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- 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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5. |
- De Zotti, G., et al.
(författare)
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Exploring cosmic origins with CORE : Extragalactic sources in cosmic microwave background maps
- 2018
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Ingår i: Journal of Cosmology and Astroparticle Physics. - : IOP Publishing. - 1475-7516. ; :4
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Tidskriftsartikel (refereegranskat)abstract
- We discuss the potential of a next generation space-borne Cosmic Microwave Background (CMB) experiment for studies of extragalactic sources. Our analysis has particular bearing on the definition of the future space project, CORE, that has been submitted in response to ESA's call for a Medium-size mission opportunity as the successor of the Planck satellite. Even though the effective telescope size will be somewhat smaller than that of Planck, CORE will have a considerably better angular resolution at its highest frequencies, since, in contrast with Planck, it will be diffraction limited at all frequencies. The improved resolution implies a considerable decrease of the source confusion, i.e. substantially fainter detection limits. In particular, CORE will detect thousands of strongly lensed high-z galaxies distributed over the full sky. The extreme brightness of these galaxies will make it possible to study them, via follow-up observations, in extraordinary detail. Also, the CORE resolution matches the typical sizes of high-z galaxy proto-clusters much better than the Planck resolution, resulting in a much higher detection efficiency; these objects will be caught in an evolutionary phase beyond the reach of surveys in other wavebands. Furthermore, CORE will provide unique information on the evolution of the star formation in virialized groups and clusters of galaxies up to the highest possible redshifts. Finally, thanks to its very high sensitivity, CORE will detect the polarized emission of thousands of radio sources and, for the first time, of dusty galaxies, at mm and sub-mm wavelengths, respectively.
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6. |
- Fresard, Laure, et al.
(författare)
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Identification of rare-disease genes using blood transcriptome sequencing and large control cohorts
- 2019
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Ingår i: Nature Medicine. - : NATURE PUBLISHING GROUP. - 1078-8956 .- 1546-170X. ; 25:6, s. 911-919
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Tidskriftsartikel (refereegranskat)abstract
- It is estimated that 350 million individuals worldwide suffer from rare diseases, which are predominantly caused by mutation in a single gene(1). The current molecular diagnostic rate is estimated at 50%, with whole-exome sequencing (WES) among the most successful approaches(2-5). For patients in whom WES is uninformative, RNA sequencing (RNA-seq) has shown diagnostic utility in specific tissues and diseases(6-8). This includes muscle biopsies from patients with undiagnosed rare muscle disorders(6,9), and cultured fibroblasts from patients with mitochondrial disorders(7). However, for many individuals, biopsies are not performed for clinical care, and tissues are difficult to access. We sought to assess the utility of RNA-seq from blood as a diagnostic tool for rare diseases of different pathophysiologies. We generated whole-blood RNA-seq from 94 individuals with undiagnosed rare diseases spanning 16 diverse disease categories. We developed a robust approach to compare data from these individuals with large sets of RNA-seq data for controls (n = 1,594 unrelated controls and n = 49 family members) and demonstrated the impacts of expression, splicing, gene and variant filtering strategies on disease gene identification. Across our cohort, we observed that RNA-seq yields a 7.5% diagnostic rate, and an additional 16.7% with improved candidate gene resolution.
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8. |
- Burigana, C., et al.
(författare)
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Exploring cosmic origins with CORE : Effects of observer peculiar motion
- 2018
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Ingår i: Journal of Cosmology and Astroparticle Physics. - : IOP Publishing. - 1475-7516. ; :4
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Tidskriftsartikel (refereegranskat)abstract
- We discuss the effects on the cosmic microwave background (CMB), cosmic infrared background (CIB), and thermal Sunyaev-Zeldovich effect due to the peculiar motion of an observer with respect to the CMB rest frame, which induces boosting effects. After a brief review of the current observational and theoretical status, we investigate the scientific perspectives opened by future CMB space missions, focussing on the Cosmic Origins Explorer (CORE) proposal. The improvements in sensitivity offered by a mission like CORE, together with its high resolution over a wide frequency range, will provide a more accurate estimate of the CMB dipole. The extension of boosting effects to polarization and cross-correlations will enable a more robust determination of purely velocity-driven effects that are not degenerate with the intrinsic CMB dipole, allowing us to achieve an overall signal-to-noise ratio of 13; this improves on the Planck detection and essentially equals that of an ideal cosmic variance-limited experiment up to a multipole l similar or equal to 2000. Precise inter-frequency calibration will offer the opportunity to constrain or even detect CMB spectral distortions, particularly from the cosmological reionization epoch, because of the frequency dependence of the dipole spectrum, without resorting to precise absolute calibration. The expected improvement with respect to COBE-FIRAS in the recovery of distortion parameters (which could in principle be a factor of several hundred for an ideal experiment with the CORE configuration) ranges from a factor of several up to about 50, depending on the quality of foreground removal and relative calibration. Even in the case of similar or equal to 1% accuracy in both foreground removal and relative calibration at an angular scale of 1 degrees, we find that dipole analyses for a mission like CORE will be able to improve the recovery of the CIB spectrum amplitude by a factor similar or equal to 17 in comparison with current results based on COBE-FIRAS. In addition to the scientific potential of a mission like CORE for these analyses, synergies with other planned and ongoing projects are also discussed.
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10. |
- Di Valentino, E., et al.
(författare)
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Exploring cosmic origins with CORE : Cosmological parameters
- 2018
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Ingår i: Journal of Cosmology and Astroparticle Physics. - : IOP Publishing. - 1475-7516. ; :4
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Tidskriftsartikel (refereegranskat)abstract
- We forecast the main cosmological parameter constraints achievable with the CORE space mission which is dedicated to mapping the polarisation of the Cosmic Microwave Background (CMB). CORE was recently submitted in response to ESA's fifth call for medium-sized mission proposals (M5). Here we report the results from our pre-submission study of the impact of various instrumental options, in particular the telescope size and sensitivity level, and review the great, transformative potential of the mission as proposed. Specifically, we assess the impact on a broad range of fundamental parameters of our Universe as a function of the expected CMB characteristics, with other papers in the series focusing on controlling astrophysical and instrumental residual systematics. In this paper, we assume that only a few central CORE frequency channels are usable for our purpose, all others being devoted to the cleaning of astrophysical contaminants. On the theoretical side, we assume ACDM as our general framework and quantify the improvement provided by CORE over the current constraints from the Planck 2015 release. We also study the joint sensitivity of CORE and of future Baryon Acoustic Oscillation and Large Scale Structure experiments like DESI and Euclid. Specific constraints on the physics of inflation are presented in another paper of the series. In addition to the six parameters of the base ACDM, which describe the matter content of a spatially flat universe with adiabatic and scalar primordial fluctuations from inflation, we derive the precision achievable on parameters like those describing curvature, neutrino physics, extra light relics, primordial helium abundance, dark matter annihilation, recombination physics, variation of fundamental constants, dark energy, modified gravity, reionization and cosmic birefringence. In addition to assessing the improvement on the precision of individual parameters, we also forecast the post-CORE overall reduction of the allowed parameter space with figures of merit for various models increasing by as much as similar to 10(7) as compared to Planck 2015, and 10(5) with respect to Planck 2015 + future BAO measurements.
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11. |
- Finelli, F., et al.
(författare)
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Exploring cosmic origins with CORE : Inflation
- 2018
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Ingår i: Journal of Cosmology and Astroparticle Physics. - : IOP Publishing. - 1475-7516. ; 2018:4
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Tidskriftsartikel (refereegranskat)abstract
- We forecast the scientific capabilities to improve our understanding of cosmic inflation of CORE, a proposed CMB space satellite submitted in response to the ESA fifth call for a medium-size mission opportunity. The CORE satellite will map the CMB anisotropies in temperature and polarization in 19 frequency channels spanning the range 60-600 GHz. CORE will have an aggregate noise sensitivity of 1.7 mu K.arcmin and an angular resolution of 5' at 200 GHz. We explore the impact of telescope size and noise sensitivity on the inflation science return by making forecasts for several instrumental configurations. This study assumes that the lower and higher frequency channels suffice to remove foreground contaminations and complements other related studies of component separation and systematic effects, which will be reported in other papers of the series Exploring Cosmic Origins with CORE. We forecast the capability to determine key inflationary parameters, to lower the detection limit for the tensor-to-scalar ratio down to the 10(-3) level, to chart the landscape of single field slow-roll inflationary models, to constrain the epoch of reheating, thus connecting inflation to the standard radiation-matter dominated Big Bang era, to reconstruct the primordial power spectrum, to constrain the contribution from isocurvature perturbations to the 10(-3) level, to improve constraints on the cosmic string tension to a level below the presumptive GUT scale, and to improve the current measurements of primordial non-Gaussianities down to the f(NL)(local) < 1 level. For all the models explored, CORE alone will improve significantly on the present constraints on the physics of inflation. Its capabilities will be further enhanced by combining with complementary future cosmological observations.
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12. |
- Challinor, A., et al.
(författare)
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Exploring cosmic origins with CORE : Gravitational lensing of the CMB
- 2018
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Ingår i: Journal of Cosmology and Astroparticle Physics. - : IOP Publishing. - 1475-7516. ; :4
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Tidskriftsartikel (refereegranskat)abstract
- Lensing of the cosmic microwave background (CMB) is now a well-developed probe of the clustering of the large-scale mass distribution over a broad range of redshifts. By exploiting the non-Gaussian imprints of lensing in the polarization of the CMB, the CORE mission will allow production of a clean map of the lensing deflections over nearly the full-sky. The number of high-SAN modes in this map will exceed current CMB lensing maps by a factor of 40, and the measurement will be sample-variance limited on all scales where linear theory is valid. Here, we summarise this mission product and discuss the science that will follow from its power spectrum and the cross-correlation with other clustering data. For example, the summed mass of neutrinos will be determined to an accuracy of 17 meV combining CORE lensing and CMB two-point information with contemporaneous measurements of the baryon acoustic oscillation feature in the clustering of galaxies, three times smaller than the minimum total mass allowed by neutrino oscillation measurements. Lensing has applications across many other science goals of CORE, including the search for B-mode polarization from primordial gravitational waves. Here, lens-induced B-modes will dominate over instrument noise, limiting constraints on the power spectrum amplitude of primordial gravitational waves. With lensing reconstructed by CORE, one can delens the observed polarization internally, reducing the lensing B-mode power by 60 %. This can be improved to 70 % by combining lensing and measurements of the cosmic infrared background from CORE, leading to an improvement of a factor of 2.5 in the error on the amplitude of primordial gravitational waves compared to no delensing (in the null hypothesis of no primordial B-modes). Lensing measurements from CORE will allow calibration of the halo masses of the tens of thousands of galaxy clusters that it will find, with constraints dominated by the clean polarization-based estimators. The 19 frequency channels proposed for CORE will allow accurate removal of Galactic emission from CMB maps. We present initial findings that show that residual Galactic foreground contamination will not be a significant source of bias for lensing power spectrum measurements with CORE.
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13. |
- Remazeilles, M., et al.
(författare)
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Exploring cosmic origins with CORE : B-mode component separation
- 2018
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Ingår i: Journal of Cosmology and Astroparticle Physics. - : IOP Publishing. - 1475-7516. ; :4
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Tidskriftsartikel (refereegranskat)abstract
- We demonstrate that, for the baseline design of the CORE satellite mission, the polarized foregrounds can be controlled at the level required to allow the detection of the primordial cosmic microwave background (CMB) B-mode polarization with the desired accuracy at both reionization and recombination scales, for tensor-to-scalar ratio values of r greater than or similar to 5 x 10(-3). We consider detailed sky simulations based on state-of-the-art CMB observations that consist of CMB polarization with tau = 0.055 and tensor-to-scalar values ranging from r = 10(-2) to 10(-3), Galactic synchrotron, and thermal dust polarization with variable spectral indices over the sky, polarized anomalous microwave emission, polarized infrared and radio sources, and gravitational lensing effects. Using both parametric and blind approaches, we perform full component separation and likelihood analysis of the simulations, allowing us to quantify both uncertainties and biases on the reconstructed primordial B-modes. Under the assumption of perfect control of lensing effects, CORE would measure an unbiased estimate of r = (5 +/- 0.4) x 10(-3) after foreground cleaning. In the presence of both gravitational lensing effects and astrophysical foregrounds, the significance of the detection is lowered, with CORE achieving a 4 sigma-measurement of r = 5 x 10(-3) after foreground cleaning and 60% de lensing. For lower tensor-to-scalar ratios (r = 10(-3)) the overall uncertainty on r is dominated by foreground residuals, not by the 40% residual of lensing cosmic variance. Moreover, the residual contribution of unprocessed polarized point-sources can be the dominant foreground contamination to primordial B-modes at this r level, even on relatively large angular scales, l similar to 50. Finally, we report two sources of potential bias for the detection of the primordial B-modes by future CMB experiments: (i) the use of incorrect foreground models, e.g. a modelling error of Delta beta(s) = 0.02 on the synchrotron spectral indices may result in an excess in the recovered reionization peak corresponding to an effective Delta r > 10(-3); (ii) the average of the foreground line-of-sight spectral indices by the combined effects of pixelization and beam convolution, which adds an effective curvature to the foreground spectral energy distribution and may cause spectral degeneracies with the CMB in the frequency range probed by the experiment.
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14. |
- Bernal, Ximena E., et al.
(författare)
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Empowering Latina scientists
- 2019
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 363:6429, s. 825-826
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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15. |
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16. |
- da Silva, R., et al.
(författare)
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Oxygen, sulfur, and iron radial abundance gradients of classical Cepheids across the Galactic thin disk
- 2023
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 678, s. A195-A195
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Tidskriftsartikel (refereegranskat)abstract
- Context. Classical Cepheids (CCs) are solid distance indicators and tracers of young stellar populations. Dating back to the beginning of the 20th century, they have been safely adopted to trace the rotation, kinematics, and chemical enrichment history of the Galactic thin disk.Aims. The main aim of this investigation is to provide iron, oxygen, and sulfur abundances for the largest and most homogeneous sample of Galactic CCs analyzed so far (1118 spectra of 356 objects). The current sample, containing 70 CCs for which spectroscopic metal abundances are provided for the first time, covers a wide range in galactocentric distances, pulsation modes, and pulsation periods.Methods. Optical high-resolution spectra with a high signal-to-noise ratio that were collected with different spectrographs were adopted to provide homogeneous estimates of the atmospheric parameters (effective temperature, surface gravity, and microturbulent velocity) that are required to determine the abundance. Individual distances were based either on trigonometric parallaxes by the Gaia Data Release 3 (Gaia DR3) or on distances based on near-infrared period-luminosity relations.Results. We found that iron and α-element radial gradients based on CCs display a well-defined change in the slope for galactocentric distances larger than ~12 kpc. We also found that logarithmic regressions account for the variation in [X/H] abundances from the inner to the outer disk. Radial gradients for the same elements, but based on open clusters covering a wide range in cluster ages, display similar trends. This means that the flattening in the outer disk is an intrinsic feature of the radial gradients because it is independent of age. Empirical evidence indicates that the S radial gradient is steeper than the Fe radial gradient. The difference in the slope is a factor of two in the linear fit (−0.081 vs. −0.041 dex kpc−1) and changes from −1.62 to −0.91 in the logarithmic distance. Moreover, we found that S (explosive nucleosynthesis) is underabundant on average when compared with O (hydrostatic nucleosynthesis). The difference becomes clearer in the metal-poor regime and for the [O/Fe] and [S/Fe] abundance ratios. We performed a detailed comparison with Galactic chemical evolution models and found that a constant star formation efficiency for galactocentric distances larger than 12 kpc accounts for the flattening observed in both iron and α-elements. To further constrain the impact of the predicted S yields for massive stars on radial gradients, we adopted a toy model and found that the flattening in the outermost regions requires a decrease of a factor of four in the current S predictions.Conclusions. CCs are solid beacons for tracing the recent chemical enrichment of young stellar populations. Sulfur photospheric abundances, when compared with other α-elements, have the key advantage of being a volatile element. Therefore, stellar S abundances can be directly compared with nebular sulfur abundances in external galaxies.
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21. |
- Abazajian, Kevork, et al.
(författare)
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CMB-S4 : Forecasting Constraints on Primordial Gravitational Waves
- 2022
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 926:1
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Tidskriftsartikel (refereegranskat)abstract
- CMB-S4—the next-generation ground-based cosmic microwave background (CMB) experiment—is set to significantly advance the sensitivity of CMB measurements and enhance our understanding of the origin and evolution of the universe. Among the science cases pursued with CMB-S4, the quest for detecting primordial gravitational waves is a central driver of the experimental design. This work details the development of a forecasting framework that includes a power-spectrum-based semianalytic projection tool, targeted explicitly toward optimizing constraints on the tensor-to-scalar ratio, r, in the presence of Galactic foregrounds and gravitational lensing of the CMB. This framework is unique in its direct use of information from the achieved performance of current Stage 2–3 CMB experiments to robustly forecast the science reach of upcoming CMB-polarization endeavors. The methodology allows for rapid iteration over experimental configurations and offers a flexible way to optimize the design of future experiments, given a desired scientific goal. To form a closed-loop process, we couple this semianalytic tool with map-based validation studies, which allow for the injection of additional complexity and verification of our forecasts with several independent analysis methods. We document multiple rounds of forecasts for CMB-S4 using this process and the resulting establishment of the current reference design of the primordial gravitational-wave component of the Stage-4 experiment, optimized to achieve our science goals of detecting primordial gravitational waves for r > 0.003 at greater than 5σ, or in the absence of a detection, of reaching an upper limit of r < 0.001 at 95% CL.
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22. |
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23. |
- Borroto-Escuela, DO, et al.
(författare)
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The coming together of allosteric and phosphorylation mechanisms in the molecular integration of A2A heteroreceptor complexes in the dorsal and ventral striatal-pallidal GABA neurons
- 2021
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Ingår i: Pharmacological reports : PR. - : Springer Science and Business Media LLC. - 2299-5684 .- 1734-1140. ; 73:4, s. 1096-1108
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Tidskriftsartikel (refereegranskat)abstract
- The role of adenosine A2A receptor (A2AR) and striatal-enriched protein tyrosine phosphatase (STEP) interactions in the striatal-pallidal GABA neurons was recently discussed in relation to A2AR overexpression and cocaine-induced increases of brain adenosine levels. As to phosphorylation, combined activation of A2AR and metabotropic glutamate receptor 5 (mGluR5) in the striatal-pallidal GABA neurons appears necessary for phosphorylation of the GluA1 unit of the AMPA receptor to take place. Robert Yasuda (J Neurochem 152: 270–272, 2020) focused on finding a general mechanism by which STEP activation is enhanced by increased A2AR transmission in striatal-pallidal GABA neurons expressing A2AR and dopamine D2 receptor. In his Editorial, he summarized in a clear way the significant effects of A2AR activation on STEP in the dorsal striatal-pallidal GABA neurons which involves a rise of intracellular levels of calcium causing STEP activation through its dephosphorylation. However, the presence of the A2AR in an A2AR-fibroblast growth factor receptor 1 (FGFR1) heteroreceptor complex can be required in the dorsal striatal-pallidal GABA neurons for the STEP activation. Furthermore, Won et al. (Proc Natl Acad Sci USA 116: 8028–8037, 2019) found in mass spectrometry experiments that the STEP splice variant STEP61 can bind to mGluR5 and inactivate it. In addition, A2AR overexpression can lead to increased formation of A2AR-mGluR5 heterocomplexes in ventral striatal-pallidal GABA neurons. It involves enhanced facilitatory allosteric interactions leading to increased Gq-mediated mGluR5 signaling activating STEP. The involvement of both A2AR and STEP in the actions of cocaine on synaptic downregulation was also demonstrated. The enhancement of mGluR5 protomer activity by the A2AR protomer in A2AR-mGluR5 heterocomplexes in the nucleus accumbens shell appears to have a novel significant role in STEP mechanisms by both enhancing the activation of STEP and being a target for STEP61.
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24. |
- Ferraro, Gino B., et al.
(författare)
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Fatty acid synthesis is required for breast cancer brain metastasis
- 2021
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Ingår i: Nature Cancer. - : Springer Science and Business Media LLC. - 2662-1347. ; 2:4, s. 414-428
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Tidskriftsartikel (refereegranskat)abstract
- Brain metastases are refractory to therapies that control systemic disease in patients with human epidermal growth factor receptor 2-positive breast cancer and the brain microenvironment contributes to this therapy resistance. Nutrient availability can vary across tissues, therefore metabolic adaptations required for brain metastatic breast cancer growth may introduce liabilities that can be exploited for therapy. Here we assessed how metabolism differs between breast tumors in brain versus extracranial sites and found that fatty acid synthesis is elevated in breast tumors growing in the brain. We determine that this phenotype is an adaptation to decreased lipid availability in the brain relative to other tissues, resulting in site-specific dependency on fatty acid synthesis for breast tumors growing at this site. Genetic or pharmacological inhibition of fatty acid synthase reduces human epidermal growth factor receptor 2-positive breast tumor growth in the brain, demonstrating that differences in nutrient availability across metastatic sites can result in targetable metabolic dependencies.
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26. |
- Riedel, M., et al.
(författare)
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Improving e-Science with Interoperability of the e-Infrastructures EGEE and DEISA
- 2008
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Ingår i: MIPRO 2008 - 31st International Convention Proceedings. - 9789532330366 ; , s. 225-231
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Konferensbidrag (refereegranskat)abstract
- In the last couple of years, many e-Science infrastructures have begun to offer production services to e- Scientists with an increasing number of applications that require access to different kinds of computational resources. Within Europe two rather different multi-national e-Science infrastructures evolved over time namely Distributed European Infrastructure for Supercomputing Applications (DEISA) and Enabling Grids for E-SciencE (EGEE). DEISA provides access to massively parallel systems such as supercomputers that are well suited for scientific applications that require many interactions between their typically high numbers of CPUs. EGEE on the other hand provides access to a world-wide Grid of university clusters and PC pools that are well suited for farming applications that require less or even no interactions between the distributed CPUs. While DEISA uses the HPC-driven Grid technology UNICORE, EGEE is based on the gLite Grid middleware optimized for farming jobs. Both have less adoption of open standards and therefore both systems are technically non-interoperable, which means that no e-Scientist can easily leverage the DEISA and EGEE infrastructure with one suitable client environment for scientific applications. This paper argues that future interoperability of such large e-Science infrastructures is required to improve e-Science in general and to increase the real scientific impact of world-wide Grids in particular. We discuss the interoperability achieved by the OMII-Europe project that fundamentally improved the interoperability between UNICORE and gLite by using open standards. We also outline one specific scientific scenario of the WISDOM initiative that actually benefits from the recently established interoperability.
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27. |
- Ade, Peter, et al.
(författare)
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The Simons Observatory : science goals and forecasts
- 2019
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Ingår i: Journal of Cosmology and Astroparticle Physics. - : IOP Publishing. - 1475-7516. ; :2
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Tidskriftsartikel (refereegranskat)abstract
- The Simons Observatory (SO) is a new cosmic microwave background experiment being built on Cerro Toco in Chile, due to begin observations in the early 2020s. We describe the scientific goals of the experiment, motivate the design, and forecast its performance. SO will measure the temperature and polarization anisotropy of the cosmic microwave background in six frequency bands centered at: 27, 39, 93, 145, 225 and 280 GHz. The initial con figuration of SO will have three small-aperture 0.5-m telescopes and one large-aperture 6-m telescope, with a total of 60,000 cryogenic bolometers. Our key science goals are to characterize the primordial perturbations, measure the number of relativistic species and the mass of neutrinos, test for deviations from a cosmological constant, improve our understanding of galaxy evolution, and constrain the duration of reionization. The small aperture telescopes will target the largest angular scales observable from Chile, mapping approximate to 10% of the sky to a white noise level of 2 mu K-arcmin in combined 93 and 145 GHz bands, to measure the primordial tensor-to-scalar ratio, r, at a target level of sigma(r) = 0.003. The large aperture telescope will map approximate to 40% of the sky at arcminute angular resolution to an expected white noise level of 6 mu K-arcmin in combined 93 and 145 GHz bands, overlapping with the majority of the Large Synoptic Survey Telescope sky region and partially with the Dark Energy Spectroscopic Instrument. With up to an order of magnitude lower polarization noise than maps from the Planck satellite, the high-resolution sky maps will constrain cosmological parameters derived from the damping tail, gravitational lensing of the microwave background, the primordial bispectrum, and the thermal and kinematic Sunyaev-Zel'dovich effects, and will aid in delensing the large-angle polarization signal to measure the tensor-to-scalar ratio. The survey will also provide a legacy catalog of 16,000 galaxy clusters and more than 20,000 extragalactic sources.
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28. |
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29. |
- Borroto-Escuela, DO, et al.
(författare)
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The Balance of MU-Opioid, Dopamine D2 and Adenosine A2A Heteroreceptor Complexes in the Ventral Striatal-Pallidal GABA Antireward Neurons May Have a Significant Role in Morphine and Cocaine Use Disorders
- 2021
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Ingår i: Frontiers in pharmacology. - : Frontiers Media SA. - 1663-9812. ; 12, s. 627032-
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Tidskriftsartikel (refereegranskat)abstract
- The widespread distribution of heteroreceptor complexes with allosteric receptor-receptor interactions in the CNS represents a novel integrative molecular mechanism in the plasma membrane of neurons and glial cells. It was proposed that they form the molecular basis for learning and short-and long-term memories. This is also true for drug memories formed during the development of substance use disorders like morphine and cocaine use disorders. In cocaine use disorder it was found that irreversible A2AR-D2R complexes with an allosteric brake on D2R recognition and signaling are formed in increased densities in the ventral enkephalin positive striatal-pallidal GABA antireward neurons. In this perspective article we discuss and propose how an increase in opioid heteroreceptor complexes, containing MOR-DOR, MOR-MOR and MOR-D2R, and their balance with each other and A2AR-D2R complexes in the striatal-pallidal enkephalin positive GABA antireward neurons, may represent markers for development of morphine use disorders. We suggest that increased formation of MOR-DOR complexes takes place in the striatal-pallidal enkephalin positive GABA antireward neurons after chronic morphine treatment in part through recruitment of MOR from the MOR-D2R complexes due to the possibility that MOR upon morphine treatment can develop a higher affinity for DOR. As a result, increased numbers of D2R monomers/homomers in these neurons become free to interact with the A2A receptors found in high densities within such neurons. Increased numbers of A2AR-D2R heteroreceptor complexes are formed and contribute to enhanced firing of these antireward neurons due to loss of inhibitory D2R protomer signaling which finally leads to the development of morphine use disorder. Development of cocaine use disorder may instead be reduced through enkephalin induced activation of the MOR-DOR complex inhibiting the activity of the enkephalin positive GABA antireward neurons. Altogether, we propose that these altered complexes could be pharmacological targets to modulate the reward and the development of substance use disorders.
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30. |
- Borroto-Escuela, DO, et al.
(författare)
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Understanding the Functional Plasticity in Neural Networks of the Basal Ganglia in Cocaine Use Disorder: A Role for Allosteric Receptor-Receptor Interactions in A2A-D2 Heteroreceptor Complexes
- 2016
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Ingår i: Neural plasticity. - : Hindawi Limited. - 1687-5443 .- 2090-5904. ; 2016, s. 4827268-
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Tidskriftsartikel (refereegranskat)abstract
- Our hypothesis is that allosteric receptor-receptor interactions in homo- and heteroreceptor complexes may form the molecular basis of learning and memory. This principle is illustrated by showing how cocaine abuse can alter the adenosine A2AR-dopamine D2R heterocomplexes and their receptor-receptor interactions and hereby induce neural plasticity in the basal ganglia. Studies with A2AR ligands using cocaine self-administration procedures indicate that antagonistic allosteric A2AR-D2R heterocomplexes of the ventral striatopallidal GABA antireward pathway play a significant role in reducing cocaine induced reward, motivation, and cocaine seeking. Anticocaine actions of A2AR agonists can also be produced at A2AR homocomplexes in these antireward neurons, actions in which are independent of D2R signaling. At the A2AR-D2R heterocomplex, they are dependent on the strength of the antagonistic allosteric A2AR-D2R interaction and the number of A2AR-D2R and A2AR-D2R-sigma1R heterocomplexes present in the ventral striatopallidal GABA neurons. It involves a differential cocaine-induced increase in sigma1Rs in the ventral versus the dorsal striatum. In contrast, the allosteric brake on the D2R protomer signaling in the A2AR-D2R heterocomplex of the dorsal striatopallidal GABA neurons is lost upon cocaine self-administration. This is potentially due to differences in composition and allosteric plasticity of these complexes versus those in the ventral striatopallidal neurons.
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31. |
- Chapman, I. T., et al.
(författare)
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Three-dimensional distortions of the tokamak plasma boundary: boundary displacements in the presence of resonant magnetic perturbations
- 2014
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Ingår i: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 54:8, s. Article no. 083006-
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Tidskriftsartikel (refereegranskat)abstract
- The three-dimensional plasma boundary displacements induced by applied non-axisymmetric magnetic perturbations have been measured in ASDEX Upgrade, DIII-D, JET, MAST and NSTX. The displacements arising from applied resonant magnetic perturbations (RMPs) are measured up to +/- 5% of the minor radius in present-day machines. Good agreement can be found between different experimental measurements and a range of models-be it vacuum field line tracing, ideal three-dimensional MHD equilibrium modelling, or nonlinear plasma amplification. The agreement of the various experimental measurements with the different predictions from these models is presented, and the regions of applicability of each discussed. The measured displacement of the outboard boundary from various machines is found to correlate approximately linearly with the applied resonant field predicted by vacuum modelling (though it should be emphasized that one should not infer that vacuum modelling accurately predicts the displacement inside the plasma). The RMP-induced displacements foreseen in ITER are expected to lie within the range of those predicted by the different models, meaning less than +/- 1.75% (+/- 3.5 cm) of the minor radius in the H-mode baseline and less than +/- 2.5% (+/- 5 cm) in a 9MA plasma. Whilst a displacement of 7 cm peak-to-peak in the baseline scenario is marginally acceptable from both a plasma control and heat loading perspective, it is important that ITER adopts a plasma control system which can account for a three-dimensional boundary corrugation to avoid an n = 0 correction which would otherwise locally exacerbate the displacement caused by the applied fields.
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39. |
- Brunelli, M., et al.
(författare)
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Experimental Determination of Irreversible Entropy Production in out-of-Equilibrium Mesoscopic Quantum Systems
- 2018
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Ingår i: Physical Review Letters. - 1079-7114 .- 0031-9007. ; 121:16
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Tidskriftsartikel (refereegranskat)abstract
- By making use of a recently proposed framework for the inference of thermodynamic irreversibility in bosonic quantum systems, we experimentally measure and characterize the entropy production rates in the nonequilibrium steady state of two different physical systems a micromechanical resonator and a Bose-Einstein condensate each coupled to a high finesse cavity and hence also subject to optical loss. Key features of our setups, such as the cooling of the mechanical resonator and signatures of a structural quantum phase transition in the condensate, are reflected in the entropy production rates. Our work demonstrates the possibility to explore irreversibility in driven mesoscopic quantum systems and paves the way to a systematic experimental assessment of entropy production beyond the microscopic limit.
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41. |
- De Angelis, M., et al.
(författare)
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Evaluation of the internal field in lithium niobate ferroelectric domains by an interferometric method
- 2004
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Ingår i: Applied physics letters. - : AIP Publishing. - 0003-6951 .- 1077-3118. ; 85:4, s. 2785-
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Tidskriftsartikel (refereegranskat)abstract
- We report on the evaluation of internal electric field of a ferroelectric engineered-domain in a LiNbO3 wafer crystal by detecting optical path length variation with a noninvasive interferometric inspection method. The lithium niobate wafer has been patterned and subjected to electric field poling to obtain two antiparallel ferroelectric domains separated by a single domain wall. The crystal has been mounted into one arm of a Mach-Zehnder-type interferometer to study the phase map and evaluate the effects of domain reversion by a digital holographic technique. Evaluation of the internal field and consequent variation of the electro-optical properties of the different domains is analyzed.
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- Ferraro, P., et al.
(författare)
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Surface topography of microstructures in lithium niobate by digital holographic microscopy
- 2004
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Ingår i: Measument science and technology15. - : IOP Publishing. - 0957-0233 .- 1361-6501. ; 15:5, s. 961-
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Tidskriftsartikel (refereegranskat)abstract
- We report here on the application of digital holographic microscopy as a metrological tool for the inspection and the micro-topography reconstruction of different microstructures fabricated in bulk lithium niobate by differential etching of reversed ferroelectric domain patterned crystals. These structures have a range of applications in optical ridge waveguides, alignment structures, V-grooves, micro-tips and micro-cantilever beams and precise control of the surface quality and topography is required. The technique allows us to obtain digitally a high-fidelity surface topography description of the specimen with only one image acquisition allowing us to have relatively simple and compact set-ups able to give quantitative information on object morphology. The advantages of this technique compared to traditional microscopy are discussed.
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45. |
- Hossain, M. Akhter, et al.
(författare)
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The A-chain of the human relaxin family peptides has distinct roles in the binding and activation of the different relaxin family peptide receptors
- 2008
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Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 283:25, s. 17287-17297
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Tidskriftsartikel (refereegranskat)abstract
- The relaxin peptides are a family of hormones that share a structural fold characterized by two chains, A and B, that are cross-braced by three disulfide bonds. Relaxins signal through two different classes of G-protein-coupled receptors (GPCRs), leucine-rich repeat-containing GPCRs LGR7 and LGR8 together with GPCR135 and GPCR142, now referred to as the relaxin family peptide (RXFP) receptors 1-4, respectively. Although key binding residues have been identified in the B-chain of the relaxin peptides, the role of the A-chain in their activity is currently unknown. A recent study showed that INSL3 can be truncated at the N terminus of its A-chain by up to 9 residues without affecting the binding affinity to its receptor RXFP2 while becoming a high affinity antagonist. This suggests that the N terminus of the INSL3 A-chain contains residues essential for RXFP2 activation. In this study, we have synthesized A-chain truncated human relaxin-2 and -3 (H2 and H3) relaxin peptides, characterized their structure by both CD and NMR spectroscopy, and tested their binding and cAMP activities on RXFP1, RXFP2, and RXFP3. In stark contrast to INSL3, A-chain-truncated H2 relaxin peptides lost RXFP1 and RXFP2 binding affinity and concurrently cAMP-stimulatory activity. H3 relaxin A-chain-truncated peptides displayed similar properties on RXFP1, highlighting a similar binding mechanism for H2 and H3 relaxin. In contrast, A-chain-truncated H3 relaxin peptides showed identical activity on RXFP3, highlighting that the B-chain is the sole determinant of the H3 relaxin-RXFP3 interaction. Our results provide new insights into the action of relaxins and demonstrate that the role of the A-chain for relaxin activity is both peptide- and receptor-dependent.
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- Mangini, F., et al.
(författare)
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Self-imaging dynamics in nonlinear GRIN multimode optical fibers
- 2020
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Ingår i: Optics InfoBase Conference Papers. - : Optica Publishing Group. - 9781943580804
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Konferensbidrag (refereegranskat)abstract
- We study nonlinear self-imaging dynamics in graded-index multimode optical fibers. Side-scattering of light that accompanies the propagation of intense femtosecond pulses permits us to directly measure the self-imaging period.
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50. |
- Marzolla, M., et al.
(författare)
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Open standards-based interoperability of job submission and management interfaces across the grid middleware platforms gLite and UNICORE
- 2007
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Ingår i: Proceedings - e-Science 2007, 3rd IEEE International Conference on e-Science and Grid Computing. - : IEEE Computer Society. - 0769530648 - 9780769530642 ; , s. 592-599
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Konferensbidrag (refereegranskat)abstract
- In a distributed Grid environment with ambitious service demands the job submission and management interfaces provide functionality of major importance. Emerging e-Science and Grid infrastructures such as EGEE and DEISA rely on highly available services that are capable of managing scientific jobs. It is the adoption of emerging open standard interfaces which allows the distribution of Grid resources in such a way that their actual service implementation or Grid technologies are not isolated from each other, especially when these resources are deployed in different e-Science infrastructures that consist of different types of computational resources. This paper motivates the interoperability of these infrastructures and discusses solutions. We describe the adoption of various open standards that recently emerged from the Open Grid Forum (OGF) in the field of job submission and management by well-known Grid technologies, respectively gLite and UNICORE. This has a fundamental impact on the interoperability between these technologies and thus within the next generation e-Science infrastructures that rely on these technologies.
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