| 1. |
- Ruilope, LM, et al.
(author)
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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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In: American journal of nephrology. - : S. Karger AG. - 1421-9670 .- 0250-8095. ; 50:5, s. 345-356
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Journal article (peer-reviewed)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.
(author)
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Meteor studies in the framework of the JEM-EUSO program
- 2017
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In: Planetary and Space Science. - : Elsevier. - 0032-0633 .- 1873-5088. ; 143, s. 245-255
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Journal article (peer-reviewed)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.
(author)
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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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In: Journal of Instrumentation. - : IOP PUBLISHING LTD. - 1748-0221. ; 13
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Journal article (peer-reviewed)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.
(author)
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FANTOM5 CAGE profiles of human and mouse samples
- 2017
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In: Scientific data. - : Springer Science and Business Media LLC. - 2052-4463. ; 4, s. 170112-
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Journal article (peer-reviewed)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. |
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| 6. |
- Kato, Norihiro, et al.
(author)
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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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In: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 47:11, s. 1282-1293
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Journal article (peer-reviewed)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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| 7. |
- Sassa, Yasmine, et al.
(author)
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The metallic quasi-1D spin-density-wave compound NaV2O4 studied by angle-resolved photoelectron spectroscopy
- 2018
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In: Journal of Electron Spectroscopy and Related Phenomena. - : ELSEVIER SCIENCE BV. - 0368-2048 .- 1873-2526. ; 224, s. 79-83
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Journal article (peer-reviewed)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. |
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| 9. |
- Forslund, Ola Kenji, et al.
(author)
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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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In: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 9:1
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Journal article (peer-reviewed)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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| 10. |
- Nozaki, Hiroshi, et al.
(author)
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Magnetic structure for NaCr2O4 analyzed by neutron diffraction and muon spin-rotation
- 2018
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In: Physica. B, Condensed matter. - : ELSEVIER SCIENCE BV. - 0921-4526 .- 1873-2135. ; 551, s. 137-141
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Journal article (peer-reviewed)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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| 11. |
- Sugiyama, J., et al.
(author)
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Desorption reaction in MgH 2 studied with in situ μ + SR
- 2019
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In: Sustainable Energy & Fuels. - : Royal Society of Chemistry. - 2398-4902. ; 3:4, s. 956-964
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Journal article (peer-reviewed)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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| 12. |
- Eberle, L., et al.
(author)
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Data-driven tiered procedure for enhancing yield in drug product manufacturing
- 2016
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In: Computers and Chemical Engineering. - : Elsevier BV. - 0098-1354. ; 87, s. 82-94
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Journal article (peer-reviewed)abstract
- Enhancing efficiency of pharmaceutical batch production processes is an important challenge in times of increasing public pressure on healthcare costs and decreasing research productivity. This study presents a data-based procedure for systematic yield enhancements in drug product manufacturing, based on four steps. On the first step, production is reviewed to select relevant loss causes, which are assessed on the second step deductively with the goal of assigning measurable parameters. Descriptive Statistical Modelling of loss causes is then performed on the third step, enabling model-based enhancements of processes on the fourth step or, if necessary, a loop-back review of a given loss cause. An industrial case study was performed on production data of 88 batches and demonstrated the applicability of the procedure by prioritizing relevant loss causes, reducing required sample quantities by up to 8% and a cosmetic defect by about 70% by a process change.
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| 13. |
- Hattori, T, et al.
(author)
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Administration of umbilical cord blood cells transiently decreased hypoxic-ischemic brain injury in neonatal rats
- 2015
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In: Developmental neuroscience. - : S. Karger AG. - 1421-9859 .- 0378-5866. ; 37:2, s. 95-104
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Journal article (peer-reviewed)abstract
- This study aimed to investigate whether the administration of mononuclear cells derived from human umbilical cord blood cells (UCBCs) could ameliorate hypoxic-ischemic brain injury in a neonatal rat model. The left carotid arteries of 7-day-old rats were ligated, and the rats were then exposed to 8% oxygen for 60 min. Mononuclear cells derived from UCBCs using the Ficoll-Hypaque technique were injected intraperitoneally 6 h after the insult (1.0 × 10<sup>7</sup> cells). Twenty-four hours after the insult, the number of cells positive for the oxidative stress markers 4-hydroxy-2-nonenal and nitrotyrosine, in the dentate gyrus of the hippocampus in the UCBC-treated group, decreased by 36 and 42%, respectively, compared with those in the control group. In addition, the number of cells positive for the apoptosis markers active caspase-3 and apoptosis-inducing factor decreased by 53 and 58%, respectively. The number of activated microglia (ED1-positive cells) was 51% lower in the UCBC group compared with the control group. In a gait analysis performed 2 weeks after the insult, there were no significant differences among the sham-operated, control and UCBC groups. An active avoidance test using a shuttle box the following week also revealed no significant differences among the groups. Neither the volumes of the hippocampi, corpus callosum and cortices nor the numbers of neurons in the hippocampus were different between the UCBC and control groups. In summary, a single intraperitoneal injection of UCBC-derived mononuclear cells 6 h after an ischemic insult was associated with a transient reduction in numbers of apoptosis and oxidative stress marker-positive cells, but it did not induce long-term morphological or functional protection. Repeated administration or a combination treatment may be required to achieve sustained protection.
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| 14. |
- Kraehling, J. R., et al.
(author)
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Genome-wide RNAi screen reveals ALK1 mediates LDL uptake and transcytosis in endothelial cells
- 2016
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Journal article (peer-reviewed)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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| 15. |
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| 16. |
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| 17. |
- Sugiyama, Jun, et al.
(author)
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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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In: 20TH INTERNATIONAL CONFERENCE ON MAGNETISM, ICM 2015. - : Elsevier. ; , s. 868-875
-
Conference paper (peer-reviewed)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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| 18. |
- Sugiyama, Jun, et al.
(author)
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Magnetic phases in Sr1-xCaxCo2P2 studied by mu+SR
- 2015
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In: 20TH INTERNATIONAL CONFERENCE ON MAGNETISM, ICM 2015. - : Elsevier. ; , s. 426-434
-
Conference paper (peer-reviewed)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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| 19. |
- Sugiyama, Jun, et al.
(author)
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Magnetism of the A-site ordered perovskites CaCu3Cr4O12 and LaCu3Cr4O12
- 2018
-
In: Physical Review B. - : AMER PHYSICAL SOC. - 2469-9950 .- 2469-9969. ; 97:2
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Journal article (peer-reviewed)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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| 20. |
- Sugiyama, Jun, et al.
(author)
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Variation of magnetic ground state of Sr1-xCaxCo2P2 determined with mu(+) SR
- 2015
-
In: Physical Review B. Condensed Matter and Materials Physics. - 1098-0121 .- 1550-235X. ; 91:14
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Journal article (peer-reviewed)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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