| 1. |
- Kanai, M, et al.
(författare)
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- 2023
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swepub:Mat__t
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| 2. |
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| 3. |
- Fenstermacher, M.E., et al.
(författare)
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DIII-D research advancing the physics basis for optimizing the tokamak approach to fusion energy
- 2022
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Ingår i: Nuclear Fusion. - : IOP Publishing. - 0029-5515 .- 1741-4326. ; 62:4
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Tidskriftsartikel (refereegranskat)abstract
- DIII-D physics research addresses critical challenges for the operation of ITER and the next generation of fusion energy devices. This is done through a focus on innovations to provide solutions for high performance long pulse operation, coupled with fundamental plasma physics understanding and model validation, to drive scenario development by integrating high performance core and boundary plasmas. Substantial increases in off-axis current drive efficiency from an innovative top launch system for EC power, and in pressure broadening for Alfven eigenmode control from a co-/counter-I p steerable off-axis neutral beam, all improve the prospects for optimization of future long pulse/steady state high performance tokamak operation. Fundamental studies into the modes that drive the evolution of the pedestal pressure profile and electron vs ion heat flux validate predictive models of pedestal recovery after ELMs. Understanding the physics mechanisms of ELM control and density pumpout by 3D magnetic perturbation fields leads to confident predictions for ITER and future devices. Validated modeling of high-Z shattered pellet injection for disruption mitigation, runaway electron dissipation, and techniques for disruption prediction and avoidance including machine learning, give confidence in handling disruptivity for future devices. For the non-nuclear phase of ITER, two actuators are identified to lower the L-H threshold power in hydrogen plasmas. With this physics understanding and suite of capabilities, a high poloidal beta optimized-core scenario with an internal transport barrier that projects nearly to Q = 10 in ITER at ∼8 MA was coupled to a detached divertor, and a near super H-mode optimized-pedestal scenario with co-I p beam injection was coupled to a radiative divertor. The hybrid core scenario was achieved directly, without the need for anomalous current diffusion, using off-axis current drive actuators. Also, a controller to assess proximity to stability limits and regulate β N in the ITER baseline scenario, based on plasma response to probing 3D fields, was demonstrated. Finally, innovative tokamak operation using a negative triangularity shape showed many attractive features for future pilot plant operation.
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| 4. |
- Ramdas, S., et al.
(författare)
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A multi-layer functional genomic analysis to understand noncoding genetic variation in lipids
- 2022
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 109:8, s. 1366-1387
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Tidskriftsartikel (refereegranskat)abstract
- A major challenge of genome-wide association studies (GWASs) is to translate phenotypic associations into biological insights. Here, we integrate a large GWAS on blood lipids involving 1.6 million individuals from five ancestries with a wide array of functional genomic datasets to discover regulatory mechanisms underlying lipid associations. We first prioritize lipid-associated genes with expression quantitative trait locus (eQTL) colocalizations and then add chromatin interaction data to narrow the search for functional genes. Polygenic enrichment analysis across 697 annotations from a host of tissues and cell types confirms the central role of the liver in lipid levels and highlights the selective enrichment of adipose-specific chromatin marks in high-density lipoprotein cholesterol and triglycerides. Overlapping transcription factor (TF) binding sites with lipid-associated loci identifies TFs relevant in lipid biology. In addition, we present an integrative framework to prioritize causal variants at GWAS loci, producing a comprehensive list of candidate causal genes and variants with multiple layers of functional evidence. We highlight two of the prioritized genes, CREBRF and RRBP1, which show convergent evidence across functional datasets supporting their roles in lipid biology.
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| 5. |
- Reifarth, R., et al.
(författare)
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Nuclear astrophysics with radioactive ions at FAIR
- 2016
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Ingår i: Journal of Physics: Conference Series. - : IOP Publishing. - 1742-6588 .- 1742-6596. ; 665:1
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Konferensbidrag (refereegranskat)abstract
- The nucleosynthesis of elements beyond iron is dominated by neutron captures in the s and r processes. However, 32 stable, proton-rich isotopes cannot be formed during those processes, because they are shielded from the s-process flow and r-process beta-decay chains. These nuclei are attributed to the p and rp process. For all those processes, current research in nuclear astrophysics addresses the need for more precise reaction data involving radioactive isotopes. Depending on the particular reaction, direct or inverse kinematics, forward or time-reversed direction are investigated to determine or at least to constrain the desired reaction cross sections. The Facility for Antiproton and Ion Research (FAIR) will offer unique, unprecedented opportunities to investigate many of the important reactions. The high yield of radioactive isotopes, even far away from the valley of stability, allows the investigation of isotopes involved in processes as exotic as the r or rp processes.
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| 11. |
- Kanoni, Stavroula, et al.
(författare)
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Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.
- 2022
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Ingår i: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N=1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism.Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.
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| 12. |
- Zheng, TH, et al.
(författare)
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Genome-wide analysis of 944 133 individuals provides insights into the etiology of haemorrhoidal disease
- 2021
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Ingår i: Gut. - : BMJ. - 1468-3288 .- 0017-5749. ; 70:8, s. 1538-1549
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Tidskriftsartikel (refereegranskat)abstract
- Haemorrhoidal disease (HEM) affects a large and silently suffering fraction of the population but its aetiology, including suspected genetic predisposition, is poorly understood. We report the first genome-wide association study (GWAS) meta-analysis to identify genetic risk factors for HEM to date.DesignWe conducted a GWAS meta-analysis of 218 920 patients with HEM and 725 213 controls of European ancestry. Using GWAS summary statistics, we performed multiple genetic correlation analyses between HEM and other traits as well as calculated HEM polygenic risk scores (PRS) and evaluated their translational potential in independent datasets. Using functional annotation of GWAS results, we identified HEM candidate genes, which differential expression and coexpression in HEM tissues were evaluated employing RNA-seq analyses. The localisation of expressed proteins at selected loci was investigated by immunohistochemistry.ResultsWe demonstrate modest heritability and genetic correlation of HEM with several other diseases from the GI, neuroaffective and cardiovascular domains. HEM PRS validated in 180 435 individuals from independent datasets allowed the identification of those at risk and correlated with younger age of onset and recurrent surgery. We identified 102 independent HEM risk loci harbouring genes whose expression is enriched in blood vessels and GI tissues, and in pathways associated with smooth muscles, epithelial and endothelial development and morphogenesis. Network transcriptomic analyses highlighted HEM gene coexpression modules that are relevant to the development and integrity of the musculoskeletal and epidermal systems, and the organisation of the extracellular matrix.ConclusionHEM has a genetic component that predisposes to smooth muscle, epithelial and connective tissue dysfunction.
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| 13. |
- Schaper, S. J., et al.
(författare)
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Revealing the growth of copper on polystyrene- : Block -poly(ethylene oxide) diblock copolymer thin films with in situ GISAXS
- 2021
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Ingår i: Nanoscale. - : Royal Society of Chemistry (RSC). - 2040-3364 .- 2040-3372. ; 13:23, s. 10555-10565
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Tidskriftsartikel (refereegranskat)abstract
- Copper (Cu) as an excellent electrical conductor and the amphiphilic diblock copolymer polystyrene-block-poly(ethylene oxide) (PS-b-PEO) as a polymer electrolyte and ionic conductor can be combined with an active material in composite electrodes for polymer lithium-ion batteries (LIBs). As interfaces are a key issue in LIBs, sputter deposition of Cu contacts on PS-b-PEO thin films with high PEO fraction is investigated with in situ grazing-incidence small-angle X-ray scattering (GISAXS) to follow the formation of the Cu layer in real-time. We observe a hierarchical morphology of Cu clusters building larger Cu agglomerates. Two characteristic distances corresponding to the PS-b-PEO microphase separation and the Cu clusters are determined. A selective agglomeration of Cu clusters on the PS domains explains the origin of the persisting hierarchical morphology of the Cu layer even after a complete surface coverage is reached. The spheroidal shape of the Cu clusters growing within the first few nanometers of sputter deposition causes a highly porous Cu-polymer interface. Four growth stages are distinguished corresponding to different kinetics of the cluster growth of Cu on PS-b-PEO thin films: (I) nucleation, (II) diffusion-driven growth, (III) adsorption-driven growth, and (IV) grain growth of Cu clusters. Percolation is reached at an effective Cu layer thickness of 5.75 nm.
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| 15. |
- Contessotto, P., et al.
(författare)
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Reproducing extracellular matrix adverse remodelling of non-ST myocardial infarction in a large animal model
- 2023
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- The rising incidence of non-ST-segment elevation myocardial infarction (NSTEMI) and associated long-term high mortality constitutes an urgent clinical issue. Unfortunately, the study of possible interventions to treat this pathology lacks a reproducible pre-clinical model. Indeed, currently adopted small and large animal models of MI mimic only full-thickness, ST-segment-elevation (STEMI) infarcts, and hence cater only for an investigation into therapeutics and interventions directed at this subset of MI. Thus, we develop an ovine model of NSTEMI by ligating the myocardial muscle at precise intervals parallel to the left anterior descending coronary artery. Upon histological and functional investigation to validate the proposed model and comparison with STEMI full ligation model, RNA-seq and proteomics show the distinctive features of post-NSTEMI tissue remodelling. Transcriptome and proteome-derived pathway analyses at acute (7 days) and late (28 days) post-NSTEMI pinpoint specific alterations in cardiac post-ischaemic extracellular matrix. Together with the rise of well-known markers of inflammation and fibrosis, NSTEMI ischaemic regions show distinctive patterns of complex galactosylated and sialylated N-glycans in cellular membranes and extracellular matrix. Identifying such changes in molecular moieties accessible to infusible and intra-myocardial injectable drugs sheds light on developing targeted pharmacological solutions to contrast adverse fibrotic remodelling. The study of the pathophysiology and possible interventions for non-ST-segment elevation myocardial infarction is hindered by the lack of a reproducible pre-clinical model. Here, authors develop an ovine model to reproduce post-ischemic remodeling in non-ST myocardial infarction and reveal distinct complex sugar moieties in cellular membranes and extracellular matrix patterns in infarcted tissue.
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| 16. |
- Pandit, R., et al.
(författare)
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An overview of the statistical properties of two-dimensional turbulence in fluids with particles, conducting fluids, fluids with polymer additives, binary-fluid mixtures, and superfluids
- 2017
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Ingår i: Physics of fluids. - : American Institute of Physics (AIP). - 1070-6631 .- 1089-7666. ; 29:11
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Tidskriftsartikel (refereegranskat)abstract
- We present an overview of the statistical properties of turbulence in two-dimensional (2D) fluids. After a brief recapitulation of well-known results for statistically homogeneous and isotropic 2D fluid turbulence, we give an overview of recent progress in this field for such 2D turbulence in conducting fluids, fluids with polymer additives, binary-fluid mixtures, and superfluids; we also discuss the statistical properties of particles advected by 2D turbulent fluids.
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| 17. |
- Schwieler, J H, et al.
(författare)
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Reentry in an accessory atrioventricular pathway as a trigger for atrial fibrillation initiation in manifest Wolff-Parkinson-White syndrome: A matter of reflection?
- 2008
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Ingår i: Heart rhythm : the official journal of the Heart Rhythm Society. - : Elsevier BV. - 1556-3871 .- 1547-5271. ; 5:9, s. 1238-47
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Patients with an accessory pathway (AP) have an increased propensity to develop atrial fibrillation (AF), but the mechanism is unknown. OBJECTIVE: The purpose of this study was to identify crucial risk factors and to test the hypothesis that reflection and/or microreentry of atrial impulses propagating into the AP triggers AF. METHODS: Five hundred thirty-four patients successfully treated with radiofrequency ablation of AP at two university hospitals were evaluated. Patients were separated into those with concealed vs those with manifest AP in terms of their propensity to develop AF. To investigate AF triggering mechanisms, linear and branched two-dimensional models of atrium-to-ventricle propagation across a heterogeneous 1 x 6 AP using human ionic kinetics were simulated. RESULTS: A history of AF was twice as common in patients with manifest AP vs concealed AP irrespective of AP location. AF was more likely to occur in older males and in patients with larger atria. There was no correlation between AF history and AP refractory measures. However, the electrophysiologic properties of APs seemed to fulfill the prerequisites for reflection and/or microreentry of atrially initiated impulses. In the linear AP model, repetitive atrial stimulation resulted in progressively larger delay of atrium-to-ventricle propagation across the passive segment. Eventually, sufficient time for repolarization of the atrial segment allowed for reflection of an impulse that activated the entire atrium and by wavefront-wavetail interaction with a new atrial stimulus AF reentry was initiated. Simulations using the branched model showed that microreentry at the ventricular insertion of the AP could also initiate AF via retrograde atrial activation as a result of unidirectional block at the AP-ventricle junction. CONCLUSION: Propensity for AF in patients with an AP is strongly related to preexcitation, larger atria, male gender, and older age. Reflection and microreentry at the AP may be important for AF initiation in patients with manifest (preexcited) Wolff-Parkinson-White syndrome. Similar mechanisms also may trigger AF in patients without an AP.
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