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1.
  • Adrian-Martinez, S., et al. (författare)
  • A first search for coincident gravitational waves and high energy neutrinos using LIGO, Virgo and ANTARES data from 2007
  • 2013
  • Ingår i: Journal of Cosmology and Astroparticle Physics. - : IOP Publishing. - 1475-7516. ; :6
  • Tidskriftsartikel (refereegranskat)abstract
    • We present the results of the first search for gravitational wave bursts associated with high energy neutrinos. Together, these messengers could reveal new, hidden sources that are not observed by conventional photon astronomy, particularly at high energy. Our search uses neutrinos detected by the underwater neutrino telescope ANTARES in its 5 line configuration during the period January - September 2007, which coincided with the fifth and first science runs of LIGO and Virgo, respectively. The LIGO-Virgo data were analysed for candidate gravitational-wave signals coincident in time and direction with the neutrino events. No significant coincident events were observed. We place limits on the density of joint high energy neutrino - gravitational wave emission events in the local universe, and compare them with densities of merger and core-collapse events.
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2.
  • Aasi, J., et al. (författare)
  • Parameter estimation for compact binary coalescence signals with the first generation gravitational-wave detector network
  • 2013
  • Ingår i: Physical Review D (Particles, Fields, Gravitation and Cosmology). - 1550-2368. ; 88:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Compact binary systems with neutron stars or black holes are one of the most promising sources for ground-based gravitational-wave detectors. Gravitational radiation encodes rich information about source physics; thus parameter estimation and model selection are crucial analysis steps for any detection candidate events. Detailed models of the anticipated waveforms enable inference on several parameters, such as component masses, spins, sky location and distance, that are essential for new astrophysical studies of these sources. However, accurate measurements of these parameters and discrimination of models describing the underlying physics are complicated by artifacts in the data, uncertainties in the waveform models and in the calibration of the detectors. Here we report such measurements on a selection of simulated signals added either in hardware or software to the data collected by the two LIGO instruments and the Virgo detector during their most recent joint science run, including a "blind injection'' where the signal was not initially revealed to the collaboration. We exemplify the ability to extract information about the source physics on signals that cover the neutron-star and black-hole binary parameter space over the component mass range 1M(circle dot)-25M(circle dot) and the full range of spin parameters. The cases reported in this study provide a snapshot of the status of parameter estimation in preparation for the operation of advanced detectors.
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3.
  • Aasi, J., et al. (författare)
  • Einstein@Home all-sky search for periodic gravitational waves in LIGO S5 data
  • 2013
  • Ingår i: Physical Review D (Particles, Fields, Gravitation and Cosmology). - 1550-2368. ; 87:4
  • Tidskriftsartikel (refereegranskat)abstract
    • This paper presents results of an all-sky search for periodic gravitational waves in the frequency range [50, 1190] Hz and with frequency derivative range of similar to[-20, 1.1] x 10(-10) Hz s(-1) for the fifth LIGO science run (S5). The search uses a noncoherent Hough-transform method to combine the information from coherent searches on time scales of about one day. Because these searches are very computationally intensive, they have been carried out with the Einstein@Home volunteer distributed computing project. Postprocessing identifies eight candidate signals; deeper follow-up studies rule them out. Hence, since no gravitational wave signals have been found, we report upper limits on the intrinsic gravitational wave strain amplitude h(0). For example, in the 0.5 Hz-wide band at 152.5 Hz, we can exclude the presence of signals with h(0) greater than 7.6 x 10(-25) at a 90% confidence level. This search is about a factor 3 more sensitive than the previous Einstein@Home search of early S5 LIGO data.
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4.
  • Aasi, J., et al. (författare)
  • Search for gravitational waves from binary black hole inspiral, merger, and ringdown in LIGO-Virgo data from 2009-2010
  • 2013
  • Ingår i: Physical Review D (Particles, Fields, Gravitation and Cosmology). - 1550-2368. ; 87:2
  • Tidskriftsartikel (refereegranskat)abstract
    • We report a search for gravitational waves from the inspiral, merger and ringdown of binary black holes (BBH) with total mass between 25 and 100 solar masses, in data taken at the LIGO and Virgo observatories between July 7, 2009 and October 20, 2010. The maximum sensitive distance of the detectors over this period for a (20, 20)M-circle dot coalescence was 300 Mpc. No gravitational wave signals were found. We thus report upper limits on the astrophysical coalescence rates of BBH as a function of the component masses for nonspinning components, and also evaluate the dependence of the search sensitivity on component spins aligned with the orbital angular momentum. We find an upper limit at 90% confidence on the coalescence rate of BBH with nonspinning components of mass between 19 and 28M(circle dot) of 3:3 x 10(-7) mergers Mpc(-3) yr(-1).
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5.
  • Aasi, J., et al. (författare)
  • The characterization of Virgo data and its impact on gravitational-wave searches
  • 2012
  • Ingår i: Classical and Quantum Gravity. - : IOP Publishing. - 1361-6382 .- 0264-9381. ; 29:15
  • Tidskriftsartikel (refereegranskat)abstract
    • Between 2007 and 2010 Virgo collected data in coincidence with the LIGO and GEO gravitational-wave (GW) detectors. These data have been searched for GWs emitted by cataclysmic phenomena in the universe, by non-axisymmetric rotating neutron stars or from a stochastic background in the frequency band of the detectors. The sensitivity of GW searches is limited by noise produced by the detector or its environment. It is therefore crucial to characterize the various noise sources in a GW detector. This paper reviews the Virgo detector noise sources, noise propagation, and conversion mechanisms which were identified in the three first Virgo observing runs. In many cases, these investigations allowed us to mitigate noise sources in the detector, or to selectively flag noise events and discard them from the data. We present examples from the joint LIGO-GEO-Virgo GW searches to show how well noise transients and narrow spectral lines have been identified and excluded from the Virgo data. We also discuss how detector characterization can improve the astrophysical reach of GW searches.
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6.
  • Evans, P. A., et al. (författare)
  • Swift Follow-up Observations of Candidate Gravitational-wave Transient Events
  • 2012
  • Ingår i: The Astrophysical Journal Supplement Series. - : American Astronomical Society. - 0067-0049 .- 1538-4365. ; 203:2
  • Tidskriftsartikel (refereegranskat)abstract
    • We present the first multi-wavelength follow-up observations of two candidate gravitational-wave (GW) transient events recorded by LIGO and Virgo in their 2009-2010 science run. The events were selected with low latency by the network of GW detectors (within less than 10 minutes) and their candidate sky locations were observed by the Swift observatory (within 12 hr). Image transient detection was used to analyze the collected electromagnetic data, which were found to be consistent with background. Off-line analysis of the GW data alone has also established that the selected GW events show no evidence of an astrophysical origin; one of them is consistent with background and the other one was a test, part of a "blind injection challenge." With this work we demonstrate the feasibility of rapid follow-ups of GW transients and establish the sensitivity improvement joint electromagnetic and GW observations could bring. This is a first step toward an electromagnetic follow-up program in the regime of routine detections with the advanced GW instruments expected within this decade. In that regime, multi-wavelength observations will play a significant role in completing the astrophysical identification of GW sources. We present the methods and results from this first combined analysis and discuss its implications in terms of sensitivity for the present and future instruments.
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7.
  • Abadie, J., et al. (författare)
  • All-sky search for gravitational-wave bursts in the second joint LIGO-Virgo run
  • 2012
  • Ingår i: Physical Review D (Particles, Fields, Gravitation and Cosmology). - 1550-2368. ; 85:12
  • Tidskriftsartikel (refereegranskat)abstract
    • We present results from a search for gravitational-wave bursts in the data collected by the LIGO and Virgo detectors between July 7, 2009 and October 20, 2010: data are analyzed when at least two of the three LIGO-Virgo detectors are in coincident operation, with a total observation time of 207 days. The analysis searches for transients of duration less than or similar to 1 s over the frequency band 64-5000 Hz, without other assumptions on the signal waveform, polarization, direction or occurrence time. All identified events are consistent with the expected accidental background. We set frequentist upper limits on the rate of gravitational-wave bursts by combining this search with the previous LIGO-Virgo search on the data collected between November 2005 and October 2007. The upper limit on the rate of strong gravitational-wave bursts at the Earth is 1.3 events per year at 90% confidence. We also present upper limits on source rate density per year and Mpc(3) for sample populations of standard-candle sources. As in the previous joint run, typical sensitivities of the search in terms of the root-sum-squared strain amplitude for these waveforms lie in the range similar to 5 x 10(-22) Hz(-1/2) to similar to 1 x 10(-20) Hz(-1/2). The combination of the two joint runs entails the most sensitive all-sky search for generic gravitational-wave bursts and synthesizes the results achieved by the initial generation of interferometric detectors.
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8.
  • Abadie, J., et al. (författare)
  • First low-latency LIGO plus Virgo search for binary inspirals and their electromagnetic counterparts
  • 2012
  • Ingår i: Astronomy & Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 541
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims. The detection and measurement of gravitational-waves from coalescing neutron-star binary systems is an important science goal for ground-based gravitational-wave detectors. In addition to emitting gravitational-waves at frequencies that span the most sensitive bands of the LIGO and Virgo detectors, these sources are also amongst the most likely to produce an electromagnetic counterpart to the gravitational-wave emission. A joint detection of the gravitational-wave and electromagnetic signals would provide a powerful new probe for astronomy. Methods. During the period between September 19 and October 20, 2010, the first low-latency search for gravitational-waves from binary inspirals in LIGO and Virgo data was conducted. The resulting triggers were sent to electromagnetic observatories for followup. We describe the generation and processing of the low-latency gravitational-wave triggers. The results of the electromagnetic image analysis will be described elsewhere. Results. Over the course of the science run, three gravitational-wave triggers passed all of the low-latency selection cuts. Of these, one was followed up by several of our observational partners. Analysis of the gravitational-wave data leads to an estimated false alarm rate of once every 6.4 days, falling far short of the requirement for a detection based solely on gravitational-wave data.
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9.
  • Abadie, J., et al. (författare)
  • Search for Gravitational Waves Associated with Gamma-Ray Bursts during LIGO Science Run 6 and Virgo Science Runs 2 and 3
  • 2012
  • Ingår i: Astrophysical Journal. - 0004-637X. ; 760:1
  • Tidskriftsartikel (refereegranskat)abstract
    • We present the results of a search for gravitational waves associated with 154 gamma-ray bursts (GRBs) that were detected by satellite-based gamma-ray experiments in 2009-2010, during the sixth LIGO science run and the second and third Virgo science runs. We perform two distinct searches: a modeled search for coalescences of either two neutron stars or a neutron star and black hole, and a search for generic, unmodeled gravitational-wave bursts. We find no evidence for gravitational-wave counterparts, either with any individual GRB in this sample or with the population as a whole. For all GRBs we place lower bounds on the distance to the progenitor, under the optimistic assumption of a gravitational-wave emission energy of 10(-2) M-circle dot c(2) at 150 Hz, with a median limit of 17 Mpc. For short-hard GRBs we place exclusion distances on binary neutron star and neutron-star-black-hole progenitors, using astrophysically motivated priors on the source parameters, with median values of 16 Mpc and 28 Mpc, respectively. These distance limits, while significantly larger than for a search that is not aided by GRB satellite observations, are not large enough to expect a coincidence with a GRB. However, projecting these exclusions to the sensitivities of Advanced LIGO and Virgo, which should begin operation in 2015, we find that the detection of gravitational waves associated with GRBs will become quite possible.
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10.
  • Abadie, J., et al. (författare)
  • Search for gravitational waves from intermediate mass binary black holes
  • 2012
  • Ingår i: Physical Review D (Particles, Fields, Gravitation and Cosmology). - 1550-2368. ; 85:10
  • Tidskriftsartikel (refereegranskat)abstract
    • We present the results of a weakly modeled burst search for gravitational waves from mergers of nonspinning intermediate mass black holes in the total mass range 100-450 M-circle dot and with the component mass ratios between 1: and 4:1. The search was conducted on data collected by the LIGO and Virgo detectors between November of 2005 and October of 2007. No plausible signals were observed by the search which constrains the astrophysical rates of the intermediate mass black holes mergers as a function of the component masses. In the most efficiently detected bin centered on 88 + 88 M-circle dot, for nonspinning sources, the rate density upper limit is 0.13 per Mpc(3) per Myr at the 90% confidence level.
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11.
  • Abadie, J., et al. (författare)
  • Upper limits on a stochastic gravitational-wave background using LIGO and Virgo interferometers at 600-1000 Hz
  • 2012
  • Ingår i: Physical Review D (Particles, Fields, Gravitation and Cosmology). - 1550-2368. ; 85:12
  • Tidskriftsartikel (refereegranskat)abstract
    • A stochastic background of gravitational waves is expected to arise from a superposition of many incoherent sources of gravitational waves, of either cosmological or astrophysical origin. This background is a target for the current generation of ground-based detectors. In this article we present the first joint search for a stochastic background using data from the LIGO and Virgo interferometers. In a frequency band of 600-1000 Hz, we obtained a 95% upper limit on the amplitude of Omega(GW)(f) = Omega(3)(f/900 Hz)(3), of Omega(3) < 0.32, assuming a value of the Hubble parameter of h(100) = 0.71. These new limits are a factor of seven better than the previous best in this frequency band.
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12.
  • Abadie, J., et al. (författare)
  • All-sky search for periodic gravitational waves in the full S5 LIGO data
  • 2012
  • Ingår i: Physical Review D (Particles, Fields, Gravitation and Cosmology). - 1550-2368. ; 85:2
  • Tidskriftsartikel (refereegranskat)abstract
    • We report on an all-sky search for periodic gravitational waves in the frequency band 50-800 Hz and with the frequency time derivative in the range of 0 through -6 x 10(-9) Hz/s. Such a signal could be produced by a nearby spinning and slightly nonaxisymmetric isolated neutron star in our Galaxy. After recent improvements in the search program that yielded a 10x increase in computational efficiency, we have searched in two years of data collected during LIGO's fifth science run and have obtained the most sensitive all-sky upper limits on gravitational-wave strain to date. Near 150 Hz our upper limit on worst-case linearly polarized strain amplitude h(0) is 1 x 10(-24), while at the high end of our frequency range we achieve a worst-case upper limit of 3.8 x 10(-24) for all polarizations and sky locations. These results constitute a factor of 2 improvement upon previously published data. A new detection pipeline utilizing a loosely coherent algorithm was able to follow up weaker outliers, increasing the volume of space where signals can be detected by a factor of 10, but has not revealed any gravitational-wave signals. The pipeline has been tested for robustness with respect to deviations from the model of an isolated neutron star, such as caused by a low-mass or long-period binary companion.
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13.
  • Abadie, J., et al. (författare)
  • Implementation and testing of the first prompt search for gravitational wave transients with electromagnetic counterparts
  • 2012
  • Ingår i: Astronomy & Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 539
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims. A transient astrophysical event observed in both gravitational wave (GW) and electromagnetic (EM) channels would yield rich scientific rewards. A first program initiating EM follow-ups to possible transient GW events has been developed and exercised by the LIGO and Virgo community in association with several partners. In this paper, we describe and evaluate the methods used to promptly identify and localize GW event candidates and to request images of targeted sky locations. Methods. During two observing periods (Dec. 17, 2009 to Jan. 8, 2010 and Sep. 2 to Oct. 20, 2010), a low-latency analysis pipeline was used to identify GW event candidates and to reconstruct maps of possible sky locations. A catalog of nearby galaxies and Milky Way globular clusters was used to select the most promising sky positions to be imaged, and this directional information was delivered to EM observatories with time lags of about thirty minutes. A Monte Carlo simulation has been used to evaluate the low-latency GW pipeline's ability to reconstruct source positions correctly. Results. For signals near the detection threshold, our low-latency algorithms often localized simulated GW burst signals to tens of square degrees, while neutron star/neutron star inspirals and neutron star/black hole inspirals were localized to a few hundred square degrees. Localization precision improves for moderately stronger signals. The correct sky location of signals well above threshold and originating from nearby galaxies may be observed with similar to 50% or better probability with a few pointings of wide-field telescopes.
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14.
  • Abadie, J., et al. (författare)
  • Search for gravitational waves from low mass compact binary coalescence in LIGO's sixth science run and Virgo's science runs 2 and 3
  • 2012
  • Ingår i: Physical Review D (Particles, Fields, Gravitation and Cosmology). - 1550-2368. ; 85:8
  • Tidskriftsartikel (refereegranskat)abstract
    • We report on a search for gravitational waves from coalescing compact binaries using LIGO and Virgo observations between July 7, 2009, and October 20, 2010. We searched for signals from binaries with total mass between 2 and 25M(circle dot); this includes binary neutron stars, binary black holes, and binaries consisting of a black hole and neutron star. The detectors were sensitive to systems up to 40 Mpc distant for binary neutron stars, and further for higher mass systems. No gravitational-wave signals were detected. We report upper limits on the rate of compact binary coalescence as a function of total mass, including the results from previous LIGO and Virgo observations. The cumulative 90% confidence rate upper limits of the binary coalescence of binary neutron star, neutron star-black hole, and binary black hole systems are 1.3 x 10(-4), 3.1 x 10(-5), and 6.4 x 10(-6) Mpc(-3) yr(-1), respectively. These upper limits are up to a factor 1.4 lower than previously derived limits. We also report on results from a blind injection challenge.
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  • 2017
  • Ingår i: Physical Review D. - 2470-0010 .- 2470-0029. ; 96:2
  • Tidskriftsartikel (refereegranskat)
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  • Tinetti, Giovanna, et al. (författare)
  • The EChO science case
  • 2015
  • Ingår i: Experimental astronomy. - : Springer Science and Business Media LLC. - 0922-6435 .- 1572-9508. ; 40:2-3, s. 329-391
  • Tidskriftsartikel (refereegranskat)abstract
    • The discovery of almost two thousand exoplanets has revealed an unexpectedly diverse planet population. We see gas giants in few-day orbits, whole multi-planet systems within the orbit of Mercury, and new populations of planets with masses between that of the Earth and Neptune-all unknown in the Solar System. Observations to date have shown that our Solar System is certainly not representative of the general population of planets in our Milky Way. The key science questions that urgently need addressing are therefore: What are exoplanets made of? Why are planets as they are? How do planetary systems work and what causes the exceptional diversity observed as compared to the Solar System? The EChO (Exoplanet Characterisation Observatory) space mission was conceived to take up the challenge to explain this diversity in terms of formation, evolution, internal structure and planet and atmospheric composition. This requires in-depth spectroscopic knowledge of the atmospheres of a large and well-defined planet sample for which precise physical, chemical and dynamical information can be obtained. In order to fulfil this ambitious scientific program, EChO was designed as a dedicated survey mission for transit and eclipse spectroscopy capable of observing a large, diverse and well-defined planet sample within its 4-year mission lifetime. The transit and eclipse spectroscopy method, whereby the signal from the star and planet are differentiated using knowledge of the planetary ephemerides, allows us to measure atmospheric signals from the planet at levels of at least 10(-4) relative to the star. This can only be achieved in conjunction with a carefully designed stable payload and satellite platform. It is also necessary to provide broad instantaneous wavelength coverage to detect as many molecular species as possible, to probe the thermal structure of the planetary atmospheres and to correct for the contaminating effects of the stellar photosphere. This requires wavelength coverage of at least 0.55 to 11 mu m with a goal of covering from 0.4 to 16 mu m. Only modest spectral resolving power is needed, with R similar to 300 for wavelengths less than 5 mu m and R similar to 30 for wavelengths greater than this. The transit spectroscopy technique means that no spatial resolution is required. A telescope collecting area of about 1 m(2) is sufficiently large to achieve the necessary spectro-photometric precision: for the Phase A study a 1.13 m(2) telescope, diffraction limited at 3 mu m has been adopted. Placing the satellite at L2 provides a cold and stable thermal environment as well as a large field of regard to allow efficient time-critical observation of targets randomly distributed over the sky. EChO has been conceived to achieve a single goal: exoplanet spectroscopy. The spectral coverage and signal-to-noise to be achieved by EChO, thanks to its high stability and dedicated design, would be a game changer by allowing atmospheric composition to be measured with unparalleled exactness: at least a factor 10 more precise and a factor 10 to 1000 more accurate than current observations. This would enable the detection of molecular abundances three orders of magnitude lower than currently possible and a fourfold increase from the handful of molecules detected to date. Combining these data with estimates of planetary bulk compositions from accurate measurements of their radii and masses would allow degeneracies associated with planetary interior modelling to be broken, giving unique insight into the interior structure and elemental abundances of these alien worlds. EChO would allow scientists to study exoplanets both as a population and as individuals. The mission can target super-Earths, Neptune-like, and Jupiter-like planets, in the very hot to temperate zones (planet temperatures of 300-3000 K) of F to M-type host stars. The EChO core science would be delivered by a three-tier survey. The EChO Chemical Census: This is a broad survey of a few-hundred exoplanets, which allows us to explore the spectroscopic and chemical diversity of the exoplanet population as a whole. The EChO Origin: This is a deep survey of a subsample of tens of exoplanets for which significantly higher signal to noise and spectral resolution spectra can be obtained to explain the origin of the exoplanet diversity (such as formation mechanisms, chemical processes, atmospheric escape). The EChO Rosetta Stones: This is an ultra-high accuracy survey targeting a subsample of select exoplanets. These will be the bright "benchmark" cases for which a large number of measurements would be taken to explore temporal variations, and to obtain two and three dimensional spatial information on the atmospheric conditions through eclipse-mapping techniques. If EChO were launched today, the exoplanets currently observed are sufficient to provide a large and diverse sample. The Chemical Census survey would consist of > 160 exoplanets with a range of planetary sizes, temperatures, orbital parameters and stellar host properties. Additionally, over the next 10 years, several new ground- and space-based transit photometric surveys and missions will come on-line (e.g. NGTS, CHEOPS, TESS, PLATO), which will specifically focus on finding bright, nearby systems. The current rapid rate of discovery would allow the target list to be further optimised in the years prior to EChO's launch and enable the atmospheric characterisation of hundreds of planets.
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  • Zouganelis, I., et al. (författare)
  • The Solar Orbiter Science Activity Plan : Translating solar and heliospheric physics questions into action
  • 2020
  • Ingår i: Astronomy and Astrophysics. - : EDP SCIENCES S A. - 0004-6361 .- 1432-0746. ; 642
  • Tidskriftsartikel (refereegranskat)abstract
    • Solar Orbiter is the first space mission observing the solar plasma both in situ and remotely, from a close distance, in and out of the ecliptic. The ultimate goal is to understand how the Sun produces and controls the heliosphere, filling the Solar System and driving the planetary environments. With six remote-sensing and four in-situ instrument suites, the coordination and planning of the operations are essential to address the following four top-level science questions: (1) What drives the solar wind and where does the coronal magnetic field originate?; (2) How do solar transients drive heliospheric variability?; (3) How do solar eruptions produce energetic particle radiation that fills the heliosphere?; (4) How does the solar dynamo work and drive connections between the Sun and the heliosphere? Maximising the mission's science return requires considering the characteristics of each orbit, including the relative position of the spacecraft to Earth (affecting downlink rates), trajectory events (such as gravitational assist manoeuvres), and the phase of the solar activity cycle. Furthermore, since each orbit's science telemetry will be downloaded over the course of the following orbit, science operations must be planned at mission level, rather than at the level of individual orbits. It is important to explore the way in which those science questions are translated into an actual plan of observations that fits into the mission, thus ensuring that no opportunities are missed. First, the overarching goals are broken down into specific, answerable questions along with the required observations and the so-called Science Activity Plan (SAP) is developed to achieve this. The SAP groups objectives that require similar observations into Solar Orbiter Observing Plans, resulting in a strategic, top-level view of the optimal opportunities for science observations during the mission lifetime. This allows for all four mission goals to be addressed. In this paper, we introduce Solar Orbiter's SAP through a series of examples and the strategy being followed.
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  • Abe, O, et al. (författare)
  • Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials
  • 2005
  • Ingår i: The Lancet. - 1474-547X. ; 365:9472, s. 1687-1717
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Quinquennial overviews (1985-2000) of the randomised trials in early breast cancer have assessed the 5-year and 10-year effects of various systemic adjuvant therapies on breast cancer recurrence and survival. Here, we report the 10-year and 15-year effects. Methods Collaborative meta-analyses were undertaken of 194 unconfounded randomised trials of adjuvant chemotherapy or hormonal therapy that began by 1995. Many trials involved CMF (cyclophosphamide, methotrexate, fluorouracil), anthracycline-based combinations such as FAC (fluorouracil, doxombicin, cyclophosphamide) or FEC (fluorouracil, epirubicin, cyclophosphamide), tamoxifen, or ovarian suppression: none involved taxanes, trastuzumab, raloxifene, or modem aromatase inhibitors. Findings Allocation to about 6 months of anthracycline-based polychemotherapy (eg, with FAC or FEC) reduces the annual breast cancer death rate by about 38% (SE 5) for women younger than 50 years of age when diagnosed and by about 20% (SE 4) for those of age 50-69 years when diagnosed, largely irrespective of the use of tamoxifen and of oestrogen receptor (ER) status, nodal status, or other tumour characteristics. Such regimens are significantly (2p=0 . 0001 for recurrence, 2p<0 . 00001 for breast cancer mortality) more effective than CMF chemotherapy. Few women of age 70 years or older entered these chemotherapy trials. For ER-positive disease only, allocation to about 5 years of adjuvant tamoxifen reduces the annual breast cancer death rate by 31% (SE 3), largely irrespective of the use of chemotherapy and of age (<50, 50-69, &GE; 70 years), progesterone receptor status, or other tumour characteristics. 5 years is significantly (2p<0 . 00001 for recurrence, 2p=0 . 01 for breast cancer mortality) more effective than just 1-2 years of tamoxifen. For ER-positive tumours, the annual breast cancer mortality rates are similar during years 0-4 and 5-14, as are the proportional reductions in them by 5 years of tamoxifen, so the cumulative reduction in mortality is more than twice as big at 15 years as at 5 years after diagnosis. These results combine six meta-analyses: anthracycline-based versus no chemotherapy (8000 women); CMF-based versus no chemotherapy (14 000); anthracycline-based versus CMF-based chemotherapy (14 000); about 5 years of tamoxifen versus none (15 000); about 1-2 years of tamoxifen versus none (33 000); and about 5 years versus 1-2 years of tamoxifen (18 000). Finally, allocation to ovarian ablation or suppression (8000 women) also significantly reduces breast cancer mortality, but appears to do so only in the absence of other systemic treatments. For middle-aged women with ER-positive disease (the commonest type of breast cancer), the breast cancer mortality rate throughout the next 15 years would be approximately halved by 6 months of anthracycline-based chemotherapy (with a combination such as FAC or FEC) followed by 5 years of adjuvant tamoxifen. For, if mortality reductions of 38% (age <50 years) and 20% (age 50-69 years) from such chemotherapy were followed by a further reduction of 31% from tamoxifen in the risks that remain, the final mortality reductions would be 57% and 45%, respectively (and, the trial results could well have been somewhat stronger if there had been full compliance with the allocated treatments). Overall survival would be comparably improved, since these treatments have relatively small effects on mortality from the aggregate of all other causes. Interpretation Some of the widely practicable adjuvant drug treatments that were being tested in the 1980s, which substantially reduced 5-year recurrence rates (but had somewhat less effect on 5-year mortality rates), also substantially reduce 15-year mortality rates. Further improvements in long-term survival could well be available from newer drugs, or better use of older drugs.
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  • Domingo-Pardo, C., et al. (författare)
  • Advances and new ideas for neutron-capture astrophysics experiments at CERN n_TOF
  • 2023
  • Ingår i: European Physical Journal A. - : Springer. - 1434-6001 .- 1434-601X. ; 59:1
  • Tidskriftsartikel (refereegranskat)abstract
    • This article presents a few selected developments and future ideas related to the measurement of (n,γ) data of astrophysical interest at CERN n_TOF. The MC-aided analysis methodology for the use of low-efficiency radiation detectors in time-of-flight neutron-capture measurements is discussed, with particular emphasis on the systematic accuracy. Several recent instrumental advances are also presented, such as the development of total-energy detectors with γ-ray imaging capability for background suppression, and the development of an array of small-volume organic scintillators aimed at exploiting the high instantaneous neutron-flux of EAR2. Finally, astrophysics prospects related to the intermediate i neutron-capture process of nucleosynthesis are discussed in the context of the new NEAR activation area.
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  • Alcayne, V., et al. (författare)
  • A Segmented Total Energy Detector (sTED) optimized for (n,ϒ) cross-section measurements at n_TOF EAR2
  • 2024
  • Ingår i: Radiation Physics and Chemistry. - : Elsevier. - 0969-806X .- 1879-0895. ; 217
  • Tidskriftsartikel (refereegranskat)abstract
    • The neutron time-of-flight facility n_TOF at CERN is a spallation source dedicated to measurements of neutroninduced reaction cross-sections of interest in nuclear technologies, astrophysics, and other applications. Since 2014, Experimental ARea 2 (EAR2) is operational and delivers a neutron fluence of similar to 4 center dot 10(7) neutrons per nominal proton pulse, which is similar to 50 times higher than the one of Experimental ARea 1 (EAR1) of similar to 8 center dot 10(5) neutrons per pulse. The high neutron flux at EAR2 results in high counting rates in the detectors that challenged the previously existing capture detection systems. For this reason, a Segmented Total Energy Detector (sTED) has been developed to overcome the limitations in the detector's response, by reducing the active volume per module and by using a photo-multiplier (PMT) optimized for high counting rates. This paper presents the main characteristics of the sTED, including energy and time resolution, response to gamma-rays, and provides as well details of the use of the Pulse Height Weighting Technique (PHWT) with this detector. The sTED has been validated to perform neutron-capture cross-section measurements in EAR2 in the neutron energy range from thermal up to at least 400 keV. The detector has already been successfully used in several measurements at n_TOF EAR2.
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30.
  • Balibrea-Correa, J., et al. (författare)
  • First measurement of the 94Nb(n,γ) cross section at the CERN n_TOF facility
  • 2023
  • Ingår i: EPJ Web of Conferences. - : EDP Sciences. - 2100-014X. ; 279
  • Tidskriftsartikel (refereegranskat)abstract
    • One of the crucial ingredients for the improvement of stellar models is the accurate knowledge of neutron capture cross-sections for the different isotopes involved in the s-,r- and i- processes. These measurements can shed light on existing discrepancies between observed and predicted isotopic abundances and help to constrain the physical conditions where these reactions take place along different stages of stellar evolution.In the particular case of the radioactive 94Nb, the 94Nb(n,γ) cross-section could play a role in the determination of the s-process production of 94Mo in AGB stars, which presently cannot be reproduced by state-of-the-art stellar models. There are no previous 94Nb(n,γ) experimental data for the resolved and unresolved resonance regions mainly due to the difficulties in producing highquality samples and also due to limitations in conventional detection systems commonly used in time-of-flight experiments.Motivated by this situation, a first measurement of the 94Nb(n,γ) reaction was carried out at CERN n_TOF, thereby exploiting the high luminosity of the EAR2 area in combination with a new detection system of small-volume C6D6-detectors and a high quality 94Nb-sample. The latter was based on hyper-pure 93Nb material activated at the high-flux reactor of ILL-Grenoble. An innovative ring-configuration detection system in close geometry around the capture sample allowed us to significantly enhance the signal-to-background ratio. This set-up was supplemented with two conventional C6D6-detectors and a highresolution LaCl3(Ce)-detector, which will be employed for addressing reliably systematic effects and uncertainties.At the current status of the data analysis, 18 resonance in 94Nb+n have been observed for the first time in the neutron energy range from thermal up to 10 keV.
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31.
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32.
  • Domingo-Pardo, C., et al. (författare)
  • Compton imaging for enhanced sensitivity (n,gamma) cross section TOF experiments : Status and prospects
  • 2023
  • Ingår i: 15TH INTERNATIONAL CONFERENCE ON NUCLEAR DATA FOR SCIENCE AND TECHNOLOGY, ND2022. - : EDP Sciences.
  • Konferensbidrag (refereegranskat)abstract
    • Radiative neutron-capture cross sections are of pivotal importance in many fields such as nucle-osynthesis studies or innovative reactor technologies. A large number of isotopes have been measured with high accuracy, but there are still a large number of relevant isotopes whose cross sections could not be experimentally determined yet, at least with sufficient accuracy and completeness, owing to limitations in detection techniques, sample production methods or in the facilities themselves. In the context of the HYMNS (High-sensitivitY Measurements of key stellar Nucleo-Synthesis reactions) project over the last six years we have developed a novel detection technique aimed at background suppression in radiative neutron-capture time-of-flight measurements. This new technique utilizes a complex detection set-up based on position-sensitive radiation-detectors deployed in a Compton-camera array configuration. The latter enables to implement gamma-ray imaging techniques, which help to disentangle true capture events arising from the sample under study and contaminant background events from the surroundings. A summary on the main developments is given in this contribution together with an update on recent experiments at CERN n_TOF and an outlook on future steps.
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33.
  • Domingo-Pardo, C., et al. (författare)
  • The neutron time-of-flight facility n_TOF at CERN Recent facility upgrades and detector developments
  • 2023
  • Ingår i: Journal of Physics, Conference Series. - : Institute of Physics (IOP). - 1742-6588 .- 1742-6596. ; 2586
  • Tidskriftsartikel (refereegranskat)abstract
    • Based on an idea by Carlo Rubbia, the n_TOF facility at CERN has been operating for over 20 years. It is a neutron spallation source, driven by the 20 GeV/c proton beam from the CERN PS accelerator. Neutrons in a very wide energy range (from GeV, down to sub-eV kinetic energy) are generated by a massive Lead spallation target feeding two experimental areas. EAR1, horizonal with respect to the proton beam direction is set at 185 meters from the spallation target. EAR2, on the vertical line from the spallation source, is placed at 20 m. Neutron energies for experiments are selected by the time-of-flight technique (hence the name n_TOF), while the long flight paths ensure a very good energy resolution. Over one hundred experiments have been performed by the n_TOF Collaboration at CERN, with applications ranging from nuclear astrophysics (synthesis of the heavy elements in stars, big bang nucleosynthesis, nuclear cosmo-chronology), to advanced nuclear technologies (nuclear data for applications, nuclear safety), as well as for basic nuclear science (reaction mechanisms, structure and decay of highly excited compound states). During the planned shutdown of the CERN accelerator complex between 2019 and 2021, the facility went through a substantial upgrade with a new target-moderator assembly, refurbishing of the neutron beam lines and experimental areas. An additional measuring and irradiation station (the NEAR Station) has been envisaged and its capabilities for performing material test studies and new physics opportunities are presently explored. An overview of the facility and of the activities performed at CERN is presented in this contribution, with a particular emphasis on the most relevant experiments for nuclear astrophysics.
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34.
  • Dupont, E., et al. (författare)
  • Overview of the dissemination of n_TOF experimental data and resonance parameters
  • 2023
  • Ingår i: 15TH INTERNATIONAL CONFERENCE ON NUCLEAR DATA FOR SCIENCE AND TECHNOLOGY, ND2022. - : EDP Sciences.
  • Konferensbidrag (refereegranskat)abstract
    • The n_TOF neutron time-of-flight facility at CERN is used for nuclear data measurements. The n_TOF Collaboration works closely with the Nuclear Reaction Data Centres (NRDC) network to disseminate the experimental data through the international EXFOR library. In addition, the Collaboration helps integrate the results in the evaluated library projects. The present contribution describes the dissemination status of n_TOF results, their impact on evaluated libraries and ongoing efforts to provide n_TOF resonance parameters in ENDF-6 format for further use by evaluation projects.
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35.
  • Lerendegui-Marco, J., et al. (författare)
  • New detection systems for an enhanced sensitivity in key stellar (n,γ) measurements
  • 2023
  • Ingår i: EPJ Web of Conferences. - : EDP Sciences. - 2100-014X. ; 279
  • Tidskriftsartikel (refereegranskat)abstract
    • Neutron capture cross-section measurements are fundamental in the study of astrophysical phenomena, such as the slow neutron capture (s-) process of nucleosynthesis operating in red-giant and massive stars. However, neutron capture measurements via the time-of-flight (TOF) technique on key s-process nuclei are often challenging. Difficulties arise from the limited mass (∼mg) available and the high sample-related background in the case of the unstable s-process branching points. Measurements on neutron magic nuclei, that act as s-process bottlenecks, are affected by low (n,γ) cross sections and a dominant neutron scattering background. Overcoming these experimental challenges requires the combination of facilities with high instantaneous flux, such as n_TOFEAR2, with detection systems with an enhanced detection sensitivity and high counting rate capabilities. This contribution reviews some of the latest detector developments in detection systems for (n,γ) measurements at n_TOF, such as i-TED, an innovative detection system which exploits the Compton imaging technique to reduce the dominant neutron scattering background and s-TED, a highly segmented total energy detector intended for high flux facilities. The discussion will be illustrated with results of the first measurement of key the s-process branching-point reaction 79Se(n,γ).
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36.
  • Lerendegui-Marco, J., et al. (författare)
  • New perspectives for neutron capture measurements in the upgraded CERN-n_TOF Facility
  • 2023
  • Ingår i: 15th International Conference on Nuclear Data for Science and Technology, ND2022. - : EDP Sciences.
  • Konferensbidrag (refereegranskat)abstract
    • The n_TOF facility has just undergone in 2021 a major upgrade with the installation of its third generation spallation target that has been designed to optimize the performance of the two n_TOF time-of-flight lines. This contribution describes the key features and limitations for capture measurements in the two beam lines prior to the target upgrade and presents first results of (n,gamma) measurements carried out as part of the commissioning of the upgraded facility. In particular, the energy resolution, a key factor for both increasing the signal-to background ratio and obtaining accurate resonance parameters, has been clearly improved for the 20 m long vertical beam-line with the new target design while keeping the remarkably high resolution of the long beamline n_TOF-EAR1. The improvements in the n_TOF neutron beam-lines need to be accompanied by improvements in the instrumentation. A review is given on recent detector R&D projects aimed at tackling the existing challenges and further improving the capabilities of this facility.
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37.
  • Maksimovic, M., et al. (författare)
  • First observations and performance of the RPW instrument on board the Solar Orbiter mission
  • 2021
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 656
  • Tidskriftsartikel (refereegranskat)abstract
    • The Radio and Plasma Waves (RPW) instrument on the ESA Solar Orbiter mission is designed to measure in situ magnetic and electric fields and waves from the continuum up to several hundred kHz. The RPW also observes solar and heliospheric radio emissions up to 16 MHz. It was switched on and its antennae were successfully deployed two days after the launch of Solar Orbiter on February 10, 2020. Since then, the instrument has acquired enough data to make it possible to assess its performance and the electromagnetic disturbances it experiences. In this article, we assess its scientific performance and present the first RPW observations. In particular, we focus on a statistical analysis of the first observations of interplanetary dust by the instrument's Thermal Noise Receiver. We also review the electro-magnetic disturbances that RPW suffers, especially those which potential users of the instrument data should be aware of before starting their research work.
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38.
  • Maksimovic, M., et al. (författare)
  • The Solar Orbiter Radio and Plasma Waves (RPW) instrument
  • 2020
  • Ingår i: Astronomy and Astrophysics. - : EDP SCIENCES S A. - 0004-6361 .- 1432-0746. ; 642
  • Tidskriftsartikel (refereegranskat)abstract
    • The Radio and Plasma Waves (RPW) instrument on the ESA Solar Orbiter mission is described in this paper. This instrument is designed to measure in-situ magnetic and electric fields and waves from the continuous to a few hundreds of kHz. RPW will also observe solar radio emissions up to 16 MHz. The RPW instrument is of primary importance to the Solar Orbiter mission and science requirements since it is essential to answer three of the four mission overarching science objectives. In addition RPW will exchange on-board data with the other in-situ instruments in order to process algorithms for interplanetary shocks and type III langmuir waves detections.
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39.
  • Massimi, C., et al. (författare)
  • Neutron-induced cross section measurements
  • 2023
  • Ingår i: EPJ Web of Conferences. - : EDP Sciences. - 2100-014X. ; 279
  • Tidskriftsartikel (refereegranskat)abstract
    • Neutron-induced cross sections represent the main nuclear input to models of stellar and Big-Bang nucleosynthesis. While (n,γ) reactions are relevant for the formation of elements heavier than iron, (n,p) and (n,α) reactions can play an important role in specific cases. The time-of-flight method is routinely used at n_TOF to experimentally determine the cross section data. In addition, recent upgrades of the facility will allow the use of activation techniques as well, possibly opening the way to a systematic study of neutron interaction with radioactive isotopes. In the last 20 years n_TOF has provided a large amount of experimental data for Nuclear Astrophysics. Our plan is to carry on challenging measurements and produce nuclear data in the next decades as well.
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40.
  • Mastromarco, M., et al. (författare)
  • Measurement of the Gd-160(n, gamma) cross section at n_TOF and its medical implications
  • 2023
  • Ingår i: 15TH INTERNATIONAL CONFERENCE ON NUCLEAR DATA FOR SCIENCE AND TECHNOLOGY, ND2022. - : EDP Sciences.
  • Konferensbidrag (refereegranskat)abstract
    • Neutron-capture reactions on gadolinium isotopes play an important role in several fields of physics, in particular in nuclear Astrophysics for the understanding of the nucleosynthesis of heavy elements (beyond iron) in stars via the s- and r-processes [1] and in nuclear technology. Another important application of gadolinium is linked to the production of terbium, that offers a set of clinically interesting isotopes for theranostics, characterized by complementary physical decay characteristics. In particular, the low -energy beta(-) emitter terbium-161 is very similar to lutetium-177 in terms of half-life (6.89 d), beta(-) - energy and chemical properties. Being a significant emitter of conversion/Auger electrons, greater therapeutic effect can therefore be expected in comparison to Lu-177 [2, 3]. For this reason, in the last decade, the study of the neutron capture reaction Gd-160(n,,gamma)(161) Gd and the subsequent beta(-) - decay in terbium-161 is getting particular attention. As the nuclear data on the Gd-160 neutron capture reaction are quite scarce and inconsistent, a new measurement of the capture cross section of Gd-160 at the CERN neutron Time -Of-Flight facilty was performed in order to provide high resolution, high -accuracy data on this important reaction, in the energy range from thermal to hundreds of keV. In this contribution, the preliminary results of the n_TOF measurement are presented.
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41.
  • Patronis, N., et al. (författare)
  • Status report of the n_TOF facility after the 2nd CERN long shutdown period
  • 2023
  • Ingår i: EPJ TECHNIQUES AND INSTRUMENTATION. - : Springer Nature. - 2195-7045. ; 10
  • Tidskriftsartikel (refereegranskat)abstract
    • During the second long shutdown period of the CERN accelerator complex (LS2, 2019-2021), several upgrade activities took place at the n_TOF facility. The most important have been the replacement of the spallation target with a next generation nitrogen-cooled lead target. Additionally, a new experimental area, at a very short distance from the target assembly (the NEAR Station) was established. In this paper, the core commissioning actions of the new installations are described. The improvement in the n_TOF infrastructure was accompanied by several detector development projects. All these upgrade actions are discussed, focusing mostly on the future perspectives of the n_TOF facility. Furthermore, some indicative current and future measurements are briefly reported.
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42.
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43.
  • Tagliente, G., et al. (författare)
  • The n_TOF facility at CERN
  • 2024
  • Ingår i: 16<sup>th</sup> Varenna Conference on Nuclear Reaction Mechanisms (NRM2023). - : EDP Sciences. - 9782759891245
  • Konferensbidrag (refereegranskat)abstract
    • The neutron Time-of-Flight facility (n_TOF) is an innovative facility operative since 2001 at CERN, with three experimental areas. In this paper the n_TOF facility will be described, together with the upgrade of the facility during the Long Shutdown 2 at CERN. The main features of the detectors used for capture fission cross section measurements will be presented with perspectives for the future measurements.
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44.
  • Aran, A., et al. (författare)
  • Evidence for local particle acceleration in the first recurrent galactic cosmic ray depression observed by Solar Orbiter : The ion event on 19 June 2020
  • 2021
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 656
  • Tidskriftsartikel (refereegranskat)abstract
    • Context. In mid-June 2020, the Solar Orbiter (SolO) mission reached its first perihelion at 0.51 au and started its cruise phase, with most of the in situ instruments operating continuously.Aims. We present the in situ particle measurements of the first proton event observed after the first perihelion obtained by the Energetic Particle Detector (EPD) suite on board SolO. The potential solar and interplanetary (IP) sources of these particles are investigated.Methods. Ion observations from similar to 20 keV to similar to 1 MeV are combined with available solar wind data from the Radio and Plasma Waves (RPW) instrument and magnetic field data from the magnetometer on board SolO to evaluate the energetic particle transport conditions and infer the possible acceleration mechanisms through which particles gain energy. We compare > 17-20 MeV ion count rate measurements for two solar rotations, along with the solar wind plasma data available from the Solar Wind Analyser (SWA) and RPW instruments, in order to infer the origin of the observed galactic cosmic ray (GCR) depressions.Results. The lack of an observed electron event and of velocity dispersion at various low-energy ion channels and the observed IP structure indicate a local IP source for the low-energy particles. From the analysis of the anisotropy of particle intensities, we conclude that the low-energy ions were most likely accelerated via a local second-order Fermi process. The observed GCR decrease on 19 June, together with the 51.8-1034.0 keV nuc(-1) ion enhancement, was due to a solar wind stream interaction region (SIR). The observation of a similar GCR decrease in the next solar rotation favours this interpretation and constitutes the first observation of a recurrent GCR decrease by SolO. The analysis of the recurrence times of this SIR suggests that it is the same SIR responsible for the He-4 events previously measured in April and May. Finally, we point out that an IP structure more complex than a common SIR cannot be discarded, mainly due to the lack of solar wind temperature measurements and the lack of a higher cadence of solar wind velocity observations.
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45.
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46.
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47.
  • Ge, R, et al. (författare)
  • Normative Modeling of Brain Morphometry Across the Lifespan Using CentileBrain: Algorithm Benchmarking and Model Optimization
  • 2023
  • Ingår i: bioRxiv : the preprint server for biology. - : Cold Spring Harbor Laboratory.
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Background: Normative modeling is a statistical approach to quantify the degree to which a particular individual-level measure deviates from the pattern observed in a normative reference population. When applied to human brain morphometric measures it has the potential to inform about the significance of normative deviations for health and disease. Normative models can be implemented using a variety of algorithms that have not been systematically appraised. Methods: To address this gap, eight algorithms were compared in terms of performance and computational efficiency using brain regional morphometric data from 37,407 healthy individuals (53% female; aged 3-90 years) collated from 87 international MRI datasets. Performance was assessed with the mean absolute error (MAE) and computational efficiency was inferred from central processing unit (CPU) time. The algorithms evaluated were Ordinary Least Squares Regression (OLSR), Bayesian Linear Regression (BLR), Generalized Additive Models for Location, Scale, and Shape (GAMLSS), Parametric Lambda, Mu, Sigma (LMS), Gaussian Process Regression (GPR), Warped Bayesian Linear Regression (WBLG), Hierarchical Bayesian Regression (HBR), and Multivariable Fractional Polynomial Regression (MFPR). Model optimization involved testing nine covariate combinations pertaining to acquisition features, parcellation software versions, and global neuroimaging measures (i.e., total intracranial volume, mean cortical thickness, and mean cortical surface area). Findings: Statistical comparisons across models at PFDR<0.05 indicated that the MFPR-derived sex- and region-specific models with nonlinear polynomials for age and linear effects of global measures had superior predictive accuracy; the range of the MAE of the models of regional subcortical volumes was 70-520 mm3 and the corresponding ranges for regional cortical thickness and regional cortical surface area were 0.09-0.26 mm and 24-560 mm2, respectively. The MFPR-derived models were also computationally more efficient with a CPU time below one second compared to a range of 2 seconds to 60 minutes for the other algorithms. The performance of all sex- and region-specific MFPR models plateaued at sample sizes exceeding 3,000 and showed comparable MAEs across distinct 10-year age-bins covering the human lifespan. Interpretation: These results provide an empirically benchmarked framework for normative modeling of brain morphometry that is useful for interpreting prior literature and supporting future study designs. The model and tools described here are freely available through CentileBrain (https://centilebrain.org/), a user-friendly web platform.
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48.
  • Gubinelli, F., et al. (författare)
  • Characterisation of functional deficits induced by AAV overexpression of alpha-synuclein in rats
  • 2023
  • Ingår i: Current Research in Neurobiology. - : Elsevier BV. - 2665-945X. ; 4
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: In the last decades different preclinical animal models of Parkinson's disease (PD) have been generated, aiming to mimic the progressive neuronal loss of midbrain dopaminergic (DA) cells as well as motor and non-motor impairment. Among all the available models, AAV-based models of human alpha-synuclein (h-aSYN) overexpression are promising tools for investigation of disease progression and therapeutic interventions. Objectives: The goal with this work was to characterise the impairment in motor and non-motor domains following nigrostriatal overexpression of h-aSYN and correlate the behavioural deficits with histological assessment of associated pathology. Methods: Intranigral injection of an AAV9 expressing h-aSYN was compared with untreated animals, 6-OHDA and AAV9 expressing either no transgene or GFP. The animals were assessed on a series of simple and complex behavioural tasks probing motor and non-motor domains. Post-mortem neuropathology was analysed using immunohistochemical methods. Results: Overexpression of h-aSYN led to progressive degeneration of DA neurons of the SN and axonal terminals in the striatum (STR). We observed extensive nigral and striatal pathology, resembling that of human PD brain, as well as the development of stable progressive deficit in simple motor tasks and in non-motor domains such as deficits in motivation and lateralised neglect. Conclusions: In the present work we characterized a rat model of PD that closely resembles human PD pathology at the histological and behavioural level. The correlation of cell loss with behavioural performance enables the selection of rats which can be used in neuroprotective or neurorestorative therapies.
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