| 1. |
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| 2. |
- Tabiri, S, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 3. |
- Bravo, L, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 4. |
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| 5. |
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| 6. |
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| 7. |
- Meyer, H., et al.
(författare)
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Overview of progress in European medium sized tokamaks towards an integrated plasma-edge/wall solution
- 2017
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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. |
- 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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| 9. |
- Labit, B., et al.
(författare)
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Dependence on plasma shape and plasma fueling for small edge-localized mode regimes in TCV and ASDEX Upgrade
- 2019
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Ingår i: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 59:8
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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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| 10. |
- Coda, S., et al.
(författare)
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Physics research on the TCV tokamak facility: From conventional to alternative scenarios and beyond
- 2019
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Ingår i: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 59:11
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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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| 11. |
- Reimerdes, H., et al.
(författare)
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Overview of the TCV tokamak experimental programme
- 2022
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Ingår i: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 62:4
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Tidskriftsartikel (refereegranskat)abstract
- The tokamak a configuration variable (TCV) continues to leverage its unique shaping capabilities, flexible heating systems and modern control system to address critical issues in preparation for ITER and a fusion power plant. For the 2019-20 campaign its configurational flexibility has been enhanced with the installation of removable divertor gas baffles, its diagnostic capabilities with an extensive set of upgrades and its heating systems with new dual frequency gyrotrons. The gas baffles reduce coupling between the divertor and the main chamber and allow for detailed investigations on the role of fuelling in general and, together with upgraded boundary diagnostics, test divertor and edge models in particular. The increased heating capabilities broaden the operational regime to include T (e)/T (i) similar to 1 and have stimulated refocussing studies from L-mode to H-mode across a range of research topics. ITER baseline parameters were reached in type-I ELMy H-modes and alternative regimes with 'small' (or no) ELMs explored. Most prominently, negative triangularity was investigated in detail and confirmed as an attractive scenario with H-mode level core confinement but an L-mode edge. Emphasis was also placed on control, where an increased number of observers, actuators and control solutions became available and are now integrated into a generic control framework as will be needed in future devices. The quantity and quality of results of the 2019-20 TCV campaign are a testament to its successful integration within the European research effort alongside a vibrant domestic programme and international collaborations.
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| 12. |
- Marco, Aitor, et al.
(författare)
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A Variable Structure Control Scheme Proposal for the Tokamak a Configuration Variable
- 2019
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Ingår i: Complexity. - : Hindawi Publishing Corporation. - 1076-2787 .- 1099-0526.
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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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| 13. |
- Coda, S., et al.
(författare)
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Overview of the TCV tokamak program : Scientific progress and facility upgrades
- 2017
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Ingår i: Nuclear Fusion. - : Institute of Physics Publishing. - 0029-5515 .- 1741-4326. ; 57:10
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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. |
- Kirk, A., et al.
(författare)
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Overview of recent physics results from MAST
- 2017
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Ingår i: Nuclear Fusion. - : IOP Publishing. - 0029-5515 .- 1741-4326. ; 57:10
-
Tidskriftsartikel (refereegranskat)abstract
- New results from MAST are presented that focus on validating models in order to extrapolate to future devices. Measurements during start-up experiments have shown how the bulk ion temperature rise scales with the square of the reconnecting field. During the current ramp-up, models are not able to correctly predict the current diffusion. Experiments have been performed looking at edge and core turbulence. At the edge, detailed studies have revealed how filament characteristics are responsible for determining the near and far scrape off layer density profiles. In the core the intrinsic rotation and electron scale turbulence have been measured. The role that the fast ion gradient has on redistributing fast ions through fishbone modes has led to a redesign of the neutral beam injector on MAST Upgrade. In H-mode the turbulence at the pedestal top has been shown to be consistent with being due to electron temperature gradient modes. A reconnection process appears to occur during edge localized modes (ELMs) and the number of filaments released determines the power profile at the divertor. Resonant magnetic perturbations can mitigate ELMs provided the edge peeling response is maximised and the core kink response minimised. The mitigation of intrinsic error fields with toroidal mode number n > 1 has been shown to be important for plasma performance.
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| 15. |
- Meyer, H., et al.
(författare)
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Overview of physics results from MAST towards ITER/DEMO and the MAST Upgrade
- 2013
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Ingår i: Nuclear Fusion. - : IOP Publishing. - 0029-5515 .- 1741-4326. ; 53:10, s. 104008-
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Tidskriftsartikel (refereegranskat)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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| 16. |
- Chapman, I. T., et al.
(författare)
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Overview of MAST results
- 2015
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Ingår i: Nuclear Fusion. - : IOP Publishing. - 0029-5515 .- 1741-4326. ; 55:10
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Tidskriftsartikel (refereegranskat)abstract
- The Mega Ampere Spherical Tokamak (MAST) programme is strongly focused on addressing key physics issues in preparation for operation of ITER as well as providing solutions for DEMO design choices. In this regard, MAST has provided key results in understanding and optimizing H-mode confinement, operating with smaller edge localized modes (ELMs), predicting and handling plasma exhaust and tailoring auxiliary current drive. In all cases, the high-resolution diagnostic capability on MAST is complemented by sophisticated numerical modelling to facilitate a deeper understanding. Mitigation of ELMs with resonant magnetic perturbations (RMPs) with toroidal mode number n(RMP) = 2, 3, 4, 6 has been demonstrated: at high and low collisionality; for the first ELM following the transition to high confinement operation; during the current ramp-up; and with rotating n(RMP) = 3 RMPs. n(RMP) = 4, 6 fields cause less rotation braking whilst the power to access H-mode is less with n(RMP) = 4 than n(RMP) = 3, 6. Refuelling with gas or pellets gives plasmas with mitigated ELMs and reduced peak heat flux at the same time as achieving good confinement. A synergy exists between pellet fuelling and RMPs, since mitigated ELMs remove fewer particles. Inter-ELM instabilities observed with Doppler backscattering are consistent with gyrokinetic simulations of micro-tearing modes in the pedestal. Meanwhile, ELM precursors have been strikingly observed with beam emission spectroscopy (BES) measurements. A scan in beta at the L-H transition shows that pedestal height scales strongly with core pressure. Gyro-Bohm normalized turbulent ion heat flux (as estimated from the BES data) is observed to decrease with increasing tilt of the turbulent eddies. Fast ion redistribution by energetic particle modes depends on density, and access to a quiescent domain with 'classical' fast ion transport is found above a critical density. Highly efficient electron Bernstein wave current drive (1 A W-1) has been achieved in solenoid-free start-up. A new proton detector has characterized escaping fusion products. Langmuir probes and a high-speed camera suggest filaments play a role in particle transport in the private flux region whilst coherence imaging has measured scrape-off layer (SOL) flows. BOUT++ simulations show that fluxes due to filaments are strongly dependent on resistivity and magnetic geometry of the SOL, with higher radial fluxes at higher resistivity. Finally, MAST Upgrade is due to begin operation in 2016 to support ITER preparation and importantly to operate with a Super-X divertor to test extended leg concepts for particle and power exhaust.
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| 17. |
- Lloyd, B., et al.
(författare)
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Overview of physics results from MAST
- 2011
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Ingår i: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 51:9, s. 094013 (paper no.)-
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Tidskriftsartikel (refereegranskat)abstract
- Major developments on the Mega Amp Spherical Tokamak (MAST) have enabled important advances in support of ITER and the physics basis of a spherical tokamak (ST) based component test facility (CTF), as well as providing new insight into underlying tokamak physics. For example, L-H transition studies benefit from high spatial and temporal resolution measurements of pedestal profile evolution (temperature, density and radial electric field) and in support of pedestal stability studies the edge current density profile has been inferred from motional Stark effect measurements. The influence of the q-profile and E x B flow shear on transport has been studied in MAST and equilibrium flow shear has been included in gyro-kinetic codes, improving comparisons with the experimental data. H-modes exhibit a weaker q and stronger collisionality dependence of heat diffusivity than implied by IPB98(gamma, 2) scaling, which may have important implications for the design of an ST-based CTF. ELM mitigation, an important issue for ITER, has been demonstrated by applying resonant magnetic perturbations (RMPs) using both internal and external coils, but full stabilization of type-I ELMs has not been observed. Modelling shows the importance of including the plasma response to the RMP fields. MAST plasmas with q > 1 and weak central magnetic shear regularly exhibit a long-lived saturated ideal internal mode. Measured plasma braking in the presence of this mode compares well with neo-classical toroidal viscosity theory. In support of basic physics understanding, high resolution Thomson scattering measurements are providing new insight into sawtooth crash dynamics and neo-classical tearing mode critical island widths. Retarding field analyser measurements show elevated ion temperatures in the scrape-off layer of L-mode plasmas and, in the presence of type-I ELMs, ions with energy greater than 500 eV are detected 20 cm outside the separatrix. Disruption mitigation by massive gas injection has reduced divertor heat loads by up to 70%.
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| 18. |
- Harrison, J.R., et al.
(författare)
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Overview of new MAST physics in anticipation of first results from MAST Upgrade
- 2019
-
Ingår i: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 59:11
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Forskningsöversikt (refereegranskat)abstract
- The mega amp spherical tokamak (MAST) was a low aspect ratio device (R/a = 0.85/0.65 ∼ 1.3) with similar poloidal cross-section to other medium-size tokamaks. The physics programme concentrates on addressing key physics issues for the operation of ITER, design of DEMO and future spherical tokamaks by utilising high resolution diagnostic measurements closely coupled with theory and modelling to significantly advance our understanding. An empirical scaling of the energy confinement time that favours higher power, lower collisionality devices is consistent with gyrokinetic modelling of electron scale turbulence. Measurements of ion scale turbulence with beam emission spectroscopy and gyrokinetic modelling in up-down symmetric plasmas find that the symmetry of the turbulence is broken by flow shear. Near the non-linear stability threshold, flow shear tilts the density fluctuation correlation function and skews the fluctuation amplitude distribution. Results from fast particle physics studies include the observation that sawteeth are found to redistribute passing and trapped fast particles injected from neutral beam injectors in equal measure, suggesting that resonances between the m = 1 perturbation and the fast ion orbits may be playing a dominant role in the fast ion transport. Measured D-D fusion products from a neutron camera and a charged fusion product detector are 40% lower than predictions from TRANSP/NUBEAM, highlighting possible deficiencies in the guiding centre approximation. Modelling of fast ion losses in the presence of resonant magnetic perturbations (RMPs) can reproduce trends observed in experiments when the plasma response and charge-exchange losses are accounted for. Measurements with a neutral particle analyser during merging-compression start-up indicate the acceleration of ions and electrons. Transport at the plasma edge has been improved through reciprocating probe measurements that have characterised a geodesic acoustic mode at the edge of an ohmic L-mode plasma and particle-in-cell modelling has improved the interpretation of plasma potential estimates from ball-pen probes. The application of RMPs leads to a reduction in particle confinement in L-mode and H-mode and an increase in the core ionization source. The ejection of secondary filaments following type-I ELMs correlates with interactions with surfaces near the X-point. Simulations of the interaction between pairs of filaments in the scrape-off layer suggest this results in modest changes to their velocity, and in most cases can be treated as moving independently. A stochastic model of scrape-off layer profile formation based on the superposition of non-interacting filaments is in good agreement with measured time-average profiles. Transport in the divertor has been improved through fast camera imaging, indicating the presence of a quiescent region devoid of filament near the X-point, extending from the separatrix to ψ n ∼ 1.02. Simulations of turbulent transport in the divertor show that the angle between the divertor leg on the curvature vector strongly influences transport into the private flux region via the interchange mechanism. Coherence imaging measurements show counter-streaming flows of impurities due to gas puffing increasing the pressure on field lines where the gas is ionised. MAST Upgrade is based on the original MAST device, with substantially improved capabilities to operate with a Super-X divertor to test extended divertor leg concepts. SOLPS-ITER modelling predicts the detachment threshold will be reduced by more than a factor of 2, in terms of upstream density, in the Super-X compared with a conventional configuration and that the radiation front movement is passively stabilised before it reaches the X-point. 1D fluid modelling reveals the key role of momentum and power loss mechanisms in governing detachment onset and evolution. Analytic modelling indicates that long legs placed at large major radius, or equivalently low at the target compared with the X-point are more amenable to external control. With MAST Upgrade experiments expected in 2019, a thorough characterisation of the sources of the intrinsic error field has been carried out and a mitigation strategy developed.
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| 19. |
- Chellaï, O., et al.
(författare)
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Millimeter-wave beam scattering and induced broadening by plasma turbulence in the TCV tokamak
- 2021
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Ingår i: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 61:6
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Tidskriftsartikel (refereegranskat)abstract
- The scattering of millimeter-wave beams from electron density fluctuations and the associated beam broadening are experimentally demonstrated. Using a dedicated setup, instantaneous deflection and (de-)focusing of the beam due to density blobs on the beam path are shown to agree with full-wave simulations. The detected time-averaged wave power transmitted through the turbulent plasma is reproduced by the radiative-transfer model implemented in the WKBeam code, which predicts a ∼50% turbulence-induced broadening of the beam cross-section. The role of core turbulence for the considered geometry is highlighted.
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| 20. |
- Haycock, Philip C., et al.
(författare)
-
Association Between Telomere Length and Risk of Cancer and Non-Neoplastic Diseases A Mendelian Randomization Study
- 2017
-
Ingår i: JAMA Oncology. - : American Medical Association. - 2374-2437 .- 2374-2445. ; 3:5, s. 636-651
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE: The causal direction and magnitude of the association between telomere length and incidence of cancer and non-neoplastic diseases is uncertain owing to the susceptibility of observational studies to confounding and reverse causation. OBJECTIVE: To conduct a Mendelian randomization study, using germline genetic variants as instrumental variables, to appraise the causal relevance of telomere length for risk of cancer and non-neoplastic diseases. DATA SOURCES: Genomewide association studies (GWAS) published up to January 15, 2015. STUDY SELECTION: GWAS of noncommunicable diseases that assayed germline genetic variation and did not select cohort or control participants on the basis of preexisting diseases. Of 163 GWAS of noncommunicable diseases identified, summary data from 103 were available. DATA EXTRACTION AND SYNTHESIS: Summary association statistics for single nucleotide polymorphisms (SNPs) that are strongly associated with telomere length in the general population. MAIN OUTCOMES AND MEASURES: Odds ratios (ORs) and 95% confidence intervals (CIs) for disease per standard deviation (SD) higher telomere length due to germline genetic variation. RESULTS: Summary data were available for 35 cancers and 48 non-neoplastic diseases, corresponding to 420 081 cases (median cases, 2526 per disease) and 1 093 105 controls (median, 6789 per disease). Increased telomere length due to germline genetic variation was generally associated with increased risk for site-specific cancers. The strongest associations (ORs [ 95% CIs] per 1-SD change in genetically increased telomere length) were observed for glioma, 5.27 (3.15-8.81); serous low-malignant-potential ovarian cancer, 4.35 (2.39-7.94); lung adenocarcinoma, 3.19 (2.40-4.22); neuroblastoma, 2.98 (1.92-4.62); bladder cancer, 2.19 (1.32-3.66); melanoma, 1.87 (1.55-2.26); testicular cancer, 1.76 (1.02-3.04); kidney cancer, 1.55 (1.08-2.23); and endometrial cancer, 1.31 (1.07-1.61). Associations were stronger for rarer cancers and at tissue sites with lower rates of stem cell division. There was generally little evidence of association between genetically increased telomere length and risk of psychiatric, autoimmune, inflammatory, diabetic, and other non-neoplastic diseases, except for coronary heart disease (OR, 0.78 [ 95% CI, 0.67-0.90]), abdominal aortic aneurysm (OR, 0.63 [ 95% CI, 0.49-0.81]), celiac disease (OR, 0.42 [ 95% CI, 0.28-0.61]) and interstitial lung disease (OR, 0.09 [ 95% CI, 0.05-0.15]). CONCLUSIONS AND RELEVANCE: It is likely that longer telomeres increase risk for several cancers but reduce risk for some non-neoplastic diseases, including cardiovascular diseases.
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| 21. |
- Guimond, S. E., et al.
(författare)
-
Synthetic Heparan Sulfate Mimetic Pixatimod (PG545) Potently Inhibits SARS-CoV-2 by Disrupting the Spike-ACE2 Interaction
- 2022
-
Ingår i: ACS Central Science. - : American Chemical Society (ACS). - 2374-7943 .- 2374-7951. ; 8:5, s. 527-545
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Tidskriftsartikel (refereegranskat)abstract
- Heparan sulfate (HS) is a cell surface polysaccharide recently identified as a coreceptor with the ACE2 protein for the S1 spike protein on SARS-CoV-2 virus, providing a tractable new therapeutic target. Clinically used heparins demonstrate an inhibitory activity but have an anticoagulant activity and are supply-limited, necessitating alternative solutions. Here, we show that synthetic HS mimetic pixatimod (PG545), a cancer drug candidate, binds and destabilizes the SARS-CoV-2 spike protein receptor binding domain and directly inhibits its binding to ACE2, consistent with molecular modeling identification of multiple molecular contacts and overlapping pixatimod and ACE2 binding sites. Assays with multiple clinical isolates of SARS-CoV-2 virus show that pixatimod potently inhibits the infection of monkey Vero E6 cells and physiologically relevant human bronchial epithelial cells at safe therapeutic concentrations. Pixatimod also retained broad potency against variants of concern (VOC) including B.1.1.7 (Alpha), B.1.351 (Beta), B.1.617.2 (Delta), and B.1.1.529 (Omicron). Furthermore, in a K18-hACE2 mouse model, pixatimod significantly reduced SARS-CoV-2 viral titers in the upper respiratory tract and virus-induced weight loss. This demonstration of potent anti-SARS-CoV-2 activity tolerant to emerging mutations establishes proof-of-concept for targeting the HS-Spike protein-ACE2 axis with synthetic HS mimetics and provides a strong rationale for clinical investigation of pixatimod as a potential multimodal therapeutic for COVID-19.
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| 22. |
- Jones, Gregory T., et al.
(författare)
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Meta-Analysis of Genome-Wide Association Studies for Abdominal Aortic Aneurysm Identifies Four New Disease-Specific Risk Loci
- 2017
-
Ingår i: Circulation Research. - 0009-7330 .- 1524-4571. ; 120:2, s. 341-
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Tidskriftsartikel (refereegranskat)abstract
- Rationale: Abdominal aortic aneurysm (AAA) is a complex disease with both genetic and environmental risk factors. Together, 6 previously identified risk loci only explain a small proportion of the heritability of AAA. Objective: To identify additional AAA risk loci using data from all available genome-wide association studies. Methods and Results: Through a meta-analysis of 6 genome-wide association study data sets and a validation study totaling 10 204 cases and 107 766 controls, we identified 4 new AAA risk loci: 1q32.3 (SMYD2), 13q12.11 (LINC00540), 20q13.12 (near PCIF1/MMP9/ZNF335), and 21q22.2 (ERG). In various database searches, we observed no new associations between the lead AAA single nucleotide polymorphisms and coronary artery disease, blood pressure, lipids, or diabetes mellitus. Network analyses identified ERG, IL6R, and LDLR as modifiers of MMP9, with a direct interaction between ERG and MMP9. Conclusions: The 4 new risk loci for AAA seem to be specific for AAA compared with other cardiovascular diseases and related traits suggesting that traditional cardiovascular risk factor management may only have limited value in preventing the progression of aneurysmal disease.
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| 23. |
- Gretarsdottir, Solveig, et al.
(författare)
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Genome-wide association study identifies a sequence variant within the DAB2IP gene conferring susceptibility to abdominal aortic aneurysm
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 42:8, s. 71-692
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Tidskriftsartikel (refereegranskat)abstract
- We performed a genome-wide association study on 1,292 individuals with abdominal aortic aneurysms (AAAs) and 30,503 controls from Iceland and The Netherlands, with a follow-up of top markers in up to 3,267 individuals with AAAs and 7,451 controls. The A allele of rs7025486 on 9q33 was found to associate with AAA, with an odds ratio (OR) of 1.21 and P = 4.6 x 10(-10). In tests for association with other vascular diseases, we found that rs7025486[A] is associated with early onset myocardial infarction (OR = 1.18, P = 3.1 x 10(-5)), peripheral arterial disease (OR = 1.14, P = 3.9 x 10(-5)) and pulmonary embolism (OR = 1.20, P = 0.00030), but not with intracranial aneurysm or ischemic stroke. No association was observed between rs7025486[A] and common risk factors for arterial and venous diseases-that is, smoking, lipid levels, obesity, type 2 diabetes and hypertension. Rs7025486 is located within DAB2IP, which encodes an inhibitor of cell growth and survival.
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| 24. |
- Helgadottir, Anna, et al.
(författare)
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Apolipoprotein(a) Genetic Sequence Variants Associated With Systemic Atherosclerosis and Coronary Atherosclerotic Burden But Not With Venous Thromboembolism
- 2012
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Ingår i: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097 .- 1558-3597. ; 60:8, s. 722-729
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Tidskriftsartikel (refereegranskat)abstract
- Objectives The purpose of this study is investigate the effects of variants in the apolipoprotein(a) gene (LPA) on vascular diseases with different atherosclerotic and thrombotic components. Background It is unclear whether the LPA variants rs10455872 and rs3798220, which correlate with lipoprotein(a) levels and coronary artery disease (CAD), confer susceptibility predominantly via atherosclerosis or thrombosis. Methods The 2 LPA variants were combined and examined as LPA scores for the association with ischemic stroke (and TOAST [Trial of Org 10172 in Acute Stroke Treatment] subtypes) (effective sample size [n(e)] = 9,396); peripheral arterial disease (n(e) = 5,215); abdominal aortic aneurysm (ne = 4,572); venous thromboembolism (ne = 4,607); intracranial aneurysm (ne = 1,328); CAD (n(e) = 12,716), carotid intima-media thickness (n = 3,714), and angiographic CAD severity (n = 5,588). Results LPA score was associated with ischemic stroke subtype large artery atherosclerosis (odds ratio [OR]: 1.27; p = 6.7 X 10(-4)), peripheral artery disease (OR: 1.47; p = 2.9 x 10(-14)), and abdominal aortic aneurysm (OR: 1.23; p = 6.0 x 10(-5)), but not with the ischemic stroke subtypes cardioembolism (OR: 1.03; p = 0.69) or small vessel disease (OR: 1.06; p = 0.52). Although the LPA variants were not associated with carotid intima-media thickness, they were associated with the number of obstructed coronary vessels (p = 4.8 x 10(-12)). Furthermore, CAD cases carrying LPA risk variants had increased susceptibility to atherosclerotic manifestations outside of the coronary tree (OR: 1.26; p = 0.0010) and had earlier onset of CAD (-1.58 years/allele; p = 8.2 x 10(-8)) than CAD cases not carrying the risk variants. There was no association of LPA score with venous thromboembolism (OR: 0.97; p = 0.63) or intracranial aneurysm (OR: 0.85; p = 0.15). Conclusions LPA sequence variants were associated with atherosclerotic burden, but not with primarily thrombotic phenotypes. (J Am Coll Cardiol 2012; 60: 722-9) (C) 2012 by the American College of Cardiology Foundation
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| 27. |
- He, H. J., et al.
(författare)
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Multilaboratory Assessment of a New Reference Material for Quality Assurance of Cell-Free Tumor DNA Measurements
- 2019
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Ingår i: Journal of Molecular Diagnostics. - : Elsevier BV. - 1525-1578. ; 21:4, s. 658-676
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Tidskriftsartikel (refereegranskat)abstract
- We conducted a multilaboratory assessment to determine the suitability of a new commercially available reference material with 40 cancer variants in a background of wild-type DNA at four different variant allele frequencies (VAFs): 2%, 0.50%, 0.125%, and 0%. The variants include single nucleotides, insertions, deletions, and two structural variations selected for their clinical importance and to challenge the performance of next-generation sequencing (NGS) methods. Fragmented DNA was formulated to simulate the size distribution of circulating wild-type and tumor DNA in a synthetic plasma matrix. DNA was extracted from these samples and characterized with different methods and multiple laboratories. The various extraction methods had differences in yield, perhaps because of differences in chemistry. Digital PCR assays were used to measure VAFs to compare results from different NGS methods. Comparable VAFs were observed across the different NGS methods. This multilaboratory assessment demonstrates that the new reference material is an appropriate tool to determine the analytical parameters of different measurement methods and to ensure their quality assurance.
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| 28. |
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| 29. |
- Olff, M., et al.
(författare)
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Screening for consequences of trauma–an update on the global collaboration on traumatic stress
- 2020
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Ingår i: European Journal of Psychotraumatology. - : Taylor and Francis Ltd.. - 2000-8198 .- 2000-8066. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- This letter provides an update on the activities of “The Global Collaboration on Traumatic Stress†(GC-TS) as first described by Schnyder et al. in 2017. It presents in further detail the projects of the first theme, in particular the development of and initial data on the Global Psychotrauma Screen (GPS), a brief instrument designed to screen for the wide range of potential outcomes of trauma. English language data and ongoing studies in several languages provide a first indication that the GPS is a feasible, reliable and valid tool, a tool that may be very useful in the current pandemic of the coronavirus disease 2019 (COVID-19). Further multi-language and cross-cultural validation is needed. Since the start of the GC-TS, new themes have been introduced to focus on in the coming years: a) Forcibly displaced persons, b) Global prevalence of stress and trauma related disorders, c) Socio-emotional development across cultures, and d) Collaborating to make traumatic stress research data “FAIRâ€. The most recent theme added is that of Global crises, currently focusing on COVID-19-related projects.
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| 30. |
- Cecconello, Marco, et al.
(författare)
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First observations of confined fast ions in MAST Upgrade with an upgraded neutron camera
- 2023
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Ingår i: Plasma Physics and Controlled Fusion. - : Institute of Physics Publishing (IOPP). - 0741-3335 .- 1361-6587. ; 65:3
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Tidskriftsartikel (refereegranskat)abstract
- Spherical tokamaks are key to the successful design of operating scenarios of future fusion reactors in the areas of divertor physics, neutral beam current drive and fast ion physics. MAST Upgrade, which has successfully concluded its first experimental campaign, was specifically designed to address the role of the radial gradient of the fast ion distribution in driving the excitation of magneto-hydrodynamic (MHD) instabilities, such as toroidal Alfven eigenmodes, fish-bones and long-lived mode, thanks to its two tangential neutral beam injection systems, one on the equatorial plane and one that is vertically shifted 65 cm above the equatorial plane. To study the fast ion dynamics in the presence of such instabilities, as well as of sawteeth and neo-classical tearing modes, several fast ion diagnostics were upgraded and new ones added. Among them, the MAST prototype neutron camera (NC) has been upgraded to six, equatorial sight-lines. The first observations of the confined fast ion behavior with the upgraded NC in a wide range of plasma scenarios characterized by on-axis and/or off-axis heating and different MHD instabilities are presented here. The observations presented in this study confirm previous results on MAST but with a higher level of detail and highlight new physics observations unique to the MAST Upgrade. The results presented here confirm the improved performance of the NC Upgrade, which thus becomes one of the key elements, in combination with the rich set of fast ion diagnostics available on the MAST Upgrade, for a more constrained modeling of the fast ion dynamics in fusion reactor relevant scenarios.
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| 31. |
- Vallurupalli, M., et al.
(författare)
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Students for global oncology: Building a movement for student education and engagement in an emerging field
- 2015
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Ingår i: Annals of Global Health. - : Ubiquity Press, Ltd.. - 2214-9996. ; 81:1, s. 56-56
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Program/Project Purpose: Increased recognition of the global cancer burden and inequalities in care and outcomes have led to the growing field of global oncology, focused on strengthening health systems to improve cancer prevention and care. Motivated students and trainees are in need of pathways to approach these challenges. In 2012, Harvard Medical students formed Students for Global Oncology (S4GO), an adjunct to the larger inter-professional organization Global Oncology. The group had three aims: 1) connect students with mentors in the field, 2) develop novel approaches in global oncology, and 3) disseminate global oncology knowledge. Structure/Method/Design: S4GO has created content and organized events to increase awareness about the global cancer burden, while promoting trainee opportunities in research and practical hands-on projects. Engagement was enhanced by mentorship from more senior students and faculty, to interface with existing global oncology projects. Outcomes & Evaluation: Since 2012, S4GO has grown from two to 68 students. Currently, new chapters at seven other institutions in the US and Canada are being developed. As of October 2014, S4GO has developed a case-based cancer care delivery curriculum with six case-based seminars, along with numerous blog entries and interviews of leading researchers in the field of global oncology, all available on the S4GO website. Students have completed projects in over nine countries and are actively involved in technological and on-the-ground efforts to develop creative solutions and collaborations aimed at easing the global cancer burden. Held in February 2014, the inaugural student-led global oncology symposium involved 200 individuals from across the world, including leaders in global health, pharmaceutical industry, public policy and cancer care. This symposium has been viewed by hundreds online and has fostered novel collaborations and projects focused on enhancing cancer care delivery. Going Forward: In the coming years, S4GO will continue efforts to build awareness and catalyze creative solutions for cancer care in resource-limited settings. These efforts will increase exposure for novel and successful student efforts as well as intra-institutional and intra-professional activity.
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| 34. |
- Lind, Lars, et al.
(författare)
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Key Characteristics of Cardiovascular Toxicants
- 2021
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Ingår i: Journal of Environmental Health Perspectives. - : US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE. - 0091-6765 .- 1552-9924. ; 129:9
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The concept of chemical agents having properties that confer potential hazard called key characteristics (KCs) was first developed to identify carcinogenic hazards. Identification of KCs of cardiovascular (CV) toxicants could facilitate the systematic assessment of CV hazards and understanding of assay and data gaps associated with current approaches. OBJECTIVES: We sought to develop a consensus-based synthesis of scientific evidence on the KCs of chemical and nonchemical agents known to cause CV toxicity along with methods to measure them. METHODS: An expert working group was convened to discuss mechanisms associated with CV toxicity. RESULTS: The group identified 12 KCs of CV toxicants, defined as exogenous agents that adversely interfere with function of the CV system. The KCs were organized into those primarily affecting cardiac tissue (numbers 1-4 below), the vascular system (5-7), or both (8-12), as follows: 1) impairs regulation of cardiac excitability, 2) impairs cardiac contractility and relaxation, 3) induces cardiomyocyte injury and death, 4) induces proliferation of valve stroma, 5) impacts endothelial and vascular function, 6) alters hemostasis, 7) causes dyslipidemia, 8) impairs mitochondrial function, 9) modifies autonomic nervous system activity, 10) induces oxidative stress, 11) causes inflammation, and 12) alters hormone signaling. DISCUSSION: These 12 KCs can be used to help identify pharmaceuticals and environmental pollutants as CV toxicants, as well as to better understand the mechanistic underpinnings of their toxicity. For example, evidence exists that fine particulate matter [PM <= 2.5 mu m in aerodynamic diameter (PM2.5)] air pollution, arsenic, anthracycline drugs, and other exogenous chemicals possess one or more of the described KCs. In conclusion, the KCs could be used to identify potential CV toxicants and to define a set of test methods to evaluate CV toxicity in a more comprehensive and standardized manner than current approaches.
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