| 1. |
- Ruilope, LM, et al.
(författare)
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Design and Baseline Characteristics of the Finerenone in Reducing Cardiovascular Mortality and Morbidity in Diabetic Kidney Disease Trial
- 2019
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Ingår i: American journal of nephrology. - : S. Karger AG. - 1421-9670 .- 0250-8095. ; 50:5, s. 345-356
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Tidskriftsartikel (refereegranskat)abstract
- <b><i>Background:</i></b> Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. <b><i>Patients and</i></b> <b><i>Methods:</i></b> The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate ≥25 mL/min/1.73 m<sup>2</sup> and albuminuria (urinary albumin-to-creatinine ratio ≥30 to ≤5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level α = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. <b><i>Conclusions:</i></b> FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049.
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| 2. |
- Abdellaoui, G., et al.
(författare)
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Meteor studies in the framework of the JEM-EUSO program
- 2017
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Ingår i: Planetary and Space Science. - : Elsevier. - 0032-0633 .- 1873-5088. ; 143, s. 245-255
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Tidskriftsartikel (refereegranskat)abstract
- We summarize the state of the art of a program of UV observations from space of meteor phenomena, a secondary objective of the JEM-EUSO international collaboration. Our preliminary analysis indicates that JEM-EUSO, taking advantage of its large FOV and good sensitivity, should be able to detect meteors down to absolute magnitude close to 7. This means that JEM-EUSO should be able to record a statistically significant flux of meteors, including both sporadic ones, and events produced by different meteor streams. Being unaffected by adverse weather conditions, JEM-EUSO can also be a very important facility for the detection of bright meteors and fireballs, as these events can be detected even in conditions of very high sky background. In the case of bright events, moreover, exhibiting some persistence of the meteor train, preliminary simulations show that it should be possible to exploit the motion of the ISS itself and derive at least a rough 3D reconstruction of the meteor trajectory. Moreover, the observing strategy developed to detect meteors may also be applied to the detection of nuclearites, exotic particles whose existence has been suggested by some theoretical investigations. Nuclearites are expected to move at higher velocities than meteoroids, and to exhibit a wider range of possible trajectories, including particles moving upward after crossing the Earth. Some pilot studies, including the approved Mini-EUSO mission, a precursor of JEM-EUSO, are currently operational or in preparation. We are doing simulations to assess the performance of Mini-EUSO for meteor studies, while a few meteor events have been already detected using the ground-based facility EUSO-TA.
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| 3. |
- Abdellaoui, G., et al.
(författare)
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First observations of speed of light tracks by a fluorescence detector looking down on the atmosphere
- 2018
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Ingår i: Journal of Instrumentation. - : IOP PUBLISHING LTD. - 1748-0221. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- EUSO-Balloon is a pathfinder mission for the Extreme Universe Space Observatory onboard the Japanese Experiment Module (JEM-EUSO). It was launched on the moonless night of the 25(th) of August 2014 from Timmins, Canada. The flight ended successfully after maintaining the target altitude of 38 km for five hours. One part of the mission was a 2.5 hour underflight using a helicopter equipped with three UV light sources (LED, xenon flasher and laser) to perform an inflight calibration and examine the detectors capability to measure tracks moving at the speed of light. We describe the helicopter laser system and details of the underflight as well as how the laser tracks were recorded and found in the data. These are the first recorded laser tracks measured from a fluorescence detector looking down on the atmosphere. Finally, we present a first reconstruction of the direction of the laser tracks relative to the detector.
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| 4. |
- Noguchi, S, et al.
(författare)
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FANTOM5 CAGE profiles of human and mouse samples
- 2017
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Ingår i: Scientific data. - : Springer Science and Business Media LLC. - 2052-4463. ; 4, s. 170112-
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Tidskriftsartikel (refereegranskat)abstract
- In the FANTOM5 project, transcription initiation events across the human and mouse genomes were mapped at a single base-pair resolution and their frequencies were monitored by CAGE (Cap Analysis of Gene Expression) coupled with single-molecule sequencing. Approximately three thousands of samples, consisting of a variety of primary cells, tissues, cell lines, and time series samples during cell activation and development, were subjected to a uniform pipeline of CAGE data production. The analysis pipeline started by measuring RNA extracts to assess their quality, and continued to CAGE library production by using a robotic or a manual workflow, single molecule sequencing, and computational processing to generate frequencies of transcription initiation. Resulting data represents the consequence of transcriptional regulation in each analyzed state of mammalian cells. Non-overlapping peaks over the CAGE profiles, approximately 200,000 and 150,000 peaks for the human and mouse genomes, were identified and annotated to provide precise location of known promoters as well as novel ones, and to quantify their activities.
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| 5. |
- Kato, Norihiro, et al.
(författare)
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Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation
- 2015
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 47:11, s. 1282-1293
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Tidskriftsartikel (refereegranskat)abstract
- We carried out a trans-ancestry genome-wide association and replication study of blood pressure phenotypes among up to 320,251 individuals of East Asian, European and South Asian ancestry. We find genetic variants at 12 new loci to be associated with blood pressure (P = 3.9 × 10−11 to 5.0 × 10−21). The sentinel blood pressure SNPs are enriched for association with DNA methylation at multiple nearby CpG sites, suggesting that, at some of the loci identified, DNA methylation may lie on the regulatory pathway linking sequence variation to blood pressure. The sentinel SNPs at the 12 new loci point to genes involved in vascular smooth muscle (IGFBP3, KCNK3, PDE3A and PRDM6) and renal (ARHGAP24, OSR1, SLC22A7 and TBX2) function. The new and known genetic variants predict increased left ventricular mass, circulating levels of NT-proBNP, and cardiovascular and all-cause mortality (P = 0.04 to 8.6 × 10−6). Our results provide new evidence for the role of DNA methylation in blood pressure regulation.
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| 6. |
- Kraehling, J. R., et al.
(författare)
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Genome-wide RNAi screen reveals ALK1 mediates LDL uptake and transcytosis in endothelial cells
- 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
- In humans and animals lacking functional LDL receptor (LDLR), LDL from plasma still readily traverses the endothelium. To identify the pathways of LDL uptake, a genome-wide RNAi screen was performed in endothelial cells and cross-referenced with GWAS-data sets. Here we show that the activin-like kinase 1 (ALK1) mediates LDL uptake into endothelial cells. ALK1 binds LDL with lower affinity than LDLR and saturates only at hypercholesterolemic concentrations. ALK1 mediates uptake of LDL into endothelial cells via an unusual endocytic pathway that diverts the ligand from lysosomal degradation and promotes LDL transcytosis. The endothelium-specific genetic ablation of Alk1 in Ldlr-KO animals leads to less LDL uptake into the aortic endothelium, showing its physiological role in endothelial lipoprotein metabolism. In summary, identification of pathways mediating LDLR-independent uptake of LDL may provide unique opportunities to block the initiation of LDL accumulation in the vessel wall or augment hepatic LDLR-dependent clearance of LDL. © The Author(s) 2016.
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| 7. |
- Sassa, Yasmine, et al.
(författare)
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The metallic quasi-1D spin-density-wave compound NaV2O4 studied by angle-resolved photoelectron spectroscopy
- 2018
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Ingår i: Journal of Electron Spectroscopy and Related Phenomena. - : ELSEVIER SCIENCE BV. - 0368-2048 .- 1873-2526. ; 224, s. 79-83
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Tidskriftsartikel (refereegranskat)abstract
- Angle-resolved photoelectron spectroscopy has been used to follow the valence band and near Fermi edge electronic band structure in the quasi-1D compound NaV2O4. In this current study we have acquired the very first high-quality, high-resolution ARPES data from this material. Our data clearly reveal two distinct dispersive bands that cross the Fermi level at different k(F). This is a clear signature that the electronic properties of this material is affected by the presence of a mixed valence state on the different vanadium chains and possibly also the low-temperature magnetic spin order.
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| 8. |
- Sugiyama, J., et al.
(författare)
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Desorption reaction in MgH 2 studied with in situ μ + SR
- 2019
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Ingår i: Sustainable Energy & Fuels. - : Royal Society of Chemistry. - 2398-4902. ; 3:4, s. 956-964
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Tidskriftsartikel (refereegranskat)abstract
- In order to study the mechanism determining the desorption temperature (T d ) of hydrogen storage materials, we have measured positive muon spin rotation and relaxation (μ + SR) in MgH 2 over a wide temperature range including its T d . The pressure in the sample cell due to desorbed H 2 was measured in parallel with the μ + SR measurements under static conditions. Such in situ μ + SR measurements revealed that hydrogen starts to diffuse in MgH 2 well below T d . This indicates the important role of hydrogen diffusion in accelerating the desorption reaction by removing the reaction product, i.e. H 2 , from the reaction system.
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| 9. |
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| 10. |
- Bowman, John L, et al.
(författare)
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Insights into Land Plant Evolution Garnered from the Marchantia polymorpha Genome
- 2017
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Ingår i: Cell. - : Elsevier BV. - 0092-8674 .- 1097-4172. ; 171:2, s. 287-304.15
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Tidskriftsartikel (refereegranskat)abstract
- The evolution of land flora transformed the terrestrial environment. Land plants evolved from an ancestral charophycean alga from which they inherited developmental, biochemical, and cell biological attributes. Additional biochemical and physiological adaptations to land, and a life cycle with an alternation between multicellular haploid and diploid generations that facilitated efficient dispersal of desiccation tolerant spores, evolved in the ancestral land plant. We analyzed the genome of the liverwort Marchantia polymorpha, a member of a basal land plant lineage. Relative to charophycean algae, land plant genomes are characterized by genes encoding novel biochemical pathways, new phytohormone signaling pathways (notably auxin), expanded repertoires of signaling pathways, and increased diversity in some transcription factor families. Compared with other sequenced land plants, M. polymorpha exhibits low genetic redundancy in most regulatory pathways, with this portion of its genome resembling that predicted for the ancestral land plant. PAPERCLIP.
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| 11. |
- Forslund, Ola Kenji, et al.
(författare)
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Magnetic phase diagram of K 2 Cr 8 O 16 clarified by high-pressure muon spin spectroscopy
- 2019
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- The K 2 Cr 8 O 16 compound belongs to a series of quasi-1D compounds with intriguing magnetic properties that are stabilized through a high-pressure synthesis technique. In this study, a muon spin rotation, relaxation and resonance (μ + SR) technique is used to investigate the pressure dependent magnetic properties up to 25 kbar. μ + SR allows for measurements in true zero applied field and hereby access the true intrinsic material properties. As a result, a refined temperature/pressure phase diagram is presented revealing a novel low temperature/high pressure (p C1 = 21 kbar) transition from a ferromagnetic insulating to a high-pressure antiferromagnetic insulator. Finally, the current study also indicates the possible presence of a quantum critical point at p C2 ~ 33 kbar where the magnetic order in K 2 Cr 8 O 16 is expected to be fully suppressed even at T = 0 K.
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| 12. |
- Guo, Yingying, et al.
(författare)
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Advancing Predictions of Tissue and Intracellular Drug Concentrations Using In Vitro, Imaging and Physiologically Based Pharmacokinetic Modeling Approaches
- 2018
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Ingår i: Clinical Pharmacology and Therapeutics. - : John Wiley & Sons. - 0009-9236 .- 1532-6535. ; 104:5, s. 865-889
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Forskningsöversikt (refereegranskat)abstract
- This white paper examines recent progress, applications, and challenges in predicting unbound and total tissue and intra/subcellular drug concentrations using in vitro and preclinical models, imaging techniques, and physiologically based pharmacokinetic (PBPK) modeling. Published examples, regulatory submissions, and case studies illustrate the application of different types of data in drug development to support modeling and decision making for compounds with transporter-mediated disposition, and likely disconnects between tissue and systemic drug exposure. The goals of this article are to illustrate current best practices and outline practical strategies for selecting appropriate in vitro and in vivo experimental methods to estimate or predict tissue and plasma concentrations, and to use these data in the application of PBPK modeling for human pharmacokinetic (PK), efficacy, and safety assessment in drug development.
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| 13. |
- Nozaki, Hiroshi, et al.
(författare)
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Magnetic structure for NaCr2O4 analyzed by neutron diffraction and muon spin-rotation
- 2018
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Ingår i: Physica. B, Condensed matter. - : ELSEVIER SCIENCE BV. - 0921-4526 .- 1873-2135. ; 551, s. 137-141
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Tidskriftsartikel (refereegranskat)abstract
- We have investigated the magnetic ground state of a novel one-dimensional compound, NaCr2O4, in which Cr2O4 double chains, i.e. zig-zag chains are aligned parallel to the b-axis, by means of both muon-spin rotation and relaxation (mu+SR) and neutron diffraction (ND) measurements. The mu+SR results reveal the formation of static antiferromagnetic order below Neel temperature (T-N = 124 K). The ND measurements also demonstrate the appearance of magnetic Bragg peaks with the propagation vector (k) over right arrow = (1, 0, 1) below T-N. Combined analyses of the mu+SR and ND data clarify that the Cr moments in each zig-zag chain are aligned ferromagnetically along the c-axis, whereas antiferromagnetically along the alpha-axis between the adjacent zig-zag chains.
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| 14. |
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| 15. |
- Sugiyama, Jun, et al.
(författare)
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Magnetic ground state of novel zigzag chain compounds, NaCr2O4 and Ca1-xNaxCr2O4, determined with muons and neutrons
- 2015
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Ingår i: 20TH INTERNATIONAL CONFERENCE ON MAGNETISM, ICM 2015. - : Elsevier. ; , s. 868-875
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Konferensbidrag (refereegranskat)abstract
- The magnetic nature of a novel one-dimensional compound NaCr2O4 with zigzag CrO2 chains has been studied by muon spin rotation and relaxation (mu+SR) and neutron diffraction (ND). It is found that NaCr2O4 undergoes an antiferromagnetic transition at T-N = 125 K, below which the Cr moments in each zigzag chain align ferromagnetically along the c-axis but antiferromagnetically along the a-axis between adjacent zigzag chains. For the solid solution system Ca1-xNaxCr2O4, mu+SR measurements reveal the evolution of a complex magnetic order with increasing Ca content (1 - x), which finally enters into an incommensurate AF ordered state below T-N = 21 for CaCr2O4.
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| 16. |
- Sugiyama, Jun, et al.
(författare)
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Magnetic phases in Sr1-xCaxCo2P2 studied by mu+SR
- 2015
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Ingår i: 20TH INTERNATIONAL CONFERENCE ON MAGNETISM, ICM 2015. - : Elsevier. ; , s. 426-434
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Konferensbidrag (refereegranskat)abstract
- In order to elucidate the dependence of the magnetic ground state on the Ca content (x) in Sr1-xCaxCo2P2 (0 <= x <= 1, ThCr2Si2-type structure), we have performed muon spin rotation and relaxation (mu+SR) experiments on Sr1-xCaxCo2P2 powder samples mainly in a zero applied field. The end member compound, SrCo2P2, is found to be paramagnetic down to 19 mK. As x increases, such a paramagnetic ground state is observed down to 1.8 K until x = 0.45. Then, as x increases further, a short-range antiferromagnetic (AF) ordered phase appears at low temperatures for 0.48 <= x <= 0.75, and finally, a long-range AF ordered phase is stabilized for x > 0.75. The internal magnetic field of the other end member compound, CaCo2P2, is well consistent with that of the A-type AF order state, which was proposed from neutron scattering experiments. The phase diagram determined with mu+SR is different from that proposed by macroscopic measurements. For an isostructural compound, LaCo2P2, static magnetic order is found to be formed below similar to 130 K.
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| 17. |
- Sugiyama, Jun, et al.
(författare)
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Magnetism of the A-site ordered perovskites CaCu3Cr4O12 and LaCu3Cr4O12
- 2018
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Ingår i: Physical Review B. - : AMER PHYSICAL SOC. - 2469-9950 .- 2469-9969. ; 97:2
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Tidskriftsartikel (refereegranskat)abstract
- The microscopic magnetic nature of the A-site ordered chromium perovskites CaCu3Cr4O12 and LaCu3Cr4O12 and their solid-solution system, Ca1-x LaxCu3Cr4O12, with x = 0.2, 0.4, and 0.8, has been studied with muon spin rotation and relaxation (mu+SR) measurements down to 2 K using a powder sample. For CaCu3Cr4O12, mu+SR revealed the formation of static antiferromagnetic (AF) order below 122 K (=T-N), although magnetization measurements showed a very small change at T-N. Analyses of the internal magnetic field H-int at the muon sites, predicted with first-principles calculations, suggested G-type AF order as a ground state. For LaCu3Cr4O12 with T-N = 225 K, mu+SR also supported the presence of aG-type AF ordered state, which was recently proposed based on neutron diffraction measurements. However, the ordered Cr moments were found to change the direction at around 10 K. For Ca1-xLaxCu3Cr4O12, both T-N and H-int at 2 K increase monotonically with x.
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| 18. |
- Sugiyama, Jun, et al.
(författare)
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Variation of magnetic ground state of Sr1-xCaxCo2P2 determined with mu(+) SR
- 2015
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Ingår i: Physical Review B. Condensed Matter and Materials Physics. - 1098-0121 .- 1550-235X. ; 91:14
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Tidskriftsartikel (refereegranskat)abstract
- In order to study the variation of a microscopic internal magnetic field with the Ca content (x), we have systematically measured muon-spin rotation and relaxation (mu+SR) spectra for Sr1-xCaxCo2P2 (0 <= x <= 1) powder samples mainly in a zero external field. As x increases from 0, a Pauli-paramagnetic phase is observed even at the lowest T measured (1.8 K) until x = 0.45; then, a short-range antiferromagnetic (AF) ordered phase appears for 0.48 <= x <= 0.75, and finally a long-range AF ordered phase is stabilized for x >= 0.75. The evolution of the magnetic order is connected to the shrinking of the c-axis length as a function of x, which naturally enhances the AF interaction between the two adjacent Co planes.
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