| 1. |
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| 2. |
- Glasbey, JC, et al.
(author)
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- 2021
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swepub:Mat__t
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| 3. |
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| 4. |
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| 5. |
- Tabiri, S, et al.
(author)
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- 2021
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swepub:Mat__t
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| 6. |
- Bravo, L, et al.
(author)
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- 2021
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swepub:Mat__t
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| 7. |
- Niemi, MEK, et al.
(author)
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- 2021
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swepub:Mat__t
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| 8. |
- Kanai, M, et al.
(author)
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- 2023
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swepub:Mat__t
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| 9. |
- Aamodt, K., et al.
(author)
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First proton-proton collisions at the LHC as observed with the ALICE detector: measurement of the charged-particle pseudorapidity density at root s=900 GeV
- 2010
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In: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044. ; 65:1-2, s. 111-125
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Journal article (peer-reviewed)abstract
- On 23rd November 2009, during the early commissioning of the CERN Large Hadron Collider (LHC), two counter-rotating proton bunches were circulated for the first time concurrently in the machine, at the LHC injection energy of 450 GeV per beam. Although the proton intensity was very low, with only one pilot bunch per beam, and no systematic attempt was made to optimize the collision optics, all LHC experiments reported a number of collision candidates. In the ALICE experiment, the collision region was centred very well in both the longitudinal and transverse directions and 284 events were recorded in coincidence with the two passing proton bunches. The events were immediately reconstructed and analyzed both online and offline. We have used these events to measure the pseudorapidity density of charged primary particles in the central region. In the range vertical bar eta vertical bar < 0.5, we obtain dN(ch)/d eta = 3.10 +/- 0.13(stat.) +/- 0.22(syst.) for all inelastic interactions, and dN(ch)/d eta = 3.51 +/- 0.15(stat.) +/- 0.25(syst.) for nonsingle diffractive interactions. These results are consistent with previous measurements in proton-antiproton interactions at the same centre-of-mass energy at the CERN Sp<(p)over bar>S collider. They also illustrate the excellent functioning and rapid progress of the LHC accelerator, and of both the hardware and software of the ALICE experiment, in this early start-up phase.
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| 10. |
- Aamodt, K., et al.
(author)
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Alignment of the ALICE Inner Tracking System with cosmic-ray tracks
- 2010
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In: Journal of Instrumentation. - 1748-0221. ; 5
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Conference paper (peer-reviewed)abstract
- ALICE (A Large Ion Collider Experiment) is the LHC (Large Hadron Collider) experiment devoted to investigating the strongly interacting matter created in nucleus-nucleus collisions at the LHC energies. The ALICE ITS, Inner Tracking System, consists of six cylindrical layers of silicon detectors with three different technologies; in the outward direction: two layers of pixel detectors, two layers each of drift, and strip detectors. The number of parameters to be determined in the spatial alignment of the 2198 sensor modules of the ITS is about 13,000. The target alignment precision is well below 10 mu m in some cases (pixels). The sources of alignment information include survey measurements, and the reconstructed tracks from cosmic rays and from proton-proton collisions. The main track-based alignment method uses the Millepede global approach. An iterative local method was developed and used as well. We present the results obtained for the ITS alignment using about 10(5) charged tracks from cosmic rays that have been collected during summer 2008, with the ALICE solenoidal magnet switched off.
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| 11. |
- Aamodt, K., et al.
(author)
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Charged-particle multiplicity measurement in proton-proton collisions at root s=0.9 and 2.36 TeV with ALICE at LHC
- 2010
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In: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044. ; 68:1-2, s. 89-108
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Journal article (peer-reviewed)abstract
- Charged-particle production was studied in proton-proton collisions collected at the LHC with the ALICE detector at centre-of-mass energies 0.9 TeV and 2.36 TeV in the pseudorapidity range vertical bar eta vertical bar < 1.4. In the central region (vertical bar eta vertical bar < 0.5), at 0.9 TeV, we measure charged-particle pseudo-rapidity density dN(ch)/d eta = 3.02 +/- 0.01(stat.)(-0.05)(+0.08)(syst.) for inelastic interactions, and dN(ch)/d eta = 3.58 +/- 0.01 (stat.)(-0.12)(+0.12)(syst.) for non-single-diffractive interactions. At 2.36 TeV, we find dN(ch)/d eta = 3.77 +/- 0.01(stat.)(-0.12)(+0.25)(syst.) for inelastic, and dN(ch)/d eta = 4.43 +/- 0.01(stat.)(-0.12)(+0.17)(syst.) for non-single-diffractive collisions. The relative increase in charged-particle multiplicity from the lower to higher energy is 24.7% +/- 0.5%(stat.)(-2.8)(+5.7)%(syst.) for inelastic and 23.7% +/- 0.5%(stat.)(-1.1)(+4.6)%(syst.) for non-single-diffractive interactions. This increase is consistent with that reported by the CMS collaboration for non-single-diffractive events and larger than that found by a number of commonly used models. The multiplicity distribution was measured in different pseudorapidity intervals and studied in terms of KNO variables at both energies. The results are compared to proton-antiproton data and to model predictions.
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| 12. |
- Aamodt, K., et al.
(author)
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Charged-particle multiplicity measurement in proton-proton collisions at root s=7 TeV with ALICE at LHC
- 2010
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In: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044. ; 68:3-4, s. 345-354
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Journal article (peer-reviewed)abstract
- The pseudorapidity density and multiplicity distribution of charged particles produced in proton-proton collisions at the LHC, at a centre-of-mass energy root s = 7 TeV, were measured in the central pseudorapidity region vertical bar eta vertical bar < 1. Comparisons are made with previous measurements at root s = 0.9 TeV and 2.36 TeV. At root s = 7 TeV, for events with at least one charged particle in |eta vertical bar| < 1, we obtain dN(ch)/d eta = 6.01 +/- 0.01(stat.)(-0.12)(+0.20) (syst.). This corresponds to an increase of 57.6%+/-0.4%(stat.)(-1.8%)(+3.6) (syst.) relative to collisions at 0.9 TeV, significantly higher than calculations from commonly used models. The multiplicity distribution at 7 TeV is described fairly well by the negative binomial distribution.
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| 13. |
- Aamodt, K., et al.
(author)
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Midrapidity Antiproton-to-Proton Ratio in pp Collisons root s=0.9 and 7 TeV Measured by the ALICE Experiment
- 2010
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In: Physical Review Letters. - 1079-7114. ; 105:7
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Journal article (peer-reviewed)abstract
- The ratio of the yields of antiprotons to protons in pp collisions has been measured by the ALICE experiment at root s = 0.9 and 7 TeV during the initial running periods of the Large Hadron Collider. The measurement covers the transverse momentum interval 0.45 < p(t) < 1.05 GeV/c and rapidity vertical bar y vertical bar < 0.5. The ratio is measured to be R-vertical bar y vertical bar<0.5 = 0.957 +/- 0.006(stat) +/- 0.0014(syst) at 0.9 Tev and R-vertical bar y vertical bar<0.5 = 0.991 +/- 0.005 +/- 0.014(syst) at 7 TeV and it is independent of both rapidity and transverse momentum. The results are consistent with the conventional model of baryon-number transport and set stringent limits on any additional contributions to baryon-number transfer over very large rapidity intervals in pp collisions.
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| 14. |
- Aamodt, K., et al.
(author)
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Two-pion Bose-Einstein correlations in pp collisions at root s=900 GeV
- 2010
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In: Physical Review D (Particles, Fields, Gravitation and Cosmology). - 1550-2368. ; 82:5
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Journal article (peer-reviewed)abstract
- We report on the measurement of two-pion correlation functions from pp collisions at root s = 900 GeV performed by the ALICE experiment at the Large Hadron Collider. Our analysis shows an increase of the Hanbury Brown-Twiss radius with increasing event multiplicity, in line with other measurements done in particle- and nuclear collisions. Conversely, the strong decrease of the radius with increasing transverse momentum, as observed at the Relativistic Heavy Ion Collider and at Tevatron, is not manifest in our data.
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| 15. |
- Aamodt, K., et al.
(author)
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Production of pions, kaons and protons in pp collisions at root s=900 GeV with ALICE at the LHC
- 2011
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In: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044. ; 71:6
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Journal article (peer-reviewed)abstract
- The production of pi(+), pi(-), K+, K-, p, and (p) over bar at mid-rapidity has been measured in proton-proton collisions at root s = 900 GeV with the ALICE detector. Particle identification is performed using the specific energy loss in the inner tracking silicon detector and the time projection chamber. In addition, time-of-flight information is used to identify hadrons at higher momenta. Finally, the distinctive kink topology of the weak decay of charged kaons is used for an alternative measurement of the kaon transverse momentum (p(t)) spectra. Since these various particle identification tools give the best separation capabilities over different momentum ranges, the results are combined to extract spectra from p(t) = 100 MeV/c to 2.5 GeV/c. The measured spectra are further compared with QCD-inspired models which yield a poor description. The total yields and the mean pt are compared with previous measurements, and the trends as a function of collision energy are discussed.
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| 16. |
- Aamodt, K., et al.
(author)
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Transverse momentum spectra of charged particles in proton-proton collisions at root s=900 GeV with ALICE at the LHC
- 2010
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In: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 693:2, s. 53-68
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Journal article (peer-reviewed)abstract
- The inclusive charged particle transverse momentum distribution is measured in proton-proton collisions at root s = 900 GeV at the LHC using the ALICE detector. The measurement is performed in the central pseudorapidity region (vertical bar eta vertical bar < 0.8) over the transverse momentum range 0.15 < p(T) < 10 GeV/c. The correlation between transverse momentum and particle multiplicity is also studied. Results are presented for inelastic (INEL) and non-single-diffractive (NSD) events. The average transverse momentum for vertical bar eta vertical bar < 0.8 is < p(T)>(INEL) = 0.483 +/- 0.001 (stat.) +/- 0.007 (syst.) GeV/c and < p(T)>(NSD) = 0.489 +/- 0.001 (stat.) +/- 0.007 (syst.) GeV/c, respectively. The data exhibit a slightly larger < p(T)> than measurements in wider pseudorapidity intervals. The results are compared to simulations with the Monte Carlo event generators PYTHIA and PHOJET. (C) 2010 Published by Elsevier B.V.
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| 17. |
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| 18. |
- Abel, I, et al.
(author)
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Overview of the JET results with the ITER-like wall
- 2013
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In: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 53:10, s. 104002-
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Journal article (peer-reviewed)abstract
- Following the completion in May 2011 of the shutdown for the installation of the beryllium wall and the tungsten divertor, the first set of JET campaigns have addressed the investigation of the retention properties and the development of operational scenarios with the new plasma-facing materials. The large reduction in the carbon content (more than a factor ten) led to a much lower Z(eff) (1.2-1.4) during L- and H-mode plasmas, and radiation during the burn-through phase of the plasma initiation with the consequence that breakdown failures are almost absent. Gas balance experiments have shown that the fuel retention rate with the new wall is substantially reduced with respect to the C wall. The re-establishment of the baseline H-mode and hybrid scenarios compatible with the new wall has required an optimization of the control of metallic impurity sources and heat loads. Stable type-I ELMy H-mode regimes with H-98,H-y2 close to 1 and beta(N) similar to 1.6 have been achieved using gas injection. ELM frequency is a key factor for the control of the metallic impurity accumulation. Pedestal temperatures tend to be lower with the new wall, leading to reduced confinement, but nitrogen seeding restores high pedestal temperatures and confinement. Compared with the carbon wall, major disruptions with the new wall show a lower radiated power and a slower current quench. The higher heat loads on Be wall plasma-facing components due to lower radiation made the routine use of massive gas injection for disruption mitigation essential.
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| 19. |
- Romanelli, F, et al.
(author)
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Overview of the JET results
- 2011
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In: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 51:9
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Journal article (peer-reviewed)abstract
- Since the last IAEA Conference JET has been in operation for one year with a programmatic focus on the qualification of ITER operating scenarios, the consolidation of ITER design choices and preparation for plasma operation with the ITER-like wall presently being installed in JET. Good progress has been achieved, including stationary ELMy H-mode operation at 4.5 MA. The high confinement hybrid scenario has been extended to high triangularity, lower ρ*and to pulse lengths comparable to the resistive time. The steady-state scenario has also been extended to lower ρ*and ν*and optimized to simultaneously achieve, under stationary conditions, ITER-like values of all other relevant normalized parameters. A dedicated helium campaign has allowed key aspects of plasma control and H-mode operation for the ITER non-activated phase to be evaluated. Effective sawtooth control by fast ions has been demonstrated with3He minority ICRH, a scenario with negligible minority current drive. Edge localized mode (ELM) control studies using external n = 1 and n = 2 perturbation fields have found a resonance effect in ELM frequency for specific q95values. Complete ELM suppression has, however, not been observed, even with an edge Chirikov parameter larger than 1. Pellet ELM pacing has been demonstrated and the minimum pellet size needed to trigger an ELM has been estimated. For both natural and mitigated ELMs a broadening of the divertor ELM-wetted area with increasing ELM size has been found. In disruption studies with massive gas injection up to 50% of the thermal energy could be radiated before, and 20% during, the thermal quench. Halo currents could be reduced by 60% and, using argon/deuterium and neon/deuterium gas mixtures, runaway electron generation could be avoided. Most objectives of the ITER-like ICRH antenna have been demonstrated; matching with closely packed straps, ELM resilience, scattering matrix arc detection and operation at high power density (6.2 MW m-2) and antenna strap voltages (42 kV). Coupling measurements are in very good agreement with TOPICA modelling. © 2011 IAEA, Vienna.
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| 20. |
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| 21. |
- Lozano, Rafael, et al.
(author)
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Measuring progress from 1990 to 2017 and projecting attainment to 2030 of the health-related Sustainable Development Goals for 195 countries and territories: a systematic analysis for the Global Burden of Disease Study 2017
- 2018
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In: The Lancet. - : Elsevier. - 1474-547X .- 0140-6736. ; 392:10159, s. 2091-2138
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Journal article (peer-reviewed)abstract
- Background: Efforts to establish the 2015 baseline and monitor early implementation of the UN Sustainable Development Goals (SDGs) highlight both great potential for and threats to improving health by 2030. To fully deliver on the SDG aim of “leaving no one behind”, it is increasingly important to examine the health-related SDGs beyond national-level estimates. As part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD 2017), we measured progress on 41 of 52 health-related SDG indicators and estimated the health-related SDG index for 195 countries and territories for the period 1990–2017, projected indicators to 2030, and analysed global attainment. Methods: We measured progress on 41 health-related SDG indicators from 1990 to 2017, an increase of four indicators since GBD 2016 (new indicators were health worker density, sexual violence by non-intimate partners, population census status, and prevalence of physical and sexual violence [reported separately]). We also improved the measurement of several previously reported indicators. We constructed national-level estimates and, for a subset of health-related SDGs, examined indicator-level differences by sex and Socio-demographic Index (SDI) quintile. We also did subnational assessments of performance for selected countries. To construct the health-related SDG index, we transformed the value for each indicator on a scale of 0–100, with 0 as the 2·5th percentile and 100 as the 97·5th percentile of 1000 draws calculated from 1990 to 2030, and took the geometric mean of the scaled indicators by target. To generate projections through 2030, we used a forecasting framework that drew estimates from the broader GBD study and used weighted averages of indicator-specific and country-specific annualised rates of change from 1990 to 2017 to inform future estimates. We assessed attainment of indicators with defined targets in two ways: first, using mean values projected for 2030, and then using the probability of attainment in 2030 calculated from 1000 draws. We also did a global attainment analysis of the feasibility of attaining SDG targets on the basis of past trends. Using 2015 global averages of indicators with defined SDG targets, we calculated the global annualised rates of change required from 2015 to 2030 to meet these targets, and then identified in what percentiles the required global annualised rates of change fell in the distribution of country-level rates of change from 1990 to 2015. We took the mean of these global percentile values across indicators and applied the past rate of change at this mean global percentile to all health-related SDG indicators, irrespective of target definition, to estimate the equivalent 2030 global average value and percentage change from 2015 to 2030 for each indicator. Findings: The global median health-related SDG index in 2017 was 59·4 (IQR 35·4–67·3), ranging from a low of 11·6 (95% uncertainty interval 9·6–14·0) to a high of 84·9 (83·1–86·7). SDG index values in countries assessed at the subnational level varied substantially, particularly in China and India, although scores in Japan and the UK were more homogeneous. Indicators also varied by SDI quintile and sex, with males having worse outcomes than females for non-communicable disease (NCD) mortality, alcohol use, and smoking, among others. Most countries were projected to have a higher health-related SDG index in 2030 than in 2017, while country-level probabilities of attainment by 2030 varied widely by indicator. Under-5 mortality, neonatal mortality, maternal mortality ratio, and malaria indicators had the most countries with at least 95% probability of target attainment. Other indicators, including NCD mortality and suicide mortality, had no countries projected to meet corresponding SDG targets on the basis of projected mean values for 2030 but showed some probability of attainment by 2030. For some indicators, including child malnutrition, several infectious diseases, and most violence measures, the annualised rates of change required to meet SDG targets far exceeded the pace of progress achieved by any country in the recent past. We found that applying the mean global annualised rate of change to indicators without defined targets would equate to about 19% and 22% reductions in global smoking and alcohol consumption, respectively; a 47% decline in adolescent birth rates; and a more than 85% increase in health worker density per 1000 population by 2030. Interpretation: The GBD study offers a unique, robust platform for monitoring the health-related SDGs across demographic and geographic dimensions. Our findings underscore the importance of increased collection and analysis of disaggregated data and highlight where more deliberate design or targeting of interventions could accelerate progress in attaining the SDGs. Current projections show that many health-related SDG indicators, NCDs, NCD-related risks, and violence-related indicators will require a concerted shift away from what might have driven past gains—curative interventions in the case of NCDs—towards multisectoral, prevention-oriented policy action and investments to achieve SDG aims. Notably, several targets, if they are to be met by 2030, demand a pace of progress that no country has achieved in the recent past. The future is fundamentally uncertain, and no model can fully predict what breakthroughs or events might alter the course of the SDGs. What is clear is that our actions—or inaction—today will ultimately dictate how close the world, collectively, can get to leaving no one behind by 2030.
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| 22. |
- Stanaway, Jeffrey D., et al.
(author)
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Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks for 195 countries and territories, 1990-2017: A systematic analysis for the Global Burden of Disease Study 2017
- 2018
-
In: The Lancet. - 1474-547X .- 0140-6736. ; 392:10159, s. 1923-1994
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Journal article (peer-reviewed)abstract
- Background The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 comparative risk assessment (CRA) is a comprehensive approach to risk factor quantification that offers a useful tool for synthesising evidence on risks and risk-outcome associations. With each annual GBD study, we update the GBD CRA to incorporate improved methods, new risks and risk-outcome pairs, and new data on risk exposure levels and risk- outcome associations. Methods We used the CRA framework developed for previous iterations of GBD to estimate levels and trends in exposure, attributable deaths, and attributable disability-adjusted life-years (DALYs), by age group, sex, year, and location for 84 behavioural, environmental and occupational, and metabolic risks or groups of risks from 1990 to 2017. This study included 476 risk-outcome pairs that met the GBD study criteria for convincing or probable evidence of causation. We extracted relative risk and exposure estimates from 46 749 randomised controlled trials, cohort studies, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. Using the counterfactual scenario of theoretical minimum risk exposure level (TMREL), we estimated the portion of deaths and DALYs that could be attributed to a given risk. We explored the relationship between development and risk exposure by modelling the relationship between the Socio-demographic Index (SDI) and risk-weighted exposure prevalence and estimated expected levels of exposure and risk-attributable burden by SDI. Finally, we explored temporal changes in risk-attributable DALYs by decomposing those changes into six main component drivers of change as follows: (1) population growth; (2) changes in population age structures; (3) changes in exposure to environmental and occupational risks; (4) changes in exposure to behavioural risks; (5) changes in exposure to metabolic risks; and (6) changes due to all other factors, approximated as the risk-deleted death and DALY rates, where the risk-deleted rate is the rate that would be observed had we reduced the exposure levels to the TMREL for all risk factors included in GBD 2017.
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| 23. |
- Meyer, H., et al.
(author)
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Overview of physics results from MAST towards ITER/DEMO and the MAST Upgrade
- 2013
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In: Nuclear Fusion. - : IOP Publishing. - 0029-5515 .- 1741-4326. ; 53:10, s. 104008-
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Journal article (peer-reviewed)abstract
- New diagnostic, modelling and plant capability on the Mega Ampere Spherical Tokamak (MAST) have delivered important results in key areas for ITER/DEMO and the upcoming MAST Upgrade, a step towards future ST devices on the path to fusion currently under procurement. Micro-stability analysis of the pedestal highlights the potential roles of micro-tearing modes and kinetic ballooning modes for the pedestal formation. Mitigation of edge localized modes (ELM) using resonant magnetic perturbation has been demonstrated for toroidal mode numbers n = 3, 4, 6 with an ELM frequency increase by up to a factor of 9, compatible with pellet fuelling. The peak heat flux of mitigated and natural ELMs follows the same linear trend with ELM energy loss and the first ELM-resolved T-i measurements in the divertor region are shown. Measurements of flow shear and turbulence dynamics during L-H transitions show filaments erupting from the plasma edge whilst the full flow shear is still present. Off-axis neutral beam injection helps to strongly reduce the redistribution of fast-ions due to fishbone modes when compared to on-axis injection. Low-k ion-scale turbulence has been measured in L-mode and compared to global gyro-kinetic simulations. A statistical analysis of principal turbulence time scales shows them to be of comparable magnitude and reasonably correlated with turbulence decorrelation time. T-e inside the island of a neoclassical tearing mode allow the analysis of the island evolution without assuming specific models for the heat flux. Other results include the discrepancy of the current profile evolution during the current ramp-up with solutions of the poloidal field diffusion equation, studies of the anomalous Doppler resonance compressional Alfven eigenmodes, disruption mitigation studies and modelling of the new divertor design for MAST Upgrade. The novel 3D electron Bernstein synthetic imaging shows promising first data sensitive to the edge current profile and flows.
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| 24. |
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| 25. |
- Serge, M. A., et al.
(author)
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Testing the Effect of Relative Pollen Productivity on the REVEALS Model : A Validated Reconstruction of Europe-Wide Holocene Vegetation
- 2023
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In: Land. - : MDPI. - 2073-445X. ; 12:5
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Journal article (peer-reviewed)abstract
- Reliable quantitative vegetation reconstructions for Europe during the Holocene are crucial to improving our understanding of landscape dynamics, making it possible to assess the past effects of environmental variables and land-use change on ecosystems and biodiversity, and mitigating their effects in the future. We present here the most spatially extensive and temporally continuous pollen-based reconstructions of plant cover in Europe (at a spatial resolution of 1 degrees x 1 degrees) over the Holocene (last 11.7 ka BP) using the 'Regional Estimates of VEgetation Abundance from Large Sites' (REVEALS) model. This study has three main aims. First, to present the most accurate and reliable generation of REVEALS reconstructions across Europe so far. This has been achieved by including a larger number of pollen records compared to former analyses, in particular from the Mediterranean area. Second, to discuss methodological issues in the quantification of past land cover by using alternative datasets of relative pollen productivities (RPPs), one of the key input parameters of REVEALS, to test model sensitivity. Finally, to validate our reconstructions with the global forest change dataset. The results suggest that the RPPs.st1 (31 taxa) dataset is best suited to producing regional vegetation cover estimates for Europe. These reconstructions offer a long-term perspective providing unique possibilities to explore spatial-temporal changes in past land cover and biodiversity.
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| 26. |
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| 27. |
- Matuozzo, D, et al.
(author)
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Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19
- 2022
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In: medRxiv : the preprint server for health sciences. - : Cold Spring Harbor Laboratory.
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Journal article (other academic/artistic)abstract
- BackgroundWe previously reported inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity in 1-5% of unvaccinated patients with life-threatening COVID-19, and auto-antibodies against type I IFN in another 15-20% of cases.MethodsWe report here a genome-wide rare variant burden association analysis in 3,269 unvaccinated patients with life-threatening COVID-19 (1,301 previously reported and 1,968 new patients), and 1,373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. A quarter of the patients tested had antibodies against type I IFN (234 of 928) and were excluded from the analysis.ResultsNo gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants wasTLR7, with an OR of 27.68 (95%CI:1.5-528.7,P=1.1×10−4), in analyses restricted to biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR=3.70 [95%CI:1.3-8.2],P=2.1×10−4). Adding the recently reportedTYK2COVID-19 locus strengthened this enrichment, particularly under a recessive model (OR=19.65 [95%CI:2.1-2635.4];P=3.4×10−3). When these 14 loci andTLR7were considered, all individuals hemizygous (n=20) or homozygous (n=5) for pLOF or bLOF variants were patients (OR=39.19 [95%CI:5.2-5037.0],P=4.7×10−7), who also showed an enrichment in heterozygous variants (OR=2.36 [95%CI:1.0-5.9],P=0.02). Finally, the patients with pLOF or bLOF variants at these 15 loci were significantly younger (mean age [SD]=43.3 [20.3] years) than the other patients (56.0 [17.3] years;P=1.68×10−5).ConclusionsRare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old.
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| 28. |
- Birney, Ewan, et al.
(author)
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Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project
- 2007
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 447:7146, s. 799-816
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Journal article (peer-reviewed)abstract
- We report the generation and analysis of functional data from multiple, diverse experiments performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project. These data have been further integrated and augmented by a number of evolutionary and computational analyses. Together, our results advance the collective knowledge about human genome function in several major areas. First, our studies provide convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts, including non-protein-coding transcripts, and those that extensively overlap one another. Second, systematic examination of transcriptional regulation has yielded new understanding about transcription start sites, including their relationship to specific regulatory sequences and features of chromatin accessibility and histone modification. Third, a more sophisticated view of chromatin structure has emerged, including its inter-relationship with DNA replication and transcriptional regulation. Finally, integration of these new sources of information, in particular with respect to mammalian evolution based on inter- and intra-species sequence comparisons, has yielded new mechanistic and evolutionary insights concerning the functional landscape of the human genome. Together, these studies are defining a path for pursuit of a more comprehensive characterization of human genome function.
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| 31. |
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| 32. |
- Mahajan, Anubha, et al.
(author)
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Multi-ancestry genetic study of type 2 diabetes highlights the power of diverse populations for discovery and translation
- 2022
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In: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 54:5, s. 560-572
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Journal article (peer-reviewed)abstract
- We assembled an ancestrally diverse collection of genome-wide association studies (GWAS) of type 2 diabetes (T2D) in 180,834 affected individuals and 1,159,055 controls (48.9% non-European descent) through the Diabetes Meta-Analysis of Trans-Ethnic association studies (DIAMANTE) Consortium. Multi-ancestry GWAS meta-analysis identified 237 loci attaining stringent genome-wide significance (P < 5 x 10(-9)), which were delineated to 338 distinct association signals. Fine-mapping of these signals was enhanced by the increased sample size and expanded population diversity of the multi-ancestry meta-analysis, which localized 54.4% of T2D associations to a single variant with >50% posterior probability. This improved fine-mapping enabled systematic assessment of candidate causal genes and molecular mechanisms through which T2D associations are mediated, laying the foundations for functional investigations. Multi-ancestry genetic risk scores enhanced transferability of T2D prediction across diverse populations. Our study provides a step toward more effective clinical translation of T2D GWAS to improve global health for all, irrespective of genetic background. Genome-wide association and fine-mapping analyses in ancestrally diverse populations implicate candidate causal genes and mechanisms underlying type 2 diabetes. Trans-ancestry genetic risk scores enhance transferability across populations.
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| 33. |
- Allen, G., et al.
(author)
-
South East Pacific atmospheric composition and variability sampled = ong 20 degrees S during VOCALS-REx
- 2011
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In: Atmospheric Chemistry And Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 11:11, s. 5237-5262
-
Journal article (peer-reviewed)abstract
- The VAMOS Ocean-Cloud-Atmosphere-Land Regional Experiment (VOCALS-REx) was conducted from 15 October to 15 November 2008 in the South East Pacific (SEP) region to investigate interactions between land, sea and atmosphere in this unique tropical eastern ocean environment and to improve the skill of global and regional models in = presenting the region. This study synthesises selected aircraft, ship = d surface site observations from VOCALS-REx to statistically summarise = d characterise the atmospheric composition and variability of the = rine Boundary Layer (MBL) and Free Troposphere (FT) along the 20 = grees S parallel between 70 degrees W and 85 degrees W. Significant = nal gradients in mean MBL sub-micron aerosol particle size and = mposition, carbon monoxide, sulphur dioxide and ozone were seen over = e campaign, with a generally more variable and polluted coastal = vironment and a less variable, more pristine remote maritime regime. = adients in aerosol and trace gas concentrations were observed to be = sociated with strong gradients in cloud droplet number. The FT was = ten more polluted in terms of trace gases than the MBL in the mean; = wever increased variability in the FT composition suggests an episodic = ture to elevated concentrations. This is consistent with a complex = rtical interleaving of airmasses with diverse sources and hence = llutant concentrations as seen by generalised back trajectory = alysis, which suggests contributions from both local and long-range = urces. Furthermore, back trajectory analysis demonstrates that the = served zonal gradients both in the boundary layer and the free = oposphere are characteristic of marked changes in airmass history with = stance offshore - coastal boundary layer airmasses having been in = cent contact with the local land surface and remote maritime airmasses = ving resided over ocean for in excess of ten days. Boundary layer = mposition to the east of 75 degrees W was observed to be dominated by = astal emissions from sources to the west of the Andes, with evidence = r diurnal pumping of the Andean boundary layer above the height of the = rine capping inversion. Analysis of intra-campaign variability in = mospheric composition was not found to be significantly correlated = th observed low-frequency variability in the large scale flow pattern; = mpaign-average interquartile ranges of CO, SO(2) and O(3) = ncentrations at all longitudes were observed to dominate over much = aller differences in median concentrations calculated between periods = different flow regimes. The campaign climatology presented here aims = provide a valuable dataset to inform model simulation and future = ocess studies, particularly in the context of aerosol-cloud = teraction and further evaluation of dynamical processes in the SEP = gion for conditions analogous to those during VOCALS-REx. To this end, = r results are discussed in terms of coastal, transitional and remote = atial regimes in the MBL and FT and a gridded dataset are provided as = resource.
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| 34. |
- Campbell, TM, et al.
(author)
-
Respiratory viral infections in otherwise healthy humans with inherited IRF7 deficiency
- 2022
-
In: The Journal of experimental medicine. - : Rockefeller University Press. - 1540-9538 .- 0022-1007. ; 219:7
-
Journal article (peer-reviewed)abstract
- Autosomal recessive IRF7 deficiency was previously reported in three patients with single critical influenza or COVID-19 pneumonia episodes. The patients’ fibroblasts and plasmacytoid dendritic cells produced no detectable type I and III IFNs, except IFN-β. Having discovered four new patients, we describe the genetic, immunological, and clinical features of seven IRF7-deficient patients from six families and five ancestries. Five were homozygous and two were compound heterozygous for IRF7 variants. Patients typically had one episode of pulmonary viral disease. Age at onset was surprisingly broad, from 6 mo to 50 yr (mean age 29 yr). The respiratory viruses implicated included SARS-CoV-2, influenza virus, respiratory syncytial virus, and adenovirus. Serological analyses indicated previous infections with many common viruses. Cellular analyses revealed strong antiviral immunity and expanded populations of influenza- and SARS-CoV-2–specific memory CD4+ and CD8+ T cells. IRF7-deficient individuals are prone to viral infections of the respiratory tract but are otherwise healthy, potentially due to residual IFN-β and compensatory adaptive immunity.
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| 35. |
- Weinstein, John N., et al.
(author)
-
The cancer genome atlas pan-cancer analysis project
- 2013
-
In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:10, s. 1113-1120
-
Research review (peer-reviewed)abstract
- The Cancer Genome Atlas (TCGA) Research Network has profiled and analyzed large numbers of human tumors to discover molecular aberrations at the DNA, RNA, protein and epigenetic levels. The resulting rich data provide a major opportunity to develop an integrated picture of commonalities, differences and emergent themes across tumor lineages. The Pan-Cancer initiative compares the first 12 tumor types profiled by TCGA. Analysis of the molecular aberrations and their functional roles across tumor types will teach us how to extend therapies effective in one cancer type to others with a similar genomic profile. © 2013 Nature America, Inc. All rights reserved.
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| 36. |
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| 37. |
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| 38. |
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| 39. |
- Garcia-Garcia, A, et al.
(author)
-
Humans with inherited MyD88 and IRAK-4 deficiencies are predisposed to hypoxemic COVID-19 pneumonia
- 2023
-
In: The Journal of experimental medicine. - : Rockefeller University Press. - 1540-9538 .- 0022-1007. ; 220:5
-
Journal article (peer-reviewed)abstract
- X-linked recessive deficiency of TLR7, a MyD88- and IRAK-4–dependent endosomal ssRNA sensor, impairs SARS-CoV-2 recognition and type I IFN production in plasmacytoid dendritic cells (pDCs), thereby underlying hypoxemic COVID-19 pneumonia with high penetrance. We report 22 unvaccinated patients with autosomal recessive MyD88 or IRAK-4 deficiency infected with SARS-CoV-2 (mean age: 10.9 yr; 2 mo to 24 yr), originating from 17 kindreds from eight countries on three continents. 16 patients were hospitalized: six with moderate, four with severe, and six with critical pneumonia, one of whom died. The risk of hypoxemic pneumonia increased with age. The risk of invasive mechanical ventilation was also much greater than in age-matched controls from the general population (OR: 74.7, 95% CI: 26.8–207.8, P < 0.001). The patients’ susceptibility to SARS-CoV-2 can be attributed to impaired TLR7-dependent type I IFN production by pDCs, which do not sense SARS-CoV-2 correctly. Patients with inherited MyD88 or IRAK-4 deficiency were long thought to be selectively vulnerable to pyogenic bacteria, but also have a high risk of hypoxemic COVID-19 pneumonia.
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| 40. |
- Röllig, M., et al.
(author)
-
A photon dominated region code comparison study
- 2007
-
In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 467:No. 1 (May III 2007), s. 187-206
-
Journal article (peer-reviewed)abstract
- Aims.We present a comparison between independent computer codes, modeling the physics and chemistry of interstellar photon dominated regions (PDRs). Our goal was to understand the mutual differences in the PDR codes and their effects on the physical and chemical structure of the model clouds, and to converge the output of different codes to a common solution.Methods. A number of benchmark models have been created, covering low and high gas densities n = 103,105.5 cm-3 and far ultraviolet intensities $\chi$ = 10, 105 in units of the Draine field (FUV: 6
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| 41. |
- Zhang, Q, et al.
(author)
-
Autoantibodies against type I IFNs in patients with critical influenza pneumonia
- 2022
-
In: The Journal of experimental medicine. - : Rockefeller University Press. - 1540-9538 .- 0022-1007. ; 219:11
-
Journal article (peer-reviewed)abstract
- Autoantibodies neutralizing type I interferons (IFNs) can underlie critical COVID-19 pneumonia and yellow fever vaccine disease. We report here on 13 patients harboring autoantibodies neutralizing IFN-α2 alone (five patients) or with IFN-ω (eight patients) from a cohort of 279 patients (4.7%) aged 6–73 yr with critical influenza pneumonia. Nine and four patients had antibodies neutralizing high and low concentrations, respectively, of IFN-α2, and six and two patients had antibodies neutralizing high and low concentrations, respectively, of IFN-ω. The patients’ autoantibodies increased influenza A virus replication in both A549 cells and reconstituted human airway epithelia. The prevalence of these antibodies was significantly higher than that in the general population for patients <70 yr of age (5.7 vs. 1.1%, P = 2.2 × 10−5), but not >70 yr of age (3.1 vs. 4.4%, P = 0.68). The risk of critical influenza was highest in patients with antibodies neutralizing high concentrations of both IFN-α2 and IFN-ω (OR = 11.7, P = 1.3 × 10−5), especially those <70 yr old (OR = 139.9, P = 3.1 × 10−10). We also identified 10 patients in additional influenza patient cohorts. Autoantibodies neutralizing type I IFNs account for ∼5% of cases of life-threatening influenza pneumonia in patients <70 yr old.
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| 42. |
- Householder, John Ethan, et al.
(author)
-
One sixth of Amazonian tree diversity is dependent on river floodplains
- 2024
-
In: NATURE ECOLOGY & EVOLUTION. - 2397-334X.
-
Journal article (peer-reviewed)abstract
- Amazonia's floodplain system is the largest and most biodiverse on Earth. Although forests are crucial to the ecological integrity of floodplains, our understanding of their species composition and how this may differ from surrounding forest types is still far too limited, particularly as changing inundation regimes begin to reshape floodplain tree communities and the critical ecosystem functions they underpin. Here we address this gap by taking a spatially explicit look at Amazonia-wide patterns of tree-species turnover and ecological specialization of the region's floodplain forests. We show that the majority of Amazonian tree species can inhabit floodplains, and about a sixth of Amazonian tree diversity is ecologically specialized on floodplains. The degree of specialization in floodplain communities is driven by regional flood patterns, with the most compositionally differentiated floodplain forests located centrally within the fluvial network and contingent on the most extraordinary flood magnitudes regionally. Our results provide a spatially explicit view of ecological specialization of floodplain forest communities and expose the need for whole-basin hydrological integrity to protect the Amazon's tree diversity and its function.
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| 43. |
- Luize, Bruno Garcia, et al.
(author)
-
Geography and ecology shape the phylogenetic composition of Amazonian tree communities
- 2024
-
In: JOURNAL OF BIOGEOGRAPHY. - 0305-0270 .- 1365-2699.
-
Journal article (peer-reviewed)abstract
- Aim: Amazonia hosts more tree species from numerous evolutionary lineages, both young and ancient, than any other biogeographic region. Previous studies have shown that tree lineages colonized multiple edaphic environments and dispersed widely across Amazonia, leading to a hypothesis, which we test, that lineages should not be strongly associated with either geographic regions or edaphic forest types. Location: Amazonia. Taxon: Angiosperms (Magnoliids; Monocots; Eudicots). Methods: Data for the abundance of 5082 tree species in 1989 plots were combined with a mega-phylogeny. We applied evolutionary ordination to assess how phylogenetic composition varies across Amazonia. We used variation partitioning and Moran's eigenvector maps (MEM) to test and quantify the separate and joint contributions of spatial and environmental variables to explain the phylogenetic composition of plots. We tested the indicator value of lineages for geographic regions and edaphic forest types and mapped associations onto the phylogeny. Results: In the terra firme and v & aacute;rzea forest types, the phylogenetic composition varies by geographic region, but the igap & oacute; and white-sand forest types retain a unique evolutionary signature regardless of region. Overall, we find that soil chemistry, climate and topography explain 24% of the variation in phylogenetic composition, with 79% of that variation being spatially structured (R-2 = 19% overall for combined spatial/environmental effects). The phylogenetic composition also shows substantial spatial patterns not related to the environmental variables we quantified (R-2 = 28%). A greater number of lineages were significant indicators of geographic regions than forest types. Main Conclusion: Numerous tree lineages, including some ancient ones (>66 Ma), show strong associations with geographic regions and edaphic forest types of Amazonia. This shows that specialization in specific edaphic environments has played a long-standing role in the evolutionary assembly of Amazonian forests. Furthermore, many lineages, even those that have dispersed across Amazonia, dominate within a specific region, likely because of phylogenetically conserved niches for environmental conditions that are prevalent within regions.
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| 44. |
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| 45. |
- Ogishi, M, et al.
(author)
-
Impaired IL-23-dependent induction of IFN-γ underlies mycobacterial disease in patients with inherited TYK2 deficiency
- 2022
-
In: The Journal of experimental medicine. - : Rockefeller University Press. - 1540-9538 .- 0022-1007. ; 219:10
-
Journal article (peer-reviewed)abstract
- Human cells homozygous for rare loss-of-expression (LOE) TYK2 alleles have impaired, but not abolished, cellular responses to IFN-α/β (underlying viral diseases in the patients) and to IL-12 and IL-23 (underlying mycobacterial diseases). Cells homozygous for the common P1104A TYK2 allele have selectively impaired responses to IL-23 (underlying isolated mycobacterial disease). We report three new forms of TYK2 deficiency in six patients from five families homozygous for rare TYK2 alleles (R864C, G996R, G634E, or G1010D) or compound heterozygous for P1104A and a rare allele (A928V). All these missense alleles encode detectable proteins. The R864C and G1010D alleles are hypomorphic and loss-of-function (LOF), respectively, across signaling pathways. By contrast, hypomorphic G996R, G634E, and A928V mutations selectively impair responses to IL-23, like P1104A. Impairment of the IL-23–dependent induction of IFN-γ is the only mechanism of mycobacterial disease common to patients with complete TYK2 deficiency with or without TYK2 expression, partial TYK2 deficiency across signaling pathways, or rare or common partial TYK2 deficiency specific for IL-23 signaling.
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| 46. |
- ter Steege, Hans, et al.
(author)
-
Mapping density, diversity and species-richness of the Amazon tree flora
- 2023
-
In: COMMUNICATIONS BIOLOGY. - 2399-3642. ; 6:1
-
Journal article (peer-reviewed)abstract
- Using 2.046 botanically-inventoried tree plots across the largest tropical forest on Earth, we mapped tree species-diversity and tree species-richness at 0.1-degree resolution, and investigated drivers for diversity and richness. Using only location, stratified by forest type, as predictor, our spatial model, to the best of our knowledge, provides the most accurate map of tree diversity in Amazonia to date, explaining approximately 70% of the tree diversity and species-richness. Large soil-forest combinations determine a significant percentage of the variation in tree species-richness and tree alpha-diversity in Amazonian forest-plots. We suggest that the size and fragmentation of these systems drive their large-scale diversity patterns and hence local diversity. A model not using location but cumulative water deficit, tree density, and temperature seasonality explains 47% of the tree species-richness in the terra-firme forest in Amazonia. Over large areas across Amazonia, residuals of this relationship are small and poorly spatially structured, suggesting that much of the residual variation may be local. The Guyana Shield area has consistently negative residuals, showing that this area has lower tree species-richness than expected by our models. We provide extensive plot meta-data, including tree density, tree alpha-diversity and tree species-richness results and gridded maps at 0.1-degree resolution. A study mapping the tree species richness in Amazonian forests shows that soil type exerts a strong effect on species richness, probably caused by the areas of these forest types. Cumulative water deficit, tree density and temperature seasonality affect species richness at a regional scale.
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| 47. |
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| 48. |
- Zhang, Q, et al.
(author)
-
Recessive inborn errors of type I IFN immunity in children with COVID-19 pneumonia
- 2022
-
In: The Journal of experimental medicine. - : Rockefeller University Press. - 1540-9538 .- 0022-1007. ; 219:8
-
Journal article (peer-reviewed)abstract
- Recessive or dominant inborn errors of type I interferon (IFN) immunity can underlie critical COVID-19 pneumonia in unvaccinated adults. The risk of COVID-19 pneumonia in unvaccinated children, which is much lower than in unvaccinated adults, remains unexplained. In an international cohort of 112 children (<16 yr old) hospitalized for COVID-19 pneumonia, we report 12 children (10.7%) aged 1.5–13 yr with critical (7 children), severe (3), and moderate (2) pneumonia and 4 of the 15 known clinically recessive and biochemically complete inborn errors of type I IFN immunity: X-linked recessive TLR7 deficiency (7 children) and autosomal recessive IFNAR1 (1), STAT2 (1), or TYK2 (3) deficiencies. Fibroblasts deficient for IFNAR1, STAT2, or TYK2 are highly vulnerable to SARS-CoV-2. These 15 deficiencies were not found in 1,224 children and adults with benign SARS-CoV-2 infection without pneumonia (P = 1.2 × 10−11) and with overlapping age, sex, consanguinity, and ethnicity characteristics. Recessive complete deficiencies of type I IFN immunity may underlie ∼10% of hospitalizations for COVID-19 pneumonia in children.
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| 49. |
- Camara, A. R., et al.
(author)
-
LSPR-based fiber optic sensing with chemically deposited Au nanoparticles
- 2010
-
In: Latin America Optics and Photonics Conference (LAOP) 2010. - Washington, D.C. : OSA. - 9781557529039
-
Conference paper (peer-reviewed)abstract
- A refractive index fiber optic sensor based on Localized Surface Plasmon Resonance (LSPR) and specular reflection from chemically deposited gold nanoparticles has been characterized, presenting a sensitivity of 38 nm/RIU.
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| 50. |
- Gélinas-Marion, Ariane, et al.
(author)
-
Plant development in the garden pea as revealed by mutations in the Crd/PsYUC1 gene
- 2023
-
In: Genes. - : MDPI. - 2073-4425. ; 14:12
-
Journal article (peer-reviewed)abstract
- In common with other plant species, the garden pea (Pisum sativum) produces the auxin indole-3-acetic acid (IAA) from tryptophan via a single intermediate, indole-3-pyruvic acid (IPyA). IPyA is converted to IAA by PsYUC1, also known as Crispoid (Crd). Here, we extend our understanding of the developmental processes affected by the Crd gene by examining the phenotypic effects of crd gene mutations on leaves, flowers, and roots. We show that in pea, Crd/PsYUC1 is important for the initiation and identity of leaflets and tendrils, stamens, and lateral roots. We also report on aspects of auxin deactivation in pea.
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