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Sökning: WFRF:(Marini M.) > (2015-2019)

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1.
  • 2017
  • swepub:Mat__t
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2.
  • Aad, G, et al. (författare)
  • 2015
  • swepub:Mat__t
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3.
  • 2018
  • Ingår i: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 58:1
  • Forskningsöversikt (refereegranskat)
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4.
  • Bombarda, F., et al. (författare)
  • Runaway electron beam control
  • 2019
  • Ingår i: Plasma Physics and Controlled Fusion. - : IOP Publishing. - 1361-6587 .- 0741-3335. ; 61:1
  • Tidskriftsartikel (refereegranskat)
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5.
  • 2018
  • Ingår i: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 58:9
  • Tidskriftsartikel (refereegranskat)
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6.
  • Meyer, H., et al. (författare)
  • Overview of progress in European medium sized tokamaks towards an integrated plasma-edge/wall solution
  • 2017
  • Ingår i: Nuclear Fusion. - : Institute of Physics Publishing (IOPP). - 0029-5515 .- 1741-4326. ; 57:10
  • Tidskriftsartikel (refereegranskat)abstract
    • Integrating the plasma core performance with an edge and scrape-off layer (SOL) that leads to tolerable heat and particle loads on the wall is a major challenge. The new European medium size tokamak task force (EU-MST) coordinates research on ASDEX Upgrade (AUG), MAST and TCV. This multi-machine approach within EU-MST, covering a wide parameter range, is instrumental to progress in the field, as ITER and DEMO core/pedestal and SOL parameters are not achievable simultaneously in present day devices. A two prong approach is adopted. On the one hand, scenarios with tolerable transient heat and particle loads, including active edge localised mode (ELM) control are developed. On the other hand, divertor solutions including advanced magnetic configurations are studied. Considerable progress has been made on both approaches, in particular in the fields of: ELM control with resonant magnetic perturbations (RMP), small ELM regimes, detachment onset and control, as well as filamentary scrape-off-layer transport. For example full ELM suppression has now been achieved on AUG at low collisionality with n = 2 RMP maintaining good confinement H-H(98,H-y2) approximate to 0.95. Advances have been made with respect to detachment onset and control. Studies in advanced divertor configurations (Snowflake, Super-X and X-point target divertor) shed new light on SOL physics. Cross field filamentary transport has been characterised in a wide parameter regime on AUG, MAST and TCV progressing the theoretical and experimental understanding crucial for predicting first wall loads in ITER and DEMO. Conditions in the SOL also play a crucial role for ELM stability and access to small ELM regimes.
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7.
  • Meyer, H., et al. (författare)
  • Overview of progress in European medium sized tokamaks towards an integrated plasma-edge/wall solution
  • 2017
  • Ingår i: Nuclear Fusion. - : Institute of Physics Publishing (IOPP). - 0029-5515 .- 1741-4326. ; 57:10
  • Tidskriftsartikel (refereegranskat)abstract
    • Integrating the plasma core performance with an edge and scrape-off layer (SOL) that leads to tolerable heat and particle loads on the wall is a major challenge. The new European medium size tokamak task force (EU-MST) coordinates research on ASDEX Upgrade (AUG), MAST and TCV. This multi-machine approach within EU-MST, covering a wide parameter range, is instrumental to progress in the field, as ITER and DEMO core/pedestal and SOL parameters are not achievable simultaneously in present day devices. A two prong approach is adopted. On the one hand, scenarios with tolerable transient heat and particle loads, including active edge localised mode (ELM) control are developed. On the other hand, divertor solutions including advanced magnetic configurations are studied. Considerable progress has been made on both approaches, in particular in the fields of: ELM control with resonant magnetic perturbations (RMP), small ELM regimes, detachment onset and control, as well as filamentary scrape-off-layer transport. For example full ELM suppression has now been achieved on AUG at low collisionality with n = 2 RMP maintaining good confinement H-H(98,H-y2) approximate to 0.95. Advances have been made with respect to detachment onset and control. Studies in advanced divertor configurations (Snowflake, Super-X and X-point target divertor) shed new light on SOL physics. Cross field filamentary transport has been characterised in a wide parameter regime on AUG, MAST and TCV progressing the theoretical and experimental understanding crucial for predicting first wall loads in ITER and DEMO. Conditions in the SOL also play a crucial role for ELM stability and access to small ELM regimes.
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8.
  • Labit, B., et al. (författare)
  • Dependence on plasma shape and plasma fueling for small edge-localized mode regimes in TCV and ASDEX Upgrade
  • 2019
  • Ingår i: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 59:8
  • Tidskriftsartikel (refereegranskat)abstract
    • © 2019 Institute of Physics Publishing. All rights reserved. Within the EUROfusion MST1 work package, a series of experiments has been conducted on AUG and TCV devices to disentangle the role of plasma fueling and plasma shape for the onset of small ELM regimes. On both devices, small ELM regimes with high confinement are achieved if and only if two conditions are fulfilled at the same time. Firstly, the plasma density at the separatrix must be large enough (ne,sep/nG ∼ 0.3), leading to a pressure profile flattening at the separatrix, which stabilizes type-I ELMs. Secondly, the magnetic configuration has to be close to a double null (DN), leading to a reduction of the magnetic shear in the extreme vicinity of the separatrix. As a consequence, its stabilizing effect on ballooning modes is weakened.
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9.
  • Abdellaoui, G., et al. (författare)
  • Meteor studies in the framework of the JEM-EUSO program
  • 2017
  • Ingår i: Planetary and Space Science. - : Elsevier. - 0032-0633 .- 1873-5088. ; 143, s. 245-255
  • Tidskriftsartikel (refereegranskat)abstract
    • We summarize the state of the art of a program of UV observations from space of meteor phenomena, a secondary objective of the JEM-EUSO international collaboration. Our preliminary analysis indicates that JEM-EUSO, taking advantage of its large FOV and good sensitivity, should be able to detect meteors down to absolute magnitude close to 7. This means that JEM-EUSO should be able to record a statistically significant flux of meteors, including both sporadic ones, and events produced by different meteor streams. Being unaffected by adverse weather conditions, JEM-EUSO can also be a very important facility for the detection of bright meteors and fireballs, as these events can be detected even in conditions of very high sky background. In the case of bright events, moreover, exhibiting some persistence of the meteor train, preliminary simulations show that it should be possible to exploit the motion of the ISS itself and derive at least a rough 3D reconstruction of the meteor trajectory. Moreover, the observing strategy developed to detect meteors may also be applied to the detection of nuclearites, exotic particles whose existence has been suggested by some theoretical investigations. Nuclearites are expected to move at higher velocities than meteoroids, and to exhibit a wider range of possible trajectories, including particles moving upward after crossing the Earth. Some pilot studies, including the approved Mini-EUSO mission, a precursor of JEM-EUSO, are currently operational or in preparation. We are doing simulations to assess the performance of Mini-EUSO for meteor studies, while a few meteor events have been already detected using the ground-based facility EUSO-TA.
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10.
  • Abdellaoui, G., et al. (författare)
  • First observations of speed of light tracks by a fluorescence detector looking down on the atmosphere
  • 2018
  • Ingår i: Journal of Instrumentation. - : IOP PUBLISHING LTD. - 1748-0221. ; 13
  • Tidskriftsartikel (refereegranskat)abstract
    • EUSO-Balloon is a pathfinder mission for the Extreme Universe Space Observatory onboard the Japanese Experiment Module (JEM-EUSO). It was launched on the moonless night of the 25(th) of August 2014 from Timmins, Canada. The flight ended successfully after maintaining the target altitude of 38 km for five hours. One part of the mission was a 2.5 hour underflight using a helicopter equipped with three UV light sources (LED, xenon flasher and laser) to perform an inflight calibration and examine the detectors capability to measure tracks moving at the speed of light. We describe the helicopter laser system and details of the underflight as well as how the laser tracks were recorded and found in the data. These are the first recorded laser tracks measured from a fluorescence detector looking down on the atmosphere. Finally, we present a first reconstruction of the direction of the laser tracks relative to the detector.
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11.
  • Coda, S., et al. (författare)
  • Physics research on the TCV tokamak facility: From conventional to alternative scenarios and beyond
  • 2019
  • Ingår i: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 59:11
  • Tidskriftsartikel (refereegranskat)abstract
    • The research program of the TCV tokamak ranges from conventional to advanced-tokamak scenarios and alternative divertor configurations, to exploratory plasmas driven by theoretical insight, exploiting the device's unique shaping capabilities. Disruption avoidance by real-time locked mode prevention or unlocking with electron-cyclotron resonance heating (ECRH) was thoroughly documented, using magnetic and radiation triggers. Runaway generation with high-Z noble-gas injection and runaway dissipation by subsequent Ne or Ar injection were studied for model validation. The new 1 MW neutral beam injector has expanded the parameter range, now encompassing ELMy H-modes in an ITER-like shape and nearly non-inductive H-mode discharges sustained by electron cyclotron and neutral beam current drive. In the H-mode, the pedestal pressure increases modestly with nitrogen seeding while fueling moves the density pedestal outwards, but the plasma stored energy is largely uncorrelated to either seeding or fueling. High fueling at high triangularity is key to accessing the attractive small edge-localized mode (type-II) regime. Turbulence is reduced in the core at negative triangularity, consistent with increased confinement and in accord with global gyrokinetic simulations. The geodesic acoustic mode, possibly coupled with avalanche events, has been linked with particle flow to the wall in diverted plasmas. Detachment, scrape-off layer transport, and turbulence were studied in L- and H-modes in both standard and alternative configurations (snowflake, super-X, and beyond). The detachment process is caused by power 'starvation' reducing the ionization source, with volume recombination playing only a minor role. Partial detachment in the H-mode is obtained with impurity seeding and has shown little dependence on flux expansion in standard single-null geometry. In the attached L-mode phase, increasing the outer connection length reduces the in-out heat-flow asymmetry. A doublet plasma, featuring an internal X-point, was achieved successfully, and a transport barrier was observed in the mantle just outside the internal separatrix. In the near future variable-configuration baffles and possibly divertor pumping will be introduced to investigate the effect of divertor closure on exhaust and performance, and 3.5 MW ECRH and 1 MW neutral beam injection heating will be added.
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12.
  • Marini, S., et al. (författare)
  • Association of Apolipoprotein E With Intracerebral Hemorrhage Risk by Race/Ethnicity A Meta-analysis
  • 2019
  • Ingår i: Jama Neurology. - : American Medical Association (AMA). - 2168-6149 .- 2168-6157. ; 76:4, s. 480-491
  • Tidskriftsartikel (refereegranskat)abstract
    • IMPORTANCE Genetic studies of intracerebral hemorrhage (ICH) have focused mainly on white participants, but genetic risk may vary or could be concealed by differing nongenetic coexposures in nonwhite populations. Transethnic analysis of risk may clarify the role of genetics in ICH risk across populations. OBJECTIVE To evaluate associations between established differences in ICH risk by race/ethnicity and the variability in the risks of apolipoprotein E (APOE) epsilon 4 alleles, the most potent genetic risk factor for ICH. DESIGN, SETTING, AND PARTICIPANTS This case-control study of primary ICH meta-analyzed the association of APOE allele status on ICH risk, applying a 2-stage clustering approach based on race/ethnicity and stratified by a contributing study. A propensity score analysis was used to model the association of APOE with the burden of hypertension across race/ethnic groups. Primary ICH cases and controls were collected from 3 hospital- and population-based studies in the United States and 8 in European sites in the International Stroke Genetic Consortium. Participants were enrolled from January 1, 1999, to December 31, 2017. Participants with secondary causes of ICH were excluded from enrollment. Controls were regionally matched within each participating study. MAIN OUTCOMES AND MEASURES Clinical variables were systematically obtained from structured interviews within each site. APOE genotype was centrally determined for all studies. RESULTS In total, 13 124 participants (7153 [54.5%] male with a median [interquartile range] age of 66 [56-76] years) were included. In white participants, APOE epsilon 2 (odds ratio [OR], 1.49; 95% CI, 1.24-1.80; P < .001) and APOE epsilon 4 (OR, 1.51; 95% CI, 1.23-1.85; P < .001) were associated with lobar ICH risk; however, within self-identified Hispanic and black participants, no associations were found. After propensity score matching for hypertension burden, APOE epsilon 4 was associated with lobar ICH risk among Hispanic (OR, 1.14; 95% CI, 1.03-1.28; P = .01) but not in black (OR, 1.02; 95% CI, 0.98-1.07; P = .25) participants. APOE epsilon 2 and epsilon 4 did not show an association with nonlobar ICH risk in any race/ethnicity. CONCLUSIONS AND RELEVANCE APOE epsilon 4 and epsilon 2 alleles appear to affect lobar ICH risk variably by race/ethnicity, associations that are confirmed in white individuals but can be shown in Hispanic individuals only when the excess burden of hypertension is propensity score-matched; further studies are needed to explore the interactions between APOE alleles and environmental exposures that vary by race/ethnicity in representative populations at risk for ICH.
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13.
  • Coda, S., et al. (författare)
  • Overview of the TCV tokamak program : Scientific progress and facility upgrades
  • 2017
  • Ingår i: Nuclear Fusion. - : Institute of Physics Publishing. - 0029-5515 .- 1741-4326. ; 57:10
  • Tidskriftsartikel (refereegranskat)abstract
    • The TCV tokamak is augmenting its unique historical capabilities (strong shaping, strong electron heating) with ion heating, additional electron heating compatible with high densities, and variable divertor geometry, in a multifaceted upgrade program designed to broaden its operational range without sacrificing its fundamental flexibility. The TCV program is rooted in a three-pronged approach aimed at ITER support, explorations towards DEMO, and fundamental research. A 1 MW, tangential neutral beam injector (NBI) was recently installed and promptly extended the TCV parameter range, with record ion temperatures and toroidal rotation velocities and measurable neutral-beam current drive. ITER-relevant scenario development has received particular attention, with strategies aimed at maximizing performance through optimized discharge trajectories to avoid MHD instabilities, such as peeling-ballooning and neoclassical tearing modes. Experiments on exhaust physics have focused particularly on detachment, a necessary step to a DEMO reactor, in a comprehensive set of conventional and advanced divertor concepts. The specific theoretical prediction of an enhanced radiation region between the two X-points in the low-field-side snowflake-minus configuration was experimentally confirmed. Fundamental investigations of the power decay length in the scrape-off layer (SOL) are progressing rapidly, again in widely varying configurations and in both D and He plasmas; in particular, the double decay length in L-mode limited plasmas was found to be replaced by a single length at high SOL resistivity. Experiments on disruption mitigation by massive gas injection and electron-cyclotron resonance heating (ECRH) have begun in earnest, in parallel with studies of runaway electron generation and control, in both stable and disruptive conditions; a quiescent runaway beam carrying the entire electrical current appears to develop in some cases. Developments in plasma control have benefited from progress in individual controller design and have evolved steadily towards controller integration, mostly within an environment supervised by a tokamak profile control simulator. TCV has demonstrated effective wall conditioning with ECRH in He in support of the preparations for JT-60SA operation.
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14.
  • Marco, Aitor, et al. (författare)
  • A Variable Structure Control Scheme Proposal for the Tokamak a Configuration Variable
  • 2019
  • Ingår i: Complexity. - : Hindawi Publishing Corporation. - 1076-2787 .- 1099-0526.
  • Tidskriftsartikel (refereegranskat)abstract
    • Fusion power is the most significant prospects in the long-term future of energy in the sense that it composes a potentially clean, cheap, and unlimited power source that would substitute the widespread traditional nonrenewable energies, reducing the geographical dependence on their sources as well as avoiding collateral environmental impacts. Although the nuclear fusion research started in the earlier part of 20th century and the fusion reactors have been developed since the 1950s, the fusion reaction processes achieved have not yet obtained net power, since the generated plasma requires more energy to achieve and remain in necessary particular pressure and temperature conditions than the produced profitable energy. For this purpose, the plasma has to be confined inside a vacuum vessel, as it is the case of the Tokamak reactor, which consists of a device that generates magnetic fields within a toroidal chamber, being one of the most promising solutions nowadays. However, the Tokamak reactors still have several issues such as the presence of plasma instabilities that provokes a decay of the fusion reaction and, consequently, a reduction in the pulse duration. In this sense, since long pulse reactions are the key to produce net power, the use of robust and fast controllers arises as a useful tool to deal with the unpredictability and the small time constant of the plasma behavior. In this context, this article focuses on the application of robust control laws to improve the controllability of the plasma current, a crucial parameter during the plasma heating and confinement processes. In particular, a variable structure control scheme based on sliding surfaces, namely, a sliding mode controller (SMC) is presented and applied to the plasma current control problem. In order to test the validity and goodness of the proposed controller, its behavior is compared to that of the traditional PID schemes applied in these systems, using the RZIp model for the Tokamak a Configuration Variable (TCV) reactor. The obtained results are very promising, leading to consider this controller as a strong candidate to enhance the performance of the PID-based controllers usually employed in this kind of systems.
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15.
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16.
  • Jurado, B., et al. (författare)
  • Investigation of the surrogate-reaction method via the simultaneous measurement of gamma-emission and fission probabilities
  • 2017
  • Ingår i: EPJ Web of Conferences. - : EDP Sciences. - 2101-6275 .- 2100-014X. ; 146
  • Konferensbidrag (refereegranskat)abstract
    • We present the results of two experiments where we have measured for the first time simultaneously the fission and gamma-decay probabilities induced by different surrogate reactions. In particular, we have investigated the 238 U(d,p), 238 U( 3 He,t) and 238 U( 3 He, 4 He) reactions as surrogates for the neutron-induced n + 238 U, n + 237 Np and n + 236 U reactions, respectively. In the region where gamma emission, neutron emission and fission compete, our results for the fission probabilities agree fairly well with the neutron-induced data, whereas our gamma-decay probabilities are significantly higher than the neutron-induced data. The interpretation of these results is not obvious and is discussed within the framework of the statistical model with preliminary results for calculated spin-parity distributions populated in surrogate reactions. We also present future plans for surrogate-reaction studies in inverse kinematics with radioactive-ion beams at storage rings.
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17.
  • Lolli, M. L., et al. (författare)
  • Bioisosteres of Indomethacin as Inhibitors of Aldo-Keto Reductase 1C3
  • 2019
  • Ingår i: Acs Medicinal Chemistry Letters. - : American Chemical Society (ACS). - 1948-5875. ; 10:4, s. 437-443
  • Tidskriftsartikel (refereegranskat)abstract
    • Aldo-keto reductase 1C3 (AKR1C3) is an attractive target in drug design for its role in resistance to anticancer therapy. Several nonsteroidal anti-inflammatory drugs such as indomethacin are known to inhibit AKR1C3 in a nonselective manner because of COX-off target effects. Here we designed two indomethacin analogues by proposing a bioisosteric connection between the indomethacin carboxylic acid function and either hydroxyfurazan or hydroxy triazole rings. Both compounds were found to target AKR1C3 in a selective manner. In particular, hydroxyfurazan derivative is highly selective for AKR1C3 over the 1C2 isoform (up to 90-times more) and inactive on COX enzymes. High-resolution crystal structure of its complex with AKR1C3 shed light onto the binding mode of the new inhibitors. In cell-based assays (on colorectal and prostate cancer cells), the two indomethacin analogues showed higher potency than indomethacin. Therefore, these two AKR1C3 inhibitors can be used to provide further insight into the role of AKR1C3 in cancer. © 2019 American Chemical Society.
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18.
  • Marini, Sandro, et al. (författare)
  • 17p12 Influences Hematoma Volume and Outcome in Spontaneous Intracerebral Hemorrhage
  • 2018
  • Ingår i: Stroke. - 0039-2499. ; 49:7, s. 1618-1625
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and Purpose-Hematoma volume is an important determinant of clinical outcome in spontaneous intracerebral hemorrhage (ICH). We performed a genome-wide association study (GWAS) of hematoma volume with the aim of identifying novel biological pathways involved in the pathophysiology of primary brain injury in ICH. Methods-We conducted a 2-stage (discovery and replication) case-only genome-wide association study in patients with ICH of European ancestry. We utilized the admission head computed tomography to calculate hematoma volume via semiautomated computer-Assisted technique. After quality control and imputation, 7 million genetic variants were available for association testing with ICH volume, which was performed separately in lobar and nonlobar ICH cases using linear regression. Signals with P<5×10- 8 were pursued in replication and tested for association with admission Glasgow coma scale and 3-month post-ICH dichotomized (0-2 versus 3-6) modified Rankin Scale using ordinal and logistic regression, respectively. Results-The discovery phase included 394 ICH cases (228 lobar and 166 nonlobar) and identified 2 susceptibility loci: A genomic region on 22q13 encompassing PARVB (top single-nucleotide polymorphism rs9614326: β, 1.84; SE, 0.32; P=4.4×10-8) for lobar ICH volume and an intergenic region overlying numerous copy number variants on 17p12 (top single-nucleotide polymorphism rs11655160: β, 0.95; SE, 0.17; P=4.3×10-8) for nonlobar ICH volume. The replication included 240 ICH cases (71 lobar and 169 nonlobar) and corroborated the association for 17p12 (P=0.04; meta-Analysis P=2.5×10-9; heterogeneity, P=0.16) but not for 22q13 (P=0.49). In multivariable analysis, rs11655160 was also associated with lower admission Glasgow coma scale (odds ratio, 0.17; P=0.004) and increased risk of poor 3-month modified Rankin Scale (odds ratio, 1.94; P=0.045). Conclusions-We identified 17p12 as a novel susceptibility risk locus for hematoma volume, clinical severity, and functional outcome in nonlobar ICH. Replication in other ethnicities and follow-up translational studies are needed to elucidate the mechanism mediating the observed association.
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19.
  • Illuminati, S., et al. (författare)
  • In-situ trace metal (Cd, Pb, Cu) speciation along the Po River plume (Northern Adriatic Sea) using submersible systems
  • 2019
  • Ingår i: Marine Chemistry. - : Elsevier BV. - 0304-4203. ; 212, s. 47-63
  • Tidskriftsartikel (refereegranskat)abstract
    • Information on the distribution and speciation of trace metals is of critical importance for our ability to interpret the links between the bioavailability and uptake of an element, and its biogeochemical cycle in coastal environments. Within the framework of the European Project "In-situ automated Monitoring of Trace metal speciation in Estuaries and Coastal zones in relation with the biogeochemical processes (IMTEC)", the chemical speciation of Cd, Pb and Cu was carried out along the Po River plume in the period 27 October - 2 November 2002. During the cruise, five Voltammetric In-situ Profiling systems and one Multi Physical Chemical Profiler, as well as conventional voltammetric instruments, were successfully applied in order to evaluate the distribution of Cd, Pb and Cu between different fractions (free ion, dynamic, colloidal, dissolved and particulate fractions) and to assess the evolution of these fractions during estuarine mixing and in the water column. Dynamic concentrations were 0.05-0.2 nmol L-1 Cd, 0.02-0.2 nmol L-1 Pb, and 0.15-4.0 nmol L-1 Cu. Cd was mainly present as dynamic fraction (40-100% of the dissolved Cd). High proportions of Pb (similar to 70%) and Cu (similar to 80%) were present as colloids probably of biogenic origin. Principal components analysis reveals a strong influence of the Po River discharge on the spatial and vertical distributions of metal species. Almost all the metal fractions globally decreased following the salinity gradient. Metal concentrations are far below (at least one order of magnitude lower) the Environmental Quality Standard established by the Italian law. However, the Cu dynamic fraction showed concentrations likely to be toxic to sensitive phytoplankton community and to have negative effects on larva development of coastal macroinvertebrate species (toxicity data extracted from literature).
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20.
  • Oberstedt, S., et al. (författare)
  • Prompt fission gamma-ray spectra characteristics - a first summary
  • 2015
  • Ingår i: Physics Procedia. - : Elsevier BV. - 1875-3884 .- 1875-3892. ; 64, s. 83-90
  • Konferensbidrag (refereegranskat)abstract
    • In this work we give an overview of our investigations of prompt gamma-ray emission in nuclear fission. This work was conducted during the last five years in response to a high priority nuclear data request formulated by the OECD/NEA. The aim was to reveal data deficiencies responsible for a severe under-prediction of the prompt gamma heating in nuclear reactor cores. We obtained new prompt fission gamma-ray spectral (PFGS) data for Cf-252(SF) as well as for thermal-neutron induced fission on U-235(nth,f) and Pu-241(nth,f). In addition, first PFGS measurements with a fast-neutron beam were accomplished, too. The impact of the new data and future data needs are discussed.
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21.
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23.
  • Chung, Jaeyoon, et al. (författare)
  • Genome-wide association study of cerebral small vessel disease reveals established and novel loci
  • 2019
  • Ingår i: Brain : a journal of neurology. - : Oxford University Press (OUP). - 1460-2156. ; 142:10, s. 3176-3189
  • Tidskriftsartikel (refereegranskat)abstract
    • Intracerebral haemorrhage and small vessel ischaemic stroke (SVS) are the most acute manifestations of cerebral small vessel disease, with no established preventive approaches beyond hypertension management. Combined genome-wide association study (GWAS) of these two correlated diseases may improve statistical power to detect novel genetic factors for cerebral small vessel disease, elucidating underlying disease mechanisms that may form the basis for future treatments. Because intracerebral haemorrhage location is an adequate surrogate for distinct histopathological variants of cerebral small vessel disease (lobar for cerebral amyloid angiopathy and non-lobar for arteriolosclerosis), we performed GWAS of intracerebral haemorrhage by location in 1813 subjects (755 lobar and 1005 non-lobar) and 1711 stroke-free control subjects. Intracerebral haemorrhage GWAS results by location were meta-analysed with GWAS results for SVS from MEGASTROKE, using 'Multi-Trait Analysis of GWAS' (MTAG) to integrate summary data across traits and generate combined effect estimates. After combining intracerebral haemorrhage and SVS datasets, our sample size included 241 024 participants (6255 intracerebral haemorrhage or SVS cases and 233 058 control subjects). Genome-wide significant associations were observed for non-lobar intracerebral haemorrhage enhanced by SVS with rs2758605 [MTAG P-value (P) = 2.6 × 10-8] at 1q22; rs72932727 (P = 1.7 × 10-8) at 2q33; and rs9515201 (P = 5.3 × 10-10) at 13q34. In the GTEx gene expression library, rs2758605 (1q22), rs72932727 (2q33) and rs9515201 (13q34) are significant cis-eQTLs for PMF1 (P = 1 × 10-4 in tibial nerve), NBEAL1, FAM117B and CARF (P < 2.1 × 10-7 in arteries) and COL4A2 and COL4A1 (P < 0.01 in brain putamen), respectively. Leveraging S-PrediXcan for gene-based association testing with the predicted expression models in tissues related with nerve, artery, and non-lobar brain, we found that experiment-wide significant (P < 8.5 × 10-7) associations at three genes at 2q33 including NBEAL1, FAM117B and WDR12 and genome-wide significant associations at two genes including ICA1L at 2q33 and ZCCHC14 at 16q24. Brain cell-type specific expression profiling libraries reveal that SEMA4A, SLC25A44 and PMF1 at 1q22 and COL4A1 and COL4A2 at 13q34 were mainly expressed in endothelial cells, while the genes at 2q33 (FAM117B, CARF and NBEAL1) were expressed in various cell types including astrocytes, oligodendrocytes and neurons. Our cross-phenotype genetic study of intracerebral haemorrhage and SVS demonstrates novel genome-wide associations for non-lobar intracerebral haemorrhage at 2q33 and 13q34. Our replication of the 1q22 locus previous seen in traditional GWAS of intracerebral haemorrhage, as well as the rediscovery of 13q34, which had previously been reported in candidate gene studies with other cerebral small vessel disease-related traits strengthens the credibility of applying this novel genome-wide approach across intracerebral haemorrhage and SVS.
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24.
  • Dainese, Matteo, et al. (författare)
  • Landscape simplification weakens the association between terrestrial producer and consumer diversity in Europe
  • 2017
  • Ingår i: Global Change Biology. - : Wiley. - 1354-1013 .- 1365-2486. ; 23:8, s. 3040-3051
  • Tidskriftsartikel (refereegranskat)abstract
    • Land-use change is one of the primary drivers of species loss, yet little is known about its effect on other components of biodiversity that may be at risk. Here, we ask whether, and to what extent, landscape simplification, measured as the percentage of arable land in the landscape, disrupts the functional and phylogenetic association between primary producers and consumers. Across seven European regions, we inferred the potential associations (functional and phylogenetic) between host plants and butterflies in 561 seminatural grasslands. Local plant diversity showed a strong bottom-up effect on butterfly diversity in the most complex landscapes, but this effect disappeared in simple landscapes. The functional associations between plant and butterflies are, therefore, the results of processes that act not only locally but are also dependent on the surrounding landscape context. Similarly, landscape simplification reduced the phylogenetic congruence among host plants and butterflies indicating that closely related butterflies become more generalist in the resources used. These processes occurred without any detectable change in species richness of plants or butterflies along the gradient of arable land. The structural properties of ecosystems are experiencing substantial erosion, with potentially pervasive effects on ecosystem functions and future evolutionary trajectories. Loss of interacting species might trigger cascading extinction events and reduce the stability of trophic interactions, as well as influence the longer term resilience of ecosystem functions. This underscores a growing realization that species richness is a crude and insensitive metric and that both functional and phylogenetic associations, measured across multiple trophic levels, are likely to provide additional and deeper insights into the resilience of ecosystems and the functions they provide.
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25.
  • Santoru, A, et al. (författare)
  • A new potassium-based intermediate and its role in the desorption properties of the K-Mg-N-H system.
  • 2016
  • Ingår i: Physical chemistry chemical physics : PCCP. - : Royal Society of Chemistry (RSC). - 1463-9084 .- 1463-9076. ; 18:5, s. 3910-3920
  • Tidskriftsartikel (refereegranskat)abstract
    • New insights into the reaction pathways of different potassium/magnesium amide-hydride based systems are discussed. In situ SR-PXD experiments were for the first time performed in order to reveal the evolution of the phases connected with the hydrogen releasing processes. Evidence of a new K-N-H intermediate is shown and discussed with particular focus on structural modification. Based on these results, a new reaction mechanism of amide-hydride anionic exchange is proposed.
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