| 1. |
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| 2. |
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| 3. |
- Ederle, Joerg, et al.
(author)
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Carotid artery stenting compared with endarterectomy in patients with symptomatic carotid stenosis (International Carotid Stenting Study): an interim analysis of a randomised controlled trial
- 2010
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In: The Lancet. - 1474-547X. ; 375:9719, s. 985-997
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Journal article (peer-reviewed)abstract
- Background Stents are an alternative treatment to carotid endarterectomy for symptomatic carotid stenosis, but previous trials have not established equivalent safety and efficacy. We compared the safety of carotid artery stenting with that of carotid endarterectomy. Methods The International Carotid Stenting Study (ICSS) is a multicentre, international, randomised controlled trial with blinded adjudication of outcomes. Patients with recently symptomatic carotid artery stenosis were randomly assigned in a 1:1 ratio to receive carotid artery stenting or carotid endarterectomy. Randomisation was by telephone call or fax to a central computerised service and was stratified by centre with minimisation for sex, age, contralateral occlusion, and side of the randomised artery. Patients and investigators were not masked to treatment assignment. Patients were followed up by independent clinicians not directly involved in delivering the randomised treatment. The primary outcome measure of the trial is the 3-year rate of fatal or disabling stroke in any territory, which has not been analysed yet. The main outcome measure for the interim safety analysis was the 120-day rate of stroke, death, or procedural myocardial infarction. Analysis was by intention to treat (ITT). This study is registered, number ISRCTN25337470. Findings The trial enrolled 1713 patients (stenting group, n=855; endarterectomy group, n=858). Two patients in the stenting group and one in the endarterectomy group withdrew immediately after randomisation, and were not included in the ITT analysis. Between randomisation and 120 days, there were 34 (Kaplan-Meier estimate 4.0%) events of disabling stroke or death in the stenting group compared with 27 (3.2%) events in the endarterectomy group (hazard ratio [HR] 1.28, 95% CI 0.77-2.11). The incidence of stroke, death, or procedural myocardial infarction was 8.5% in the stenting group compared with 5.2% in the endarterectomy group (72 vs 44 events; HR 1.69, 1.16-2.45, p=0.006), Risks of any stroke (65 vs 35 events; HR 1.92, 1.27-2.89) and all-cause death (19 vs seven events; HR 2.76, 1.16-6.56) were higher in the stenting group than in the endarterectomy group. Three procedural myocardial infarctions were recorded in the stenting group, all of which were fatal, compared with four, all non-fatal, in the endarterectomy group. There was one event of cranial nerve palsy in the stenting group compared with 45 in the endarterectomy group. There were also fewer haematomas of any severity in the stenting group than in the endarterectomy group (31 vs 50 events; p=0.0197). Interpretation Completion of long-term follow-up is needed to establish the efficacy of carotid artery stenting compared with endarterectomy. In the meantime, carotid endarterectomy should remain the treatment of choice for patients suitable for surgery.
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| 4. |
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| 5. |
- Adriani, O., et al.
(author)
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Design of an Antimatter Large Acceptance Detector In Orbit (ALADInO)
- 2022
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In: Instruments. - : MDPI AG. - 2410-390X. ; 6:2
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Journal article (peer-reviewed)abstract
- A new generation magnetic spectrometer in space will open the opportunity to inves-tigate the frontiers in direct high-energy cosmic ray measurements and to precisely measure the amount of the rare antimatter component in cosmic rays beyond the reach of current missions. We propose the concept for an Antimatter Large Acceptance Detector In Orbit (ALADInO), designed to take over the legacy of direct measurements of cosmic rays in space performed by PAMELA and AMS-02. ALADInO features technological solutions conceived to overcome the current limi-tations of magnetic spectrometers in space with a layout that provides an acceptance larger than 10 m2 sr. A superconducting magnet coupled to precision tracking and time-of-flight systems can provide the required matter–antimatter separation capabilities and rigidity measurement resolution with a Maximum Detectable Rigidity better than 20 TV. The inner 3D-imaging deep calorimeter, designed to maximize the isotropic acceptance of particles, allows for the measurement of cosmic rays up to PeV energies with accurate energy resolution to precisely measure features in the cosmic ray spectra. The operations of ALADInO in the Sun–Earth L2 Lagrangian point for at least 5 years would enable unique revolutionary observations with groundbreaking discovery poten-tials in the field of astroparticle physics by precision measurements of electrons, positrons, and antiprotons up to 10 TeV and of nuclear cosmic rays up to PeV energies, and by the possible unam-biguous detection and measurement of low-energy antideuteron and antihelium components in cosmic rays.
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| 6. |
- Marconi, A., et al.
(author)
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ANDES, the high resolution spectrograph for the ELT : science case, baseline design and path to construction
- 2022
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In: GROUND-BASED AND AIRBORNE INSTRUMENTATION FOR ASTRONOMY IX. - : SPIE - International Society for Optical Engineering. - 9781510653504 - 9781510653498
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Conference paper (peer-reviewed)abstract
- The first generation of ELT instruments includes an optical-infrared high resolution spectrograph, indicated as ELT-HIRES and recently christened ANDES (ArmazoNes high Dispersion Echelle Spectrograph). ANDES consists of three fibre-fed spectrographs (UBV, RIZ, YJH) providing a spectral resolution of similar to 100,000 with a minimum simultaneous wavelength coverage of 0.4-1.8 mu m with the goal of extending it to 0.35-2.4 mu m with the addition of a K band spectrograph. It operates both in seeing- and diffraction-limited conditions and the fibre-feeding allows several, interchangeable observing modes including a single conjugated adaptive optics module and a small diffraction-limited integral field unit in the NIR. Its modularity will ensure that ANDES can be placed entirely on the ELT Nasmyth platform, if enough mass and volume is available, or partly in the Coude room. ANDES has a wide range of groundbreaking science cases spanning nearly all areas of research in astrophysics and even fundamental physics. Among the top science cases there are the detection of biosignatures from exoplanet atmospheres, finding the fingerprints of the first generation of stars, tests on the stability of Nature's fundamental couplings, and the direct detection of the cosmic acceleration. The ANDES project is carried forward by a large international consortium, composed of 35 Institutes from 13 countries, forming a team of more than 200 scientists and engineers which represent the majority of the scientific and technical expertise in the field among ESO member states.
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| 7. |
- Tinetti, Giovanna, et al.
(author)
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The EChO science case
- 2015
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In: Experimental astronomy. - : Springer Science and Business Media LLC. - 0922-6435 .- 1572-9508. ; 40:2-3, s. 329-391
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Journal article (peer-reviewed)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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| 8. |
- Glasbey, JC, et al.
(author)
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- 2021
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swepub:Mat__t
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| 9. |
- Tabiri, S, et al.
(author)
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- 2021
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swepub:Mat__t
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| 10. |
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| 11. |
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| 12. |
- Toppi, M., et al.
(author)
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Measurement of fragmentation cross sections of C-12 ions on a thin gold target with the FIRST apparatus
- 2016
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In: Physical Review C. - 2469-9985 .- 2469-9993. ; 93:6
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Journal article (peer-reviewed)abstract
- A detailed knowledge of the light ions interaction processes with matter is of great interest in basic and applied physics. As an example, particle therapy and space radioprotection require highly accurate fragmentation cross-section measurements to develop shielding materials and estimate acute and late health risks for manned missions in space and for treatment planning in particle therapy. The Fragmentation of Ions Relevant for Space and Therapy experiment at the Helmholtz Center for Heavy Ion research (GSI) was designed and built by an international collaboration from France, Germany, Italy, and Spain for studying the collisions of a C-12 ion beam with thin targets. The collaboration's main purpose is to provide the double-differential cross-section measurement of carbon-ion fragmentation at energies that are relevant for both tumor therapy and space radiation protection applications. Fragmentation cross sections of light ions impinging on a wide range of thin targets are also essential to validate the nuclear models implemented in MC simulations that, in such an energy range, fail to reproduce the data with the required accuracy. This paper presents the single differential carbon-ion fragmentation cross sections on a thin gold target, measured as a function of the fragment angle and kinetic energy in the forward angular region (theta less than or similar to 6 degrees), aiming to provide useful data for the benchmarking of the simulation softwares used in light ions fragmentation applications. The C-12 ions used in the measurement were accelerated at the energy of 400 MeV/nucleon by the SIS (heavy ion synchrotron) GSI facility.
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| 13. |
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| 14. |
- Bravo, L, et al.
(author)
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- 2021
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swepub:Mat__t
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| 15. |
- Golosio, B., et al.
(author)
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The FIRST experiment for nuclear fragmentation measurements at GSI
- 2011
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In: Nuclear Science Symposium and Medical Imaging Conference (NSS/MIC), 2011 IEEE. ; , s. 2277-2280
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Conference paper (peer-reviewed)abstract
- Nuclear fragmentation processes are relevant in different fields of physics concerning both basic research and applications. FIRST (Fragmentation of Ions Relevant for Space and Therapy) is an experiment aimed at the measurement of double differential cross sections (DDCS), with respect to kinetic energy and scattering polar angle, of nuclear fragmentation processes relevant for hadron therapy and for space radiation protection applications, in the energy range between 100 and 1000 MeV/u. The experiment was mounted at the GSI laboratories of Darmstadt, in Germany. A first data taking was performed in August 2011, using 400 MeV/u 12C on carbon and gold targets. In this work we present a description of the experimental apparatus and some figures from the data acquisition and from the preliminary work on data analysis
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| 16. |
- Marconi, A., et al.
(author)
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EELT-HIRES the high-resolution spectrograph for the E-ELT
- 2016
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In: GROUND-BASED AND AIRBORNE INSTRUMENTATION FOR ASTRONOMY VI. - : SPIE. - 9781510601963
-
Conference paper (peer-reviewed)abstract
- The first generation of E-ELT instruments will include an optical infrared High Resolution Spectrograph, conventionally indicated as EELT-HIRES, which will be capable of providing unique breakthroughs in the fields of exoplanets, star and planet formation, physics and evolution of stars and galaxies, cosmology and fundamental physics. A 2-year long phase A study for EELT-HIRES has just started and will be performed by a consortium composed of institutes and organisations from Brazil, Chile, Denmark, France, Germany, Italy, Poland, Portugal, Spain, Sweden, Switzerland and United Kingdom. In this paper we describe the science goals and the preliminary technical concept for EELT-HIRES which will be developed during the phase A, as well as its planned development and consortium organisation during the study.
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| 17. |
- Marconi, Alessandro, et al.
(author)
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ELT-HIRES, the high resolution spectrograph for the ELT : Phase A study and path to construction
- 2020
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In: Ground-based and Airborne Instrumentation for Astronomy VIII. - : SPIE - International Society for Optical Engineering. - 9781510636828 - 9781510636811
-
Conference paper (peer-reviewed)abstract
- HIRES is the high-resolution spectrograph of the European Extremely Large Telescope at optical and near-infrared wavelengths. It consists of three fibre-fed spectrographs providing a wavelength coverage of 0.4-1.8 µm (goal 0.35-2.4 µm) at a spectral resolution of 100,000. The fibre-feeding allows HIRES to have several, interchangeable observing modes including a SCAO module and a small diffraction-limited IFU in the NIR. Therefore, it will be able to operate both in seeing- and diffraction-limited modes. Its modularity will ensure that HIRES can be placed entirely on the Nasmyth platform, if enough mass and volume is available, or part on the Nasmyth and part in the Coud`e room. ELT-HIRES has a wide range of science cases spanning nearly all areas of research in astrophysics and even fundamental physics. Among the top science cases there are the detection of biosignatures from exoplanet atmospheres, finding the fingerprints of the first generation of stars (PopIII), tests on the stability of Nature’s fundamental couplings, and the direct detection of the cosmic acceleration. The HIRES consortium is composed of more than 30 institutes from 14 countries, forming a team of more than 200 scientists and engineers.
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| 18. |
- Pleskac, R., et al.
(author)
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The FIRST experiment at GSI
- 2012
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In: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 678, s. 130-138
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Journal article (peer-reviewed)abstract
- The FIRST (Fragmentation of Ions Relevant for Space and Therapy) experiment at the SIS accelerator of GSl laboratory in Darmstadt has been designed for the measurement of ion fragmentation crosssections at different angles and energies between 100 and 1000 MeV/nucleon. Nuclear fragmentation processes are relevant in several fields of basic research and applied physics and are of particular interest for tumor therapy and for space radiation protection applications. The start of the scientific program of the FIRST experiment was on summer 2011 and was focused on the measurement of 400 MeV/nucleon C-12 beam fragmentation on thin (8 mm) graphite target. The detector is partly based on an already existing setup made of a dipole magnet (ALADiN). a time projection chamber (TP-MUSIC IV), a neutron detector (LAND) and a time of flight scintillator system (TOFWALL). This pre-existing setup has been integrated with newly designed detectors in the Interaction Region, around the carbon target placed in a sample changer. The new detectors are a scintillator Start Counter, a Beam Monitor drift chamber, a silicon Vertex Detector and a Proton Tagger scintillator system optimized for the detection of light fragments emitted at large angles. In this paper we review the experimental setup, then we present the simulation software, the data acquisition system and finally the trigger strategy of the experiment.
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| 19. |
- Rescigno, R., et al.
(author)
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Performance of the reconstruction algorithms of the FIRST experiment pixel sensors vertex detector
- 2014
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In: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 767, s. 34-40
-
Journal article (peer-reviewed)abstract
- Hadrontherapy treatments use charged particles (e.g. protons and carbon ions) to treat tumors. During a therapeutic treatment with carbon ions, the beam undergoes nuclear fragmentation processes giving rise to significant yields of secondary charged particles. An accurate prediction of these production rates is necessary to estimate precisely the dose deposited into the tumours and the surrounding healthy tissues. Nowadays, a limited set of double differential carbon fragmentation cross-section is available. Experimental data are necessary to benchmark Monte Carlo simulations for their use in hadrontherapy. The purpose of the FIRST experiment is to study nuclear fragmentation processes of ions with kinetic energy in the range from 100 to 1000 MeV/u. Tracks are reconstructed using information from a pixel silicon detector based on the CMOS technology. The performances achieved using this device for hadrontherapy purpose are discussed. For each reconstruction step (clustering, tracking and vertexing), different methods are implemented. The algorithm performances and the accuracy on reconstructed observables are evaluated on the basis of simulated and experimental data.
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| 20. |
- Sieberts, SK, et al.
(author)
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Crowdsourced assessment of common genetic contribution to predicting anti-TNF treatment response in rheumatoid arthritis
- 2016
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In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7, s. 12460-
-
Journal article (peer-reviewed)abstract
- Rheumatoid arthritis (RA) affects millions world-wide. While anti-TNF treatment is widely used to reduce disease progression, treatment fails in ∼one-third of patients. No biomarker currently exists that identifies non-responders before treatment. A rigorous community-based assessment of the utility of SNP data for predicting anti-TNF treatment efficacy in RA patients was performed in the context of a DREAM Challenge (http://www.synapse.org/RA_Challenge). An open challenge framework enabled the comparative evaluation of predictions developed by 73 research groups using the most comprehensive available data and covering a wide range of state-of-the-art modelling methodologies. Despite a significant genetic heritability estimate of treatment non-response trait (h2=0.18, P value=0.02), no significant genetic contribution to prediction accuracy is observed. Results formally confirm the expectations of the rheumatology community that SNP information does not significantly improve predictive performance relative to standard clinical traits, thereby justifying a refocusing of future efforts on collection of other data.
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| 21. |
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| 22. |
- Di Marcantonio, P., et al.
(author)
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ANDES, the high resolution spectrograph for the ELT : project management and system engineering approaches for mastering its preliminary design phase
- 2022
-
In: MODELING, SYSTEMS ENGINEERING, AND PROJECT MANAGEMENT FOR ASTRONOMY X. - : SPIE - International Society for Optical Engineering. - 9781510653566 - 9781510653559
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Conference paper (other academic/artistic)abstract
- At the end of 2021, the ESO council approved the start of the construction phase for a High Resolution Spectrograph for the ELT, formerly known as ELT-HIRES, renamed recently as ANDES (ArmazoNes high Dispersion Echelle Spectrograph). The current initial schedule foresees a 9-years development aimed to bring the instrument on-sky soon after the first-generation ELT instruments. ANDES combines high spectral resolution (up to 100,000), wide spectral range (0.4 mu m to 1.8 mu m with a goal from 0.35 mu m to 2.4 mu m) and extreme stability in wavelength calibration accuracy (better than 0.02 m/s rms over a 10-year period in a selected wavelength range) with massive optical collecting power of the ELT thus enabling to achieve possible breakthrough groundbreaking scientific discoveries. The main science cases cover a possible detection of life signatures in exoplanets, the study of the stability of Nature's physical constants along the universe lifetime and a first direct measurement of the cosmic acceleration. The reference design of this instrument in its extended version (with goals included) foresees 4 spectrographic modules fed by fibers, operating in seeing and diffraction limited (adaptive optics assisted) mode carried out by an international consortium composed by 24 institutes from 13 countries which poses big challenges in several areas. In this paper we will describe the approach we intend to pursue to master management and system engineering aspects of this challenging instrument focused mainly on the preliminary design phase, but looking also ahead towards its final construction.
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| 23. |
- Lundquist, J., et al.
(author)
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The PAMELA Calorimeter Identification Capabilities
- 2005
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In: Proceedings of the 29th International Cosmic Ray Conference, vol 3:OG1. ; , s. 305-308
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Conference paper (peer-reviewed)abstract
- A silicon-tungsten imaging calorimeter has been designed, built and successfully integrated in the PAMELA satellite-bome apparatus. The main physics task of the experiment is the measurement of the flux of antiprotons, positrons and light nuclei in the cosmic radiation. The purpose of the calorimeter is to separate antiprotons and positrons from the vast background of cosmic-ray electrons and protons, respectively. In this work we present the identification capabilities of the calorimeter obtained using both Monte Carlo and test beam data. We show that the calorimeter can provide a proton rejection factor of about 105 while keeping a similar to 90% efficiency in selecting electrons and positrons. The PAMELA calorimeter is therefore able to provide the identification power needed to reach the primary scientific objectives of PAMELA.
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| 24. |
- Marconi, A., et al.
(author)
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ELT-HIRES, the high resolution spectrograph for the ELT : results from the Phase A study
- 2018
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In: GROUND-BASED AND AIRBORNE INSTRUMENTATION FOR ASTRONOMY VII. - : SPIE-INT SOC OPTICAL ENGINEERING. - 9781510619586
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Conference paper (peer-reviewed)abstract
- We present the results from the phase A study of ELT-HIRES, an optical-infrared High Resolution Spectrograph for ELT, which has just been completed by a consortium of 30 institutes from 12 countries forming a team of about 200 scientists and engineers. The top science cases of ELT-HIRES will be the detection of life signatures from exoplanet atmospheres, tests on the stability of Nature's fundamental couplings, the direct detection of the cosmic acceleration. However, the science requirements of these science cases enable many other groundbreaking science cases. The baseline design, which allows to fulfil the top science cases, consists in a modular fiber fed cross-dispersed echelle spectrograph with two ultra-stable spectral arms providing a simultaneous spectral range of 0.4-1.8 pm at a spectral resolution of 100, 000. The fiber-feeding allows ELT-HIRES to have several, interchangeable observing modes including a SCAO module and a small diffraction-limited IFU.
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| 25. |
- Menden, MP, et al.
(author)
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Community assessment to advance computational prediction of cancer drug combinations in a pharmacogenomic screen
- 2019
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In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 2674-
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Journal article (peer-reviewed)abstract
- The effectiveness of most cancer targeted therapies is short-lived. Tumors often develop resistance that might be overcome with drug combinations. However, the number of possible combinations is vast, necessitating data-driven approaches to find optimal patient-specific treatments. Here we report AstraZeneca’s large drug combination dataset, consisting of 11,576 experiments from 910 combinations across 85 molecularly characterized cancer cell lines, and results of a DREAM Challenge to evaluate computational strategies for predicting synergistic drug pairs and biomarkers. 160 teams participated to provide a comprehensive methodological development and benchmarking. Winning methods incorporate prior knowledge of drug-target interactions. Synergy is predicted with an accuracy matching biological replicates for >60% of combinations. However, 20% of drug combinations are poorly predicted by all methods. Genomic rationale for synergy predictions are identified, including ADAM17 inhibitor antagonism when combined with PIK3CB/D inhibition contrasting to synergy when combined with other PI3K-pathway inhibitors in PIK3CA mutant cells.
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| 26. |
- Noske, G. D., et al.
(author)
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A Crystallographic Snapshot of SARS-CoV-2 Main Protease Maturation Process : SARS-CoV-2 Mpro maturation
- 2021
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In: Journal of Molecular Biology. - : Elsevier BV. - 0022-2836. ; 433:18
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Journal article (peer-reviewed)abstract
- SARS-CoV-2 is the causative agent of COVID-19. The dimeric form of the viral Mpro is responsible for the cleavage of the viral polyprotein in 11 sites, including its own N and C-terminus. The lack of structural information for intermediary forms of Mpro is a setback for the understanding its self-maturation process. Herein, we used X-ray crystallography combined with biochemical data to characterize multiple forms of SARS-CoV-2 Mpro. For the immature form, we show that extra N-terminal residues caused conformational changes in the positioning of domain-three over the active site, hampering the dimerization and diminishing its activity. We propose that this form preludes the cis and trans-cleavage of N-terminal residues. Using fragment screening, we probe new cavities in this form which can be used to guide therapeutic development. Furthermore, we characterized a serine site-directed mutant of the Mpro bound to its endogenous N and C-terminal residues during dimeric association stage of the maturation process. We suggest this form is a transitional state during the C-terminal trans-cleavage. This data sheds light in the structural modifications of the SARS-CoV-2 main protease during its self-maturation process.
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| 27. |
- Tinetti, G., et al.
(author)
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A chemical survey of exoplanets with ARIEL
- 2018
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In: Experimental Astronomy. - : Springer Science and Business Media LLC. - 0922-6435 .- 1572-9508. ; 46:1, s. 135-209
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Journal article (peer-reviewed)abstract
- Thousands of exoplanets have now been discovered with a huge range of masses, sizes and orbits: from rocky Earth-like planets to large gas giants grazing the surface of their host star. However, the essential nature of these exoplanets remains largely mysterious: there is no known, discernible pattern linking the presence, size, or orbital parameters of a planet to the nature of its parent star. We have little idea whether the chemistry of a planet is linked to its formation environment, or whether the type of host star drives the physics and chemistry of the planet’s birth, and evolution. ARIEL was conceived to observe a large number (~1000) of transiting planets for statistical understanding, including gas giants, Neptunes, super-Earths and Earth-size planets around a range of host star types using transit spectroscopy in the 1.25–7.8 μm spectral range and multiple narrow-band photometry in the optical. ARIEL will focus on warm and hot planets to take advantage of their well-mixed atmospheres which should show minimal condensation and sequestration of high-Z materials compared to their colder Solar System siblings. Said warm and hot atmospheres are expected to be more representative of the planetary bulk composition. Observations of these warm/hot exoplanets, and in particular of their elemental composition (especially C, O, N, S, Si), will allow the understanding of the early stages of planetary and atmospheric formation during the nebular phase and the following few million years. ARIEL will thus provide a representative picture of the chemical nature of the exoplanets and relate this directly to the type and chemical environment of the host star. ARIEL is designed as a dedicated survey mission for combined-light spectroscopy, capable of observing a large and well-defined planet sample within its 4-year mission lifetime. Transit, eclipse and phase-curve spectroscopy methods, whereby the signal from the star and planet are differentiated using knowledge of the planetary ephemerides, allow us to measure atmospheric signals from the planet at levels of 10–100 part per million (ppm) relative to the star and, given the bright nature of targets, also allows more sophisticated techniques, such as eclipse mapping, to give a deeper insight into the nature of the atmosphere. These types of observations require a stable payload and satellite platform with broad, instantaneous wavelength coverage to detect many molecular species, probe the thermal structure, identify clouds and monitor the stellar activity. The wavelength range proposed covers all the expected major atmospheric gases from e.g. H2O, CO2, CH4 NH3, HCN, H2S through to the more exotic metallic compounds, such as TiO, VO, and condensed species. Simulations of ARIEL performance in conducting exoplanet surveys have been performed – using conservative estimates of mission performance and a full model of all significant noise sources in the measurement – using a list of potential ARIEL targets that incorporates the latest available exoplanet statistics. The conclusion at the end of the Phase A study, is that ARIEL – in line with the stated mission objectives – will be able to observe about 1000 exoplanets depending on the details of the adopted survey strategy, thus confirming the feasibility of the main science objectives.
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| 28. |
- von Doetinchem, P., et al.
(author)
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Cosmic-ray antinuclei as messengers of new physics : status and outlook for the new decade
- 2020
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In: Journal of Cosmology and Astroparticle Physics. - : IOP Publishing. - 1475-7516. ; :8
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Journal article (peer-reviewed)abstract
- The precise measurement of cosmic-ray antinuclei serves as an important means for identifying the nature of dark matter and other new astrophysical phenomena, and could be used with other cosmic-ray species to understand cosmic-ray production and propagation in the Galaxy. For instance, low-energy antideuterons would provide a "smoking gun" signature of dark matter annihilation or decay, essentially free of astrophysical background. Studies in recent years have emphasized that models for cosmic-ray antideuterons must be considered together with the abundant cosmic antiprotons and any potential observation of antihelium. Therefore, a second dedicated Antideuteron Workshop was organized at UCLA in March 2019, bringing together a community of theorists and experimentalists to review the status of current observations of cosmic-ray antinuclei, the theoretical work towards understanding these signatures, and the potential of upcoming measurements to illuminate ongoing controversies. This review aims to synthesize this recent work and present implications for the upcoming decade of antinuclei observations and searches. This includes discussion of a possible dark matter signature in the AMS-02 antiproton spectrum, the most recent limits from BESS Polar-II on the cosmic antideuteron flux, and reports of candidate antihelium events by AMS-02; recent collider and cosmic-ray measurements relevant for antinuclei production models; the state of cosmic-ray transport models in light of AMS-02 and Voyager data; and the prospects for upcoming experiments, such as GAPS. This provides a roadmap for progress on cosmic antinuclei signatures of dark matter in the coming years.
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- Andres, J, et al.
(author)
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Transition-state structures for describing the enzyme-catalyzed mechanisms of rubisco
- 1999
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In: THEORETICAL CHEMISTRY ACCOUNTS. - : SPRINGER VERLAG. - 1432-881X. ; 101:1-3, s. 234-240
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Journal article (other academic/artistic)abstract
- The carboxylation and oxygenation processes of a model substrate, 3,4-dihydroxy-2-pentanone, have been theoreticaly characterized as a set of steps? mimicking the corresponding reactions of D-ribulose-1,5-bisphosphate catalyzed by rubisco. A theoretical c
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| 32. |
- Bijavara Seshashayana, Shilpa, et al.
(author)
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Stellar Population Astrophysics (SPA) with TNG
- 2024
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 683
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Journal article (peer-reviewed)abstract
- Context. The age, evolution, and chemical properties of the Galactic disk can be effectively ascertained using open clusters. Within the large program Stellar Populations Astrophysics at the Telescopio Nazionale Galileo, we specifically focused on stars in open clusters, to investigate various astrophysical topics, from the chemical content of very young systems to the abundance patterns of lesser studied intermediate-age and old open clusters.Aims. We investigate the astrophysically interesting element fluorine (F), which has an uncertain and intriguing cosmic origin. We also determine the abundance of cerium (Ce), as F abundance is expected to correlate with the s-process elements. We intend to determine the trend of F abundance across the Galactic disk as a function of metallicity and age. This will offer insights into Galactic chemical evolution models, potentially enhancing our comprehension of this element’s cosmic origin.Methods. High-resolution near-infrared spectra were obtained using the GIANO-B spectrograph. The Python version of Spectroscopy Made Easy (PySME), was used to derive atmospheric parameters and abundances. The stellar parameters were determined using OH, CN, and CO molecular lines along with Fe I lines. The F and Ce abundances were inferred using two K-band HF lines (λλ 2.28, 2.33 µm) and two atomic H-band lines (λλ 1.66, and 1.71 µm), respectively.Results. Of all the clusters in our sample, only King 11 had not been previously studied through medium- to high-resolution spectroscopy, and our stellar parameter and metallicity findings align well with those documented in the literature. We have successfully inferred F and Ce abundances in all seven open clusters and probed the radial and age distributions of abundance ratios. This paper presents the first F Galactic radial abundance gradient. Our results are also compared with literature estimates and with Galactic chemical evolution models that have been generated using different F production channels.Conclusions. Our results indicate a constant, solar pattern in the [F/Fe] ratios across clusters of different ages, supporting the latest findings that fluorine levels do not exhibit any secondary behavior for stars with solar or above-solar metallicity. However, an exception to this trend is seen in NGC 6791, a metal-rich, ancient cluster whose chemical composition is distinct due to its enhanced fluorine abundance. This anomaly strengthens the hypothesis that NGC 6791 originated in the inner regions of the Galaxy before migrating to its present position. By comparing our sample stars with the predictions of Galactic chemical evolution models, we came to the conclusion that both asymptotic giant branch stars and massive stars, including a fraction of fast rotators that increase with decreasing metallicity, are needed to explain the cosmic origin of F.
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| 35. |
- Cirasuolo, M., et al.
(author)
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MOONS: the Multi-Object Optical and Near-infrared Spectrograph for the VLT
- 2014
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In: Ground-based and Airborne Instrumentation for Astronomy V. - : SPIE. - 0277-786X .- 1996-756X. ; 9147, s. 91470-91470
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Conference paper (peer-reviewed)abstract
- MOONS (the Multi-Object Optical and Near-infrared Spectrograph) has been selected by ESO as a third-generation instrument for the Very Large Telescope (VLT). The light grasp of the large collecting area offered by the VLT (8.2m diameter), combined with the large multiplex and wavelength coverage (optical to near-IR: 0.8 -1.8 mu m) of MOONS will provide the European astronomical community with a powerful, unique instrument able to pioneer a wide range of Galactic, extragalactic and cosmological studies, and it will provide crucial follow-up for major facilities such as Gaia, VISTA, Euclid and LSST. MOONS has the observational power needed to unveil galaxy formation and evolution over the entire history of the Universe, from stars in our Milky Way, through the redshift desert, and up to the epoch of very first galaxies and reionization of the Universe at redshifts of z > 8-9, just a few million years after the Big Bang. From five years of observations MOONS will provide high-quality spectra for > 3M stars in our Galaxy and the Local Group, and for 1-2M galaxies at z > 1 (for an SDSS-like survey), promising to revolutionize our understanding of the Universe. The baseline design consists of similar to 1000 fibres, deployable over a field-of-view of similar to 500 arcmin(2), the largest patrol field offered by the Nasmyth focus at the VLT. The total wavelength coverage is 0.8 -1.8 mu m with two spectral resolving powers: in the medium-resolution mode (R similar to 4,000-6,000) the entire wavelength range is observed simultaneously, while the high-resolution mode will cover three selected sub-regions simultaneously: one region with R similar to 8,000 near the Ca II triplet to measure stellar radial velocities, and two regions at R similar to 20,000 (one in each of the J- and H-bands), for precision measurements of chemical abundances.
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| 40. |
- Dorn, R. J., et al.
(author)
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CRIRES+ on sky at the ESO Very Large Telescope : Observing the Universe at infrared wavelengths and high spectral resolution
- 2023
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 671
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Journal article (peer-reviewed)abstract
- The CRyogenic InfraRed Echelle Spectrograph (CRIRES) Upgrade project CRIRES+ extended the capabilities of CRIRES. It transformed this VLT instrument into a cross-dispersed spectrograph to increase the wavelength range that is covered simultaneously by up to a factor of ten. In addition, a new detector focal plane array of three Hawaii 2RG detectors with a 5.3 mu m cutoff wavelength replaced the existing detectors. Amongst many other improvements, a new spectropolarimetric unit was added and the calibration system has been enhanced. The instrument was installed at the VLT on Unit Telescope 3 at the beginning of 2020 and successfully commissioned and verified for science operations during 2021, partly remotely from Europe due to the COVID-19 pandemic. The instrument was subsequently offered to the community from October 2021 onwards. This article describes the performance and capabilities of the upgraded instrument and presents on sky results.
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| 46. |
- Lensink, Marc F., et al.
(author)
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Impact of AlphaFold on structure prediction of protein complexes: The CASP15-CAPRI experiment
- 2023
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In: Proteins. - : WILEY. - 0887-3585 .- 1097-0134.
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Journal article (peer-reviewed)abstract
- We present the results for CAPRI Round 54, the 5th joint CASP-CAPRI protein assembly prediction challenge. The Round offered 37 targets, including 14 homodimers, 3 homo-trimers, 13 heterodimers including 3 antibody-antigen complexes, and 7 large assemblies. On average similar to 70 CASP and CAPRI predictor groups, including more than 20 automatics servers, submitted models for each target. A total of 21 941 models submitted by these groups and by 15 CAPRI scorer groups were evaluated using the CAPRI model quality measures and the DockQ score consolidating these measures. The prediction performance was quantified by a weighted score based on the number of models of acceptable quality or higher submitted by each group among their five best models. Results show substantial progress achieved across a significant fraction of the 60+ participating groups. High-quality models were produced for about 40% of the targets compared to 8% two years earlier. This remarkable improvement is due to the wide use of the AlphaFold2 and AlphaFold2-Multimer software and the confidence metrics they provide. Notably, expanded sampling of candidate solutions by manipulating these deep learning inference engines, enriching multiple sequence alignments, or integration of advanced modeling tools, enabled top performing groups to exceed the performance of a standard AlphaFold2-Multimer version used as a yard stick. This notwithstanding, performance remained poor for complexes with antibodies and nanobodies, where evolutionary relationships between the binding partners are lacking, and for complexes featuring conformational flexibility, clearly indicating that the prediction of protein complexes remains a challenging problem.
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| 47. |
- Lindh, Markus V., et al.
(author)
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Consequences of increased temperature and acidification on bacterioplankton community composition during a mesocosm spring bloom in the Baltic Sea
- 2013
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In: Environmental Microbiology Reports. - : Wiley. - 1758-2229. ; 5:2, s. 252-262
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Journal article (peer-reviewed)abstract
- Despite the paramount importance of bacteria for biogeochemical cycling of carbon and nutrients, little is known about the potential effects of climate change on these key organisms. The consequences of the projected climate change on bacterioplankton community dynamics were investigated in a Baltic Sea spring phytoplankton bloom mesocosm experiment by increasing temperature with 3°C and decreasing pH by approximately 0.4 units via CO2 addition in a factorial design. Temperature was the major driver of differences in community composition during the experiment, as shown by denaturing gradient gel electrophoresis (DGGE) of amplified 16S rRNA gene fragments. Several bacterial phylotypes belonging to Betaproteobacteria were predominant at 3°C but were replaced by members of the Bacteriodetes in the 6°C mesocosms. Acidification alone had a limited impact on phylogenetic composition, but when combined with increased temperature, resulted in the proliferation of specific microbial phylotypes. Our results suggest that although temperature is an important driver in structuring bacterioplankton composition, evaluation of the combined effects of temperature and acidification is necessary to fully understand consequences of climate change for marine bacterioplankton, their implications for future spring bloom dynamics, and their role in ecosystem functioning.
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