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Sökning: WFRF:(Halpern A.)

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1.
  • Ruilope, LM, et al. (författare)
  • Design and Baseline Characteristics of the Finerenone in Reducing Cardiovascular Mortality and Morbidity in Diabetic Kidney Disease Trial
  • 2019
  • Ingår i: American journal of nephrology. - : S. Karger AG. - 1421-9670 .- 0250-8095. ; 50:5, s. 345-356
  • 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.
  • Fenstermacher, M.E., et al. (författare)
  • DIII-D research advancing the physics basis for optimizing the tokamak approach to fusion energy
  • 2022
  • Ingår i: Nuclear Fusion. - : IOP Publishing. - 0029-5515 .- 1741-4326. ; 62:4
  • 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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3.
  • Abdo, A. A., et al. (författare)
  • FERMI LARGE AREA TELESCOPE DETECTION OF PULSED gamma-RAYS FROM THE VELA-LIKE PULSARS PSR J1048-5832 AND PSR J2229+6114
  • 2009
  • Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 706:2, s. 1331-1340
  • Tidskriftsartikel (refereegranskat)abstract
    • We report the detection of gamma-ray pulsations (>= 0.1GeV) from PSR J2229+ 6114 and PSR J1048-5832, the latter having been detected as a low-significance pulsar by EGRET. Data in the gamma-ray band were acquired by the Large Area Telescope (LAT) aboard the Fermi Gamma-ray Space Telescope, while the radio rotational ephemerides used to fold the gamma-ray light curves were obtained using the Green Bank Telescope, the Lovell telescope at Jodrell Bank, and the Parkes Telescope. The two young radio pulsars, located within the error circles of the previously unidentified EGRET sources 3EG J1048-5840 and 3EG J2227+6122, present spin-down characteristics similar to the Vela pulsar. PSR J1048-5832 shows two sharp peaks at phases 0.15 +/- 0.01 and 0.57 +/- 0.01 relative to the radio pulse confirming the EGRET light curve, while PSR J2229+ 6114 presents a very broad peak at phase 0.49 +/- 0.01. The gamma-ray spectra above 0.1 GeV of both pulsars are fit with power laws having exponential cutoffs near 3 GeV, leading to integral photon fluxes of (2.19 +/- 0.22 +/- 0.32) x 10(-7) cm(-2) s(-1) for PSR J1048-5832 and (3.77 +/- 0.22 +/- 0.44) x 10(-7) cm(-2) s(-1) for PSR J2229+6114. The first uncertainty is statistical and the second is systematic. PSR J1048-5832 is one of the two LAT sources whichwere entangled together as 3EG J1048-5840. These detections add to the growing number of young gamma-ray pulsars that make up the dominant population of GeV gamma-ray sources in the Galactic plane.
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4.
  • Abdo, A. A., et al. (författare)
  • Fermi Large Area Telescope Detection of Pulsed γ-rays from the Vela-like Pulsars PSR J1048–5832 and PSR J2229+6114
  • 2009
  • Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 706:2, s. 1331-1340
  • Tidskriftsartikel (refereegranskat)abstract
    • We report the detection of γ-ray pulsations (>=0.1 GeV) from PSR J2229+6114 and PSR J1048–5832, the latter having been detected as a low-significance pulsar by EGRET. Data in the γ-ray band were acquired by the Large Area Telescope (LAT) aboard the Fermi Gamma-ray Space Telescope, while the radio rotational ephemerides used to fold the γ-ray light curves were obtained using the Green Bank Telescope, the Lovell telescope at Jodrell Bank, and the Parkes Telescope. The two young radio pulsars, located within the error circles of the previously unidentified EGRET sources 3EG J1048–5840 and 3EG J2227+6122, present spin-down characteristics similar to the Vela pulsar. PSR J1048–5832 shows two sharp peaks at phases 0.15 ± 0.01 and 0.57 ± 0.01 relative to the radio pulse confirming the EGRET light curve, while PSR J2229+6114 presents a very broad peak at phase 0.49 ± 0.01. The γ-ray spectra above 0.1 GeV of both pulsars are fit with power laws having exponential cutoffs near 3 GeV, leading to integral photon fluxes of (2.19 ± 0.22 ± 0.32) × 10–7 cm–2 s–1 for PSR J1048–5832 and (3.77 ± 0.22 ± 0.44) × 10–7 cm–2 s–1 for PSR J2229+6114. The first uncertainty is statistical and the second is systematic. PSR J1048–5832 is one of the two LAT sources which were entangled together as 3EG J1048–5840. These detections add to the growing number of young γ-ray pulsars that make up the dominant population of GeV γ-ray sources in the Galactic plane.
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5.
  • Archambault, S., et al. (författare)
  • Discovery of a New TeV Gamma-Ray Source : VER J0521+211
  • 2013
  • Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 776:2
  • Tidskriftsartikel (refereegranskat)abstract
    • We report the detection of a new TeV gamma-ray source, VER J0521+211, based on observations made with the VERITAS imaging atmospheric Cherenkov Telescope Array. These observations were motivated by the discovery of a cluster of >30 GeV photons in the first year of Fermi Large Area Telescope observations. VER J0521+211 is relatively bright at TeV energies, with a mean photon flux of (1.93 ± 0.13stat ± 0.78sys) × 10–11 cm–2 s–1 above 0.2 TeV during the period of the VERITAS observations. The source is strongly variable on a daily timescale across all wavebands, from optical to TeV, with a peak flux corresponding to ~0.3 times the steady Crab Nebula flux at TeV energies. Follow-up observations in the optical and X-ray bands classify the newly discovered TeV source as a BL Lac-type blazar with uncertain redshift, although recent measurements suggest z = 0.108. VER J0521+211 exhibits all the defining properties of blazars in radio, optical, X-ray, and gamma-ray wavelengths.
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6.
  • Bergman, A. S., et al. (författare)
  • 280 GHz Focal Plane Unit Design and Characterization for the SPIDER-2 Suborbital Polarimeter
  • 2018
  • Ingår i: Journal of Low Temperature Physics. - : Springer Science and Business Media LLC. - 0022-2291 .- 1573-7357. ; 193:5-6, s. 1075-1084
  • Tidskriftsartikel (refereegranskat)abstract
    • We describe the construction and characterization of the 280 GHz bolometric focal plane units (FPUs) to be deployed on the second flight of the balloon-borne SPIDER instrument. These FPUs are vital to SPIDER's primary science goal of detecting or placing an upper limit on the amplitude of the primordial gravitational wave signature in the cosmic microwave background (CMB) by constraining the B-mode contamination in the CMB from Galactic dust emission. Each 280 GHz focal plane contains a 16 x 16 grid of corrugated silicon feedhorns coupled to an array of aluminum-manganese transition-edge sensor (TES) bolometers fabricated on 150 mm diameter substrates. In total, the three 280 GHz FPUs contain 1530 polarization-sensitive bolometers (765 spatial pixels) optimized for the low loading environment in flight and read out by time-division SQUID multiplexing. In this paper, we describe the mechanical, thermal, and magnetic shielding architecture of the focal planes and present cryogenic measurements which characterize yield and the uniformity of several bolometer parameters. The assembled FPUs have high yields, with one array as high as 95% including defects from wiring and readout. We demonstrate high uniformity in device parameters, finding the median saturation power for each TES array to be similar to 3 pW at 300 mK with a less than 6% variation across each array at 1 sigma. These focal planes will be deployed alongside the 95 and 150 GHz telescopes in the SPIDER-2 instrument, slated to fly from McMurdo Station in Antarctica in December 2018.
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7.
  • Clark, Andrew G., et al. (författare)
  • Evolution of genes and genomes on the Drosophila phylogeny
  • 2007
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 450:7167, s. 203-218
  • Tidskriftsartikel (refereegranskat)abstract
    • Comparative analysis of multiple genomes in a phylogenetic framework dramatically improves the precision and sensitivity of evolutionary inference, producing more robust results than single-genome analyses can provide. The genomes of 12 Drosophila species, ten of which are presented here for the first time (sechellia, simulans, yakuba, erecta, ananassae, persimilis, willistoni, mojavensis, virilis and grimshawi), illustrate how rates and patterns of sequence divergence across taxa can illuminate evolutionary processes on a genomic scale. These genome sequences augment the formidable genetic tools that have made Drosophila melanogaster a pre-eminent model for animal genetics, and will further catalyse fundamental research on mechanisms of development, cell biology, genetics, disease, neurobiology, behaviour, physiology and evolution. Despite remarkable similarities among these Drosophila species, we identified many putatively non-neutral changes in protein-coding genes, non-coding RNA genes, and cis-regulatory regions. These may prove to underlie differences in the ecology and behaviour of these diverse species.
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8.
  • Leung, J. S.-Y., et al. (författare)
  • A Simulation-based Method for Correcting Mode Coupling in CMB Angular Power Spectra
  • 2022
  • Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 928:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Modern cosmic microwave background (CMB) analysis pipelines regularly employ complex time-domain filters, beam models, masking, and other techniques during the production of sky maps and their corresponding angular power spectra. However, these processes can generate couplings between multipoles from the same spectrum and from different spectra, in addition to the typical power attenuation. Within the context of pseudo-C-l based, MASTER-style analyses, the net effect of the time-domain filtering is commonly approximated by a multiplicative transfer function, F-l , that can fail to capture mode mixing and is dependent on the spectrum of the signal. To address these shortcomings, we have developed a simulation-based spectral correction approach that constructs a two-dimensional transfer matrix, J(ll'), which contains information about mode mixing in addition to mode attenuation. We demonstrate the application of this approach on data from the first flight of the Spider balloon-borne CMB experiment.
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9.
  • Ade, P. A. R., et al. (författare)
  • A Constraint on Primordial B-modes from the First Flight of the Spider Balloon-borne Telescope
  • 2022
  • Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 927:2
  • Tidskriftsartikel (refereegranskat)abstract
    • We present the first linear polarization measurements from the 2015 long-duration balloon flight of SPIDER, which is an experiment that is designed to map the polarization of the cosmic microwave background (CMB) on degree angular scales. The results from these measurements include maps and angular power spectra from observations of 4.8% of the sky at 95 and 150 GHz, along with the results of internal consistency tests on these data. While the polarized CMB anisotropy from primordial density perturbations is the dominant signal in this region of sky, Galactic dust emission is also detected with high significance. Galactic synchrotron emission is found to be negligible in the SPIDER bands. We employ two independent foreground-removal techniques to explore the sensitivity of the cosmological result to the assumptions made by each. The primary method uses a dust template derived from Planck data to subtract the Galactic dust signal. A second approach, which constitutes a joint analysis of SPIDER and Planck data in the harmonic domain, assumes a modified-blackbody model for the spectral energy distribution of the dust with no constraint on its spatial morphology. Using a likelihood that jointly samples the template amplitude and r parameter space, we derive 95% upper limits on the primordial tensor-to-scalar ratio from Feldman-Cousins and Bayesian constructions, finding r < 0.11 and r < 0.19, respectively. Roughly half the uncertainty in r derives from noise associated with the template subtraction. New data at 280 GHz from SPIDER´s second flight will complement the Planck polarization maps, providing powerful measurements of the polarized Galactic dust emission.
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10.
  • Filippini, J. P., et al. (författare)
  • In-Flight Gain Monitoring of SPIDER's Transition-Edge Sensor Arrays
  • 2022
  • Ingår i: Journal of Low Temperature Physics. - : Springer Science and Business Media LLC. - 0022-2291 .- 1573-7357. ; 209:3-4, s. 649-657
  • Tidskriftsartikel (refereegranskat)abstract
    • Experiments deploying large arrays of transition-edge sensors (TESs) often require a robust method to monitor gain variations with minimal loss of observing time. We propose a sensitive and non-intrusive method for monitoring variations in TES responsivity using small square waves applied to the TES bias. We construct an estimator for a TES's small-signal power response from its electrical response that is exact in the limit of strong electrothermal feedback. We discuss the application and validation of this method using flight data from SPIDER, a balloon-borne telescope that observes the polarization of the cosmic microwave background with more than 2000 TESs. This method may prove useful for future balloon- and space-based instruments, where observing time and ground control bandwidth are limited.
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