatment, higher serum endostatin was associated with an increased risk of the composite outcome in the discovery sample (hazard ratio per standard deviation increase 1.11, 95% CI 1.03-1.19, p = 0.004), but slightly weaker and not statistically significant in the replication sample (hazard ratio 1.06, 95% CI 1.00-1.14, p = 0.06). In contrast, strong and consistent associations were found between endostatin and cardiovascular and all-cause mortality in all multivariable models and sub-samples. Addition of endostatin to a model with established cardiovascular risk factors provided no substantial improvement of risk prediction (<1%).CONCLUSIONS: Raised levels of serum endostatin might be associated with cardiovascular events in patients with stable coronary heart disease. The clinical utility of endostatin measurements remains to be established.
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| 27. |
- van der Valk, Tom, et al.
(författare)
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Comparative genomic analyses provide new insights into evolutionary history and conservation genomics of gorillas
- 2024
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Ingår i: BMC Ecology and Evolution. - : BioMed Central (BMC). - 2730-7182. ; 24:1
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Tidskriftsartikel (refereegranskat)abstract
- Genome sequencing is a powerful tool to understand species evolutionary history, uncover genes under selection, which could be informative of local adaptation, and infer measures of genetic diversity, inbreeding and mutational load that could be used to inform conservation efforts. Gorillas, critically endangered primates, have received considerable attention and with the recently sequenced Bwindi mountain gorilla population, genomic data is now available from all gorilla subspecies and both mountain gorilla populations. Here, we reanalysed this rich dataset with a focus on evolutionary history, local adaptation and genomic parameters relevant for conservation. We estimate a recent split between western and eastern gorillas of 150,000-180,000 years ago, with gene flow around 20,000 years ago, primarily between the Cross River and Grauer's gorilla subspecies. This gene flow event likely obscures evolutionary relationships within eastern gorillas: after excluding putatively introgressed genomic regions, we uncover a sister relationship between Virunga mountain gorillas and Grauer's gorillas to the exclusion of Bwindi mountain gorillas. This makes mountain gorillas paraphyletic. Eastern gorillas are less genetically diverse and more inbred than western gorillas, yet we detected lower genetic load in the eastern species. Analyses of indels fit remarkably well with differences in genetic diversity across gorilla taxa as recovered with nucleotide diversity measures. We also identified genes under selection and unique gene variants specific for each gorilla subspecies, encoding, among others, traits involved in immunity, diet, muscular development, hair morphology and behavior. The presence of this functional variation suggests that the subspecies may be locally adapted. In conclusion, using extensive genomic resources we provide a comprehensive overview of gorilla genomic diversity, including a so-far understudied Bwindi mountain gorilla population, identify putative genes involved in local adaptation, and detect population-specific gene flow across gorilla species.
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| 28. |
- Wester, Axel, et al.
(författare)
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Impact of Baseline Anemia in Patients With Acute Coronary Syndromes Undergoing Percutaneous Coronary Intervention : A Prespecified Analysis From the VALIDATE-SWEDEHEART Trial
- 2019
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Ingår i: Journal of the American Heart Association. - 2047-9980. ; 8:16, s. 012741-012741
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Tidskriftsartikel (refereegranskat)abstract
- Background The impact of baseline anemia in a contemporary acute coronary syndrome (ACS) population undergoing percutaneous coronary intervention in the era of predominant radial artery access, potent P2Y12 inhibition, and rare use of glycoprotein IIb/IIIa inhibitors has not been adequately studied. Methods and Results ACS patients who underwent percutaneous coronary intervention between 2014 and 2016 in the VALIDATE-SWEDEHEART (Bivalirudin Versus Heparin in ST-Segment and Non-ST-Segment Elevation Myocardial Infarction in Patients on Modern Antiplatelet Therapy in the Swedish Web System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies Registry) trial without missing values for hemoglobin were included (n=5482). Mortality, myocardial reinfarction, and major bleeding at 180 days were assessed using Cox regression models and propensity score matching. All studied comorbidities were more common in ACS patients who had anemia (n=792). ACS patients with anemia had higher rates of 180-day mortality (6.9% versus 2.1%; hazard ratio, 1.9; 95% CI, 1.3-2.7; P<0.001), myocardial reinfarction (4.3% versus 1.9%; hazard ratio, 1.7; 95% CI, 1.1-2.7; P=0.013), and major bleeding (13.4% versus 8.2%; hazard ratio, 1.3; 95% CI, 1.0-1.6; P=0.041). The results were most evident in patients with a hemoglobin value <100 g/L, who had a nearly 10 times higher mortality rate. Conclusions Baseline anemia in ACS patients undergoing percutaneous coronary intervention, treated according to current practice including routine radial artery access, constitutes a high-risk feature for both ischemic events, bleeding events, and mortality. A multidisciplinary approach is warranted to maximize benefit and minimize patient risk. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT02311231.
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| 29. |
- Wuopio, Jonas, et al.
(författare)
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Cathepsin B and S as markers for cardiovascular risk and all-cause mortality in patients with stable coronary heart disease during 10 years : a CLARICOR trial sub-study.
- 2018
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Ingår i: Atherosclerosis. - : Elsevier BV. - 0021-9150 .- 1879-1484. ; 278, s. 97-102
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND AIMS: The lysosomal cysteine proteases cathepsin B and S have been implicated in the atherosclerotic process. The present paper investigates the association between serum levels of cathepsin B and S and cardiovascular events and mortality in patients with stable coronary heart disease.METHODS: The CLARICOR trial is a randomised, placebo-controlled trial investigating the effect of clarithromycin versus placebo in patients with stable coronary heart disease. The outcome was time to either a cardiovascular event or all-cause mortality. The placebo group was used as discovery sample and the clarithromycin group as replication sample: n = 1998, n = 1979; mean age (years) 65, 65; 31%, 30% women; follow-up for 10 years; number of composite outcomes n = 1204, n = 1220; respectively. We used a pre-defined multivariable Cox regression model adjusting for inflammation, established cardiovascular risk factors, kidney function, and use of cardiovascular drugs.RESULTS: Cathepsin B was associated with an increased risk of the composite outcome in both samples after multivariable adjustment (discovery: multivariable ratio (HR) per standard deviation increase 1.12, 95% confidence interval (CI) 1.05-1.19, p < 0.001, replication; HR 1.14, 95% CI 1.07-1.21, p < 0.001). There was no significant association between cathepsin S and the composite outcome in either the discovery or replication sample after multivariable adjustment (p>0.45). Secondary analyses suggest that cathepsin B was predominantly associated with mortality rather than specific cardiovascular events.CONCLUSIONS: Cathepsin B, but not serum cathepsin S, was associated with an increased risk of cardiovascular events in patients with stable coronary heart disease. The clinical implications of our findings remain to be established.
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