| 1. |
- Aad, G, et al.
(författare)
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- 2015
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swepub:Mat__t
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| 2. |
- Abe, K., et al.
(författare)
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Neutron tagging following atmospheric neutrino events in a water Cherenkov detector
- 2022
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Ingår i: Journal of Instrumentation. - : Institute of Physics (IOP). - 1748-0221. ; 17:10
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Tidskriftsartikel (refereegranskat)abstract
- We present the development of neutron-tagging techniques in Super-Kamiokande IV using a neural network analysis. The detection efficiency of neutron capture on hydrogen is estimated to be 26%, with a mis-tag rate of 0.016 per neutrino event. The uncertainty of the tagging efficiency is estimated to be 9.0%. Measurement of the tagging efficiency with data from an Americium-Beryllium calibration agrees with this value within 10%. The tagging procedure was performed on 3,244.4 days of SK-IV atmospheric neutrino data, identifying 18,091 neutrons in 26,473 neutrino events. The fitted neutron capture lifetime was measured as 218 +/- 9 mu s.
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| 3. |
- Ambrosio, M, et al.
(författare)
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The MACRO detector at Gran Sasso
- 2002
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Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier. - 0168-9002 .- 1872-9576. ; 486:3, s. 663-707
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Tidskriftsartikel (refereegranskat)abstract
- MACRO was an experiment that ran in the Laboratori Nazionali del Gran Sasso from 1988 to 2000. Its principal goal was to observe magnetic monopoles or set significantly lower experimental flux limits than had been previously available in the velocity range from about beta = 10(-4) to unity. In addition it made a variety of other observations. Examples are: setting flux limits on other so far unobserved particles such as nuclearites and lightly ionizing particles, searching for WIMP annihilations in the Earth and the Sun and for neutrino bursts from stellar collapses in or near our Galaxy, and making measurements relevant to high energy muon and neutrino astronomy and of the flux of up-going muons as a function of nadir angle showing evidence for neutrino oscillations. The apparatus consisted of three principal types of detectors: liquid scintillator counters, limited streamer tubes, and nuclear track etch detectors. In addition, over part of its area it contained a transition radiation detector. The general design philosophy emphasized redundancy and complementarity. This paper describes the technical aspects of the complete MACRO detector, its operational performance, and the techniques used to calibrate it and verify its proper operation. It supplements a previously published paper which described the first portion of the detector that was built and operated. (C) 2002 Elsevier Science B.V. All rights reserved.
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| 4. |
- Ageron, M., et al.
(författare)
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ANTARES : The first undersea neutrino telescope
- 2011
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Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier. - 0168-9002 .- 1872-9576. ; 656:1, s. 11-38
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Tidskriftsartikel (refereegranskat)abstract
- The ANTARES Neutrino Telescope was completed in May 2008 and is the first operational Neutrino Telescope in the Mediterranean Sea. The main purpose of the detector is to perform neutrino astronomy and the apparatus also offers facilities for marine and Earth sciences. This paper describes the design, the construction and the installation of the telescope in the deep sea, offshore from Toulon in France. An illustration of the detector performance is given. (C) 2011 Elsevier B.V. All rights reserved.
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| 5. |
- Ageron, M., et al.
(författare)
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The ANTARES optical beacon system
- 2007
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Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier. - 0168-9002 .- 1872-9576. ; 578:3, s. 498-509
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Tidskriftsartikel (refereegranskat)abstract
- ANTARES is a neutrino telescope being deployed in the Mediterranean Sea. It consists of a three-dimensional array of photomultiplier tubes that can detect the Cherenkov light induced by charged particles produced in the interactions of neutrinos with the surrounding medium. High angular resolution can be achieved, in particular, when a muon is produced, provided that the Cherenkov photons are detected with sufficient timing precision. Considerations of the intrinsic time uncertainties stemming from the transit time spread in the photomultiplier tubes and the mechanism of transmission of light in sea water lead to the conclusion that a relative time accuracy of the order of 0.5 ns is desirable. Accordingly, different time calibration systems have been developed for the ANTARES telescope. In this article, a system based on Optical Beacons, a set of external and well-controlled pulsed light sources located throughout the detector, is described. This calibration system takes into account the optical properties of sea water, which is used as the detection volume of the ANTARES telescope. The design, tests, construction and first results of the two types of beacons, LED and laser-based, are presented. (C) 2007 Elsevier B.V. All rights reserved.
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| 6. |
- Aguilar, J. A., et al.
(författare)
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First results of the instrumentation line for the deep-sea ANTARES neutrino telescope
- 2006
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Ingår i: Astroparticle physics. - : Elsevier. - 0927-6505 .- 1873-2852. ; 26:4-5, s. 314-324
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Tidskriftsartikel (refereegranskat)abstract
- In 2005, the ANTARES Collaboration deployed and operated at a depth of 2500 m a so-called Mini Instrumentation Line equipped with Optical Modules (MILOM) at the ANTARES site. The various data acquired during the continuous operation from April to December 2005 of the MILOM confirm the satisfactory performance of the Optical Modules, their front-end electronics and readout system. as well as the calibration devices of the detector. The in situ measurement of the Optical Module time response yields a resolution better than 0.5 ns. The performance of the acoustic positioning system, which enables the spatial reconstruction of the ANTARES detector with a precision of about 10 cm, is verified. These results demonstrate that with the full ANTARES neutrino telescope the design angular resolution of better than 0.3 degrees can be realistically achieved.
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| 7. |
- Aguilar, J. A., et al.
(författare)
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The data acquisition system for the ANTARES neutrino telescope
- 2007
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Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier. - 0168-9002 .- 1872-9576. ; 570:1, s. 107-116
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Tidskriftsartikel (refereegranskat)abstract
- The ANTARES neutrino telescope is being constructed in the Mediterranean Sea. It consists of a large three-dimensional array of photo-multiplier tubes. The data acquisition system of the detector takes care of the digitisation of the photo-multiplier tube signals, data transport, data filtering, and data storage. The detector is operated using a control program interfaced with all elements. The design and the implementation of the data acquisition system are described. (c) 2006 Elsevier B.V. All rights reserved.
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| 8. |
- Ageron, M., et al.
(författare)
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Studies of a full-scale mechanical prototype line for the ANTARES neutrino telescope and tests of a prototype instrument for deep-sea acoustic measurements
- 2007
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Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier. - 0168-9002 .- 1872-9576. ; 581:3, s. 695-708
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Tidskriftsartikel (refereegranskat)abstract
- full-scale mechanical prototype line was deployed to a depth of 2500 m to test the leak tightness of the electronics containers and the pressure-resistant properties of an electromechanical cable under evaluation for use in the ANTARES deep-sea neutrino telescope. During a month-long immersion study, line parameter data were taken using miniature autonomous data loggers and shore-based optical time domain reflectometry. Details of the mechanical prototype line, the electromechanical cable and data acquisition are presented. Data taken during the immersion study revealed deficiencies in the pressure resistance of the electromechanical cable terminations at the entry points to the electronics containers. The improvements to the termination, which have been integrated into subsequent detection lines, are discussed. The line also allowed deep-sea acoustic measurements with a prototype hydrophone system. The technical setup of this system is described, and the first results of the data analysis are presented. (c) 2007 Elsevier B.V. All rights reserved.
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| 9. |
- Aglietta, M, et al.
(författare)
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The cosmic ray primary composition between 10(15) and 10(16) eV from Extensive Air Showers electromagnetic and TeV muon data
- 2004
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Ingår i: Astroparticle physics. - : Elsevier. - 0927-6505 .- 1873-2852. ; 20:6, s. 641-652
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Tidskriftsartikel (refereegranskat)abstract
- The cosmic ray primary composition in the energy range between 10(15) and 10(16) eV, i.e., around the "knee" of the primary spectrum, has been studied through the combined measurements of the EAS-TOP air shower array (2005 m a. s.l., 10(5) m(2) collecting area) and the MACRO underground detector (963 m.a.s.l., 3100 m w.e. of minimum rock overburden, 920 m(2) effective area) at the National Gran Sasso Laboratories. The used observables are the air shower size (N-c) measured by EAS-TOP and the muon number (N-mu) recorded by MACRO. The two detectors are separated on average by 1200 m of rock, and located at a respective zenith angle of about 30degrees. The energy threshold at the surface for muons reaching the MACRO depth is approximately 1.3 TeV. Such muons are produced in the early stages of the shower development and in a kinematic region quite different from the one relevant for the usual N-mu - N-e studies. The measurement leads to a primary composition becoming heavier at the knee of the primary spectrum, the knee itself resulting from the steepening of the spectrum of a primary light component (p, He) of Deltay = 0.7 +/- 0.4 at E-0 similar to 4 x 10(15) eV. The result confirms the ones reported from the observation of the low energy muons at the surface (typically in the GeV energy range), showing that the conclusions do not depend on the production region kinematics. Thus, the hadronic interaction model used (CORSIKA/QGSJET) provides consistent composition results from data related to secondaries produced in a rapidity region exceeding the central one. Such an evolution of the composition in the knee region supports the "standard" galactic acceleration/propagation models that imply rigidity dependent breaks of the different components.. and therefore breaks occurring at lower energies in the spectra of the light nuclei. (C) 2003 Elsevier B.V. All rights reserved.
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| 10. |
- Aglietta, M, et al.
(författare)
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The cosmic ray proton, helium and CNO fluxes in the 100 TeV energy region from TeV muons and EAS atmospheric Cherenkov light observations of MACRO and EAS-TOP
- 2004
-
Ingår i: Astroparticle physics. - : Elsevier. - 0927-6505 .- 1873-2852. ; 21:3, s. 223-240
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Tidskriftsartikel (refereegranskat)abstract
- The primary cosmic ray (CR) proton, helium and CNO fluxes in the energy range 80-300 TeV are studied at the National Gran Sasso Laboratories by means of EAS-TOP (Campo Imperatore, 2005 m a.s.l.) and MACRO (deep underground, 3100 m w.e., the surface energy threshold for a muon reaching the detector being E-mu(th) approximate to 1.3 TeV). The measurement is based on: (a) the selection of primaries based on their energy/nucleon (i.e., with energy/nucleon sufficient to produce a muon with energy larger than 1.3 TeV) and the reconstruction of the shower geometry by means of the muons recorded by MACRO in the deep underground laboratories; (b) the detection of the associated atmospheric Cherenkov light (C.l.) signals by means of the C.l. detector of EAS-TOP. The C.l. density at core distance r > 100 m is directly related to the total primary energy E-0. Proton and helium ("p + He") and proton, helium and CNO ("p + He + CNO") primaries are thus selected at E-0 approximate to 80 TeV, and at E-0 similar or equal to 250 TeV, respectively. Their flux is measured: J(p+He)(80 TeV) = (1.8 +/- 0.4) x 10(-6) m(-1)-s(-1) sr(-1) TeV-1, and J(p+He+CNO)(250 TeV) = (1.1 +/- 0.3) x 10(-7) m(-2)-s(-1) sr(-1) TeV-1, their relative weights being J(p+He)(J(p+He+CNO)) over bar (250 TeV) = 0.78 +/- 0.17. By using the measurements of the proton spectrum obtained from the direct experiments and hadron flux data in the atmosphere, we obtain for the relative weights of the three components at 250 TeV: J(p) : J(He) : J(CNO) = (0.20 +/- 0.08) : (0.58 +/- 0.19) : (0.22 +/- 0.17). This corresponds to the dominance of helium over proton primaries at 100-1000 TeV, and a possible non-negligible contribution from CNO. The lateral distribution of Cherenkov light in Extensive Air Showers (EASs), which is related to the rate of energy deposit of the primary in the atmosphere, is measured for a selected proton and helium primary beam, and good agreement is found when compared with the one calculated with the CORSIKA/QGSJET simulation model. (C) 2004 Elsevier B.V. All rights reserved.
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| 11. |
- Ambrosio, M, et al.
(författare)
-
Matter effects in upward-going muons and sterile neutrino oscillations
- 2001
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Ingår i: Physics Letters B. - : Elsevier. - 0370-2693 .- 1873-2445. ; 517:1-2, s. 59-66
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Tidskriftsartikel (refereegranskat)abstract
- The angular distribution of upward-going muons produced by atmospheric neutrinos in the rock below the MACRO detector shows anomalies in good agreement with two flavor nu (mu) --> nu (tau) oscillations with maximum mixing and Deltam(2) around 0.0024 eV(2). Exploiting the dependence of magnitude of the matter effect on oscillation channel, and using a set of 809 upward-going muons observed in MACRO, we show that the two flavor nu (mu) --> nu (s) oscillation is disfavored with 99% C.L. with respect to nu (mu) --> nu (tau). (C) 2001 Elsevier Science B.V. All rights reserved.
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| 12. |
- Ambrosio, M, et al.
(författare)
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Muon energy estimate through multiple scattering with the MACRO detector
- 2002
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Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - 0168-9002 .- 1872-9576. ; 492:3, s. 376-386
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Tidskriftsartikel (refereegranskat)abstract
- Muon energy measurement represents an important issue for any experiment addressing neutrino-induced up-going muon studies. Since the neutrino oscillation probability depends on the neutrino energy, a measurement of the muon energy adds an important piece of information concerning the neutrino system. We show in this paper how the MACRO limited streamer tube system can be operated in drift mode by using the TDCs included in the QTPs, an electronics designed for magnetic monopole search. An improvement of the space resolution is obtained, through an analysis of the multiple scattering of muon tracks as they pass through our detector. This information can be used further to obtain an estimate of the energy of muons crossing the detector. Here we present the results of two dedicated tests, performed at CERN PS-T9 and SPS-X7 beam lines, to provide a full check of the electronics and to exploit the feasibility of such a multiple scattering analysis. We show that by using a neural network approach, we are able to reconstruct the muon energy for E-mu < 40 GeV. The test beam data provide an absolute energy calibration, which allows us to apply this method to MACRO data. (C) 2002 Elsevier Science B.V. All rights reserved.
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| 13. |
- Ambrosio, M, et al.
(författare)
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Search for the sidereal and solar diurnal modulations in the total MACRO muon data set
- 2003
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Ingår i: Physical Review D. Particles and fields. - : American Physical Society. - 0556-2821 .- 1089-4918. ; 67:4
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Tidskriftsartikel (refereegranskat)abstract
- We have analyzed 44.3M single muons collected by MACRO from 1991 through 2000 in 2145 live days of operation. We have searched for the solar diurnal, apparent sidereal, and pseudosidereal modulation of the underground muon rate by computing hourly deviations of the muon rate from 6 month averages. We find evidence for statistically significant modulations with the solar diurnal and the sidereal periods. The amplitudes of these modulations are <0.1%, and are at the limit of the detector statistics. The pseudosidereal modulation is not statistically significant. The solar diurnal modulation is due to the daily atmospheric temperature variations at 20 km, the altitude of primary cosmic ray interactions with the atmosphere; MACRO is the deepest experiment to report this result. The sidereal modulation is in addition to the expected Compton-Getting modulation due to solar system motion relative to the local standard of rest; it represents motion of the solar system with respect to the galactic cosmic rays toward the galactic plane.
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| 14. |
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| 15. |
- Ambrosio, M, et al.
(författare)
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A combined analysis technique for the search for fast magnetic monopoles with the MACRO detector
- 2002
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Ingår i: Astroparticle physics. - : Elsevier. - 0927-6505 .- 1873-2852. ; 18:1, s. 27-41
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Tidskriftsartikel (refereegranskat)abstract
- We describe a search method for fast moving (beta = v/c > 5 x 10(-3)) magnetic monopoles using simultaneously the scintillator, streamer tube and track-etch subdetectors of the MACRO apparatus. The first two subdetectors are used primarily for the identification of candidates while the track-etch one is used as the final tool for their rejection or confirmation. Using this technique, a first sample of more than two-years of data has been analyzed without any evidence of a magnetic monopole. We set a 90% CL upper limit to the local monopole flux of 1.5 x 10(-15) cm(-2) s(-1) sr(-1) in the velocity range 5 x 10(-3) less than or equal to beta less than or equal to 0.99 and for nucleon decay catalysis cross-section smaller than similar to1 mb (C) 2002 Elsevier Science B.V. All rights reserved.
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| 16. |
- Ambrosio, M, et al.
(författare)
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Atmospheric neutrino oscillations from upward throughgoing muon multiple scattering in MACRO
- 2003
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Ingår i: Physics Letters B. - 0370-2693 .- 1873-2445. ; 566:1-2, s. 35-44
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Tidskriftsartikel (refereegranskat)abstract
- The energy of atmospheric neutrinos detected by MACRO was estimated using multiple Coulomb scattering of upward throughgoing muons. This analysis allows a test of atmospheric neutrino oscillations, relying on the distortion of the muon energy distribution. These results have been combined with those coming from the upward throughgoing muon angular distribution only. Both analyses are independent of the neutrino flux normalization and provide strong evidence, above the for level, in favour of neutrino oscillations. (C) 2003 Published by Elsevier B.V.
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| 17. |
- Ambrosio, M, et al.
(författare)
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Final results of magnetic monopole searches with the MACRO experiment
- 2002
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Ingår i: European Physical Journal C. - : Springer. - 1434-6044 .- 1434-6052. ; 25:4, s. 511-522
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Tidskriftsartikel (refereegranskat)abstract
- We present the final results obtained by the MACRO experiment in the search for GUT magnetic monopoles in the penetrating cosmic radiation, for the range 4 x 10(-5) < 3 < 1. Several searches with all the MACRO sub-detectors (i.e. scintillation counters, limited streamer tubes and nuclear track detectors) were performed, both in stand alone and combined ways. No candidates were detected and a 90% Confidence Level (C.L.) upper limit to the local magnetic monopole flux was set at the level of 1.4 x 10(-16) cm(-2) s(-1) sr(-1). This result is the first experimental limit obtained in direct searches which is well below the Parker bound in the whole 3 range in which GUT magnetic monopoles are,expected.
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| 18. |
- Ambrosio, M, et al.
(författare)
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Measurement of the residual energy of muons in the Gran Sasso underground laboratories
- 2003
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Ingår i: Astroparticle physics. - : Elsevier. - 0927-6505 .- 1873-2852. ; 19:3, s. 313-328
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Tidskriftsartikel (refereegranskat)abstract
- The MACRO detector was located in the Hall B of the Gran Sasso underground laboratories under an average rock overburden of 3700 hg/cm(2). A transition radiation detector composed of three identical modules, covering a total horizontal area of 36 m(2), was installed inside the empty upper part of the detector in order to measure the residual energy of muons. This paper presents the measurement of the residual energy of single and double muons crossing the apparatus. Our data show that double muons are more energetic than single ones. This measurement is performed over a standard rock depth range from 3000 to 6500 hg/cm(2). (C) 2002 Elsevier Science B.V. All rights reserved.
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| 19. |
- Ambrosio, M, et al.
(författare)
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Measurements of atmospheric muon neutrino oscillations, global analysis of the data collected with MACRO detector
- 2004
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Ingår i: European Physical Journal C. - : Springer. - 1434-6044 .- 1434-6052. ; 36:3, s. 323-339
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Tidskriftsartikel (refereegranskat)abstract
- The final analysis of atmospheric neutrino events collected with the MACRO detector is presented. Three different classes of events, generated by neutrinos in different energy ranges, are studied looking at rates, angular distributions and estimated energies. The results are consistent for all the subsamples and indicate a flux deficit that depends on energy and path - length of neutrinos. The no - oscillation hypothesis is excluded at similar to 5sigma, while the hypothesis of nu(mu) --> nu(tau) oscillation gives a satisfactory description of all data. The parameters with highest probability in a two flavor scenario are sin(2) 2theta(m) = 1 and Deltam(2) = 0.0023 eV(2). This result is independent of the absolute normalization of the atmospheric neutrino fluxes. The data can also be used to put experimental constrain on this normalization.
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| 20. |
- Ambrosio, M, et al.
(författare)
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Moon and Sun shadowing effect in the MACRO detector
- 2003
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Ingår i: Astroparticle physics. - : Elsevier. - 0927-6505 .- 1873-2852. ; 20:2, s. 145-156
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Tidskriftsartikel (refereegranskat)abstract
- Using data collected by the MACRO experiment from 1989 to the end of its operations in 2000, we have studied in the underground muon flux the shadowing. effects due to both the Moon and the Sun. We have observed the shadow cast by the Moon at its apparent position with a significance of 6.5sigma. The Moon shadowing effect has been used to verify the pointing capability of the detector and to determine the instrument resolution for the search of muon excesses from any direction of the celestial sphere. The dependence of the effect on the geomagnetic field is clearly shown by splitting the data sample in day and night observations. The Sun shadow, observed with a significance of 4.6sigma is displaced by about 0.6degrees from its apparent position. In this case however the explanation resides in the configuration of the Solar and Interplanetary Magnetic Fields, which affect the propagation of cosmic ray particles between the Sun, and the Earth. The displacement of the Sun shadow with respect to the real Sun position has been used to establish an upper limit on the antimatter flux in cosmic rays of about 48% at 68% c.l. and primary energies of about 20 TeV. (C) 2003 Elsevier B.V. All rights reserved.
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| 21. |
- Ambrosio, M, et al.
(författare)
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Search for cosmic ray sources using muons detected by the MACRO experiment
- 2003
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Ingår i: Astroparticle physics. - : Elsevier. - 0927-6505 .- 1873-2852. ; 18:6, s. 615-627
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Tidskriftsartikel (refereegranskat)abstract
- The MACRO underground detector at Gran Sasso Laboratory recorded 60 million secondary cosmic ray muons from February 1989 until December 2000. Different techniques were used to analyze this sample in search for density excesses from astrophysical point-like sources. No evidence for DC excesses for any source in an all-sky survey is reported. In addition, searches for muon excess correlated with the known binary periods of Cygnus X-3 and Hercules X-1, and searches for statistically significant bursting episodes from known gamma-ray sources are also proved negative. (C) 2002 Elsevier Science B.V. All rights reserved.
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| 22. |
- Ambrosio, M, et al.
(författare)
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Search for diffuse neutrino flux from astrophysical sources with MACRO
- 2003
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Ingår i: Astroparticle physics. - : Elsevier. - 0927-6505 .- 1873-2852. ; 19:1, s. 1-13
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Tidskriftsartikel (refereegranskat)abstract
- Many galactic and extragalactic astrophysical sources are currently considered promising candidates as high-energy neutrino emitters. Astrophysical neutrinos can be detected as upward-going muons produced in charged-current interactions with the medium surrounding the detector. The expected neutrino fluxes from various models start to dominate on the atmospheric neutrino background at neutrino energies above some tens of TeV. We present the results of a search for an excess of high-energy upward-going muons among the sample of data collected by MACRO during similar to5.8 years of effective running time. No significant evidence for this signal was found. As a consequence, an upper limit on the flux of upward-going muons from high-energy neutrinos was set at the level of 1.7 x 10(-14) cm(-2) s(-1) sr(-1). The corresponding upper limit for the diffuse neutrino flux was evaluated assuming a neutrino power law spectrum. Our result was compared with theoretical predictions and upper limits from other experiments. (C) 2002 Elsevier Science B.V. All rights reserved.
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| 23. |
- Ambrosio, M, et al.
(författare)
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Search for nucleon decays induced by GUT magnetic monopoles with the MACRO experiment
- 2002
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Ingår i: European Physical Journal C. - : Springer. - 1434-6044 .- 1434-6052. ; 26:2, s. 163-172
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Tidskriftsartikel (refereegranskat)abstract
- The interaction of a Grand Unification Magnetic Monopole with a nucleon can lead to a barion-number violating process in which the nucleon decays into a lepton and one or more mesons (catalysis of nucleon decay). In this paper we report an experimental study of the effects of a catalysis process in the MACRO detector. Using a dedicated analysis we obtain new magnetic monopole (MM) flux upper limits at the level of similar to 3 (.) 10(-16) cm(-2) s(-1) sr(-1) for 1.1(.) 10(-4) less than or equal to \beta\ less than or equal to 5 (.) 10(-3), based on the search for catalysis events in the MACRO data. We also analyze the dependence of the MM flux limit on the catalysis cross section.
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| 24. |
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| 25. |
- Togo, V, et al.
(författare)
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Calibrations of CR39 and Makrofol nuclear track detectors and search for exotic particles
- 2003
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Ingår i: Nuclear physics B, Proceedings supplements. - : Elsevier. - 0920-5632 .- 1873-3832. ; 125, s. 217-221
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Tidskriftsartikel (refereegranskat)abstract
- We present the final results of the search for exotic massive particles in the cosmic radiation performed with the MACRO underground experiment. Magnetic monopoles and nuclearites flux upper limits obtained with the CR39 nuclear track subdetector, the scintillation and streamer tube subdetectors are given. Searches at high altitude with the SLIM experiment are in progress.
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| 26. |
- Kotmayer, L, et al.
(författare)
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Landscape of BCL2 Resistance Mutations in a Real-World Cohort of Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia Treated with Venetoclax
- 2023
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Ingår i: International journal of molecular sciences. - : MDPI AG. - 1422-0067. ; 24:6
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Tidskriftsartikel (refereegranskat)abstract
- The oral, highly selective Bcl2 inhibitor venetoclax has substantially improved the therapeutic landscape of chronic lymphocytic leukemia (CLL). Despite the remarkable response rates in patients with relapsed/refractory (R/R) disease, acquired resistance is the leading cause of treatment failure, with somatic BCL2 mutations being the predominant genetic drivers underpinning venetoclax resistance. To assess the correlation between disease progression and the most common BCL2 mutations G101V and D103Y, sensitive (10−4) screening for the most common BCL2 mutations G101V and D103Y was performed in 67 R/R CLL patients during venetoclax single-agent or venetoclax–rituximab combination therapy. With a median follow-up time of 23 months, BCL2 G101V and D103Y were detected in 10.4% (7/67) and 11.9% (8/67) of the cases, respectively, with four patients harboring both resistance mutations. Ten out of eleven patients carrying BCL2 G101V and/or D103Y experienced relapse during the follow-up period, representing 43.5% of the cases (10/23) showing clinical signs of disease progression. All BCL2 G101V or D103Y variants were detected in patients receiving venetoclax as a continuous single-agent treatment while these mutations were not observed during or after fixed-duration venetoclax therapy. Targeted ultra-deep sequencing of BCL2 uncovered three additional variants in four patient samples obtained at relapse, suggesting convergent evolution and implying a cooperating role of BCL2 mutations in driving venetoclax resistance. This cohort is the largest R/R CLL patient population reported to date in which BCL2 resistance mutations were investigated. Our study demonstrates the feasibility and clinical value of sensitive screening for BCL2 resistance mutations in R/R CLL.
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| 27. |
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