This review summarizes surface morphology changes of tungsten caused by heat and particle loadings from edge plasmas, and their effects on enhanced erosion and material lifetime in ITER and beyond. ...Pulsed heat loadings by transients (disruption and ELM) are the largest concerns due to surface melting, cracking, and dust formation. Hydrogen induced blistering is unlikely to be an issue of ITER. Helium bombardment would cause surface morphology changes such as W fuzz, He holes, and nanometric bubble layers, which could lead to enhanced erosion (e.g. unipolar arcing of W fuzz). Particle loadings could enhance pulsed heat effects (cracking and erosion) due to surface layer embrittlement by nanometric bubbles and solute atoms. But pulsed heat loadings alleviate surfaces morphology changes in some cases (He holes by ELM-like heat pulses). Effects of extremely high fluence (∼1030m−2), mixed materials, and neutron irradiation are important issues to be pursued for ITER and beyond. In addition, surface refurbishment to prolong material lifetime is also an important issue.
Component development for operation in a large-scale fusion device requires thorough testing and qualification for the intended operational conditions. In particular environments are necessary which ...are comparable to the real operation conditions, allowing at the same time for in situ/in vacuo diagnostics and flexible operation, even beyond design limits during the testing. Various electron and neutral particle devices provide the capabilities for high heat load tests, suited for material samples and components from lab-scale dimensions up to full-size parts, containing toxic materials like beryllium, and being activated by neutron irradiation. To simulate the conditions specific to a fusion plasma both at the first wall and in the divertor of fusion devices, linear plasma devices allow for a test of erosion and hydrogen isotope recycling behavior under well-defined and controlled conditions. Finally, the complex conditions in a fusion device (including the effects caused by magnetic fields) are exploited for component and material tests by exposing test mock-ups or material samples to a fusion plasma by manipulator systems. They allow for easy exchange of test pieces in a tokamak or stellarator device, without opening the vessel. Such a chain of test devices and qualification procedures is required for the development of plasma-facing components which then can be successfully operated in future fusion power devices. The various available as well as newly planned devices and test stands, together with their specific capabilities, are presented in this manuscript. Results from experimental programs on test facilities illustrate their significance for the qualification of plasma-facing materials and components. An extended set of references provides access to the current status of material and component testing capabilities in the international fusion programs.
Crack formation in an ITER-reference tungsten grade was examined under single thermal shock loading. Typically two sorts of cracks, major cracks and microcracks, were observed at the loaded surfaces. ...The microstructures were quantified and the formation mechanisms were discussed. The major cracks were generated due to the brittleness of the tungsten material and microcracks were formed in a process which was initiated by plastic deformation at high temperature. The plastic deformation caused also surface elevation of the loaded area. At more intense thermal shock loading conditions, the microcracks disappeared and surface modifications due to recrystallization was observed.
Drug treatment of 3D cancer spheroids more accurately reflects in vivo therapeutic responses compared to adherent culture studies. In EGFR-mutated lung adenocarcinoma, EGFR-TKIs show enhanced ...efficacy in spheroid cultures. Simultaneous inhibition of multiple parallel RTKs further enhances EGFR-TKI effectiveness. We show that the common RTK signaling intermediate SOS1 was required for 3D spheroid growth of EGFR-mutated NSCLC cells. Using two distinct measures of pharmacologic synergy, we demonstrated that SOS1 inhibition strongly synergized with EGFR-TKI treatment only in 3D spheroid cultures. Combined EGFR- and SOS1-inhibition markedly inhibited Raf/MEK/ERK and PI3K/AKT signaling. Finally, broad assessment of the pharmacologic landscape of drug-drug interactions downstream of mutated EGFR revealed synergy when combining an EGFR-TKI with inhibitors of proximal signaling intermediates SOS1 and SHP2, but not inhibitors of downstream RAS effector pathways. These data indicate that vertical inhibition of proximal EGFR signaling should be pursued as a potential therapy to treat EGFR-mutated tumors.
In this work two simulation methods for transient events on tungsten are compared. ELM-like thermal shock tests were performed with the electron beam device JUDITH 1 and a pulsed Nd:YAG laser on pure ...tungsten. The major difference between these two simulation methods is the surface near volumetric loading in case of the e-beam while the penetration depth of photons is negligible. Beside the definition of damage threshold values special attention was paid to the analysis of induced damages like surface modifications and crack formation. The obtained results indicate that there are no qualitative differences in the damage behaviour and the damage threshold values of tungsten for both simulation techniques. Slight differences of crack parameters are a result of geometric effects due to differences of the exposed areas. A more distinct impact results from the fast scanning of the sample (e-beam) in contrast to the homogenous loading (laser) which results in different surface modification.
► Tungsten and CFC were subjected to transient high cycle heat loads. ► Tungsten showed fatigue damage (roughening, cracking, melting). ► Roughening occurred as precursor for cracking. ► Underlying ...mechanism depended on surface temperature. ► CFC showed 3× higher damage threshold and no long term fatigue mechanism.
Within the ITER divertor lifetime millions of transient events are expected during H-mode operation due to edge localized modes (type I ELMs). These will deposit their energy on plasma facing materials that are pre-heated to various surface temperatures, depending on the steady state heat load (SSHL) at the respective location, leading to synergistic effects. An electron beam facility was used to simulate ELM-like heat loads with ITER relevant power densities (≈0.5GW/m2) and pulse duration (0.5ms). At the same time additional SSHL was applied to obtain different base temperatures. Experiments were performed on actively cooled pure tungsten and the carbon fiber composite (CFC) NB41, applying 103–106 pulses of 0.5ms duration with a power density of 0.14–0.55GW/m2 and 0.55–0.68GW/m2 on tungsten and CFC, respectively. Surface temperatures were about 200°C, 400°C and 700°C for tungsten and about 450°C for CFC. Crack formation in tungsten was preceded by roughening due to plastic deformation. In case of Tsurf≈200°C cracks propagated comparably fast (brittle material), while slow propagation and recrystallization around the crack edges indicated fatigue damage at higher temperatures. Compared to tungsten, CFC showed a higher damage threshold.
Fungi in the genus Pneumocystis cause pneumonia (PCP) in hosts with debilitated immune systems and are emerging as co-morbidity factors associated with chronic diseases such as COPD. Limited ...therapeutic choices and poor understanding of the life cycle are a result of the inability of these fungi to grow outside the mammalian lung. Within the alveolar lumen, Pneumocystis spp., appear to have a bi-phasic life cycle consisting of an asexual phase characterized by binary fission of trophic forms and a sexual cycle resulting in formation of cysts, but the life cycle stage that transmits the infection is not known. The cysts, but not the trophic forms, express beta -1,3-D-glucan synthetase and contain abundant beta -1,3-D-glucan. Here we show that therapeutic and prophylactic treatment of PCP with echinocandins, compounds which inhibit the synthesis of beta -1,3-D-glucan, depleted cysts in rodent models of PCP, while sparing the trophic forms which remained in significant numbers. Survival was enhanced in the echincandin treated mice, likely due to the decreased beta -1,3-D-glucan content in the lungs of treated mice and rats which coincided with reductions of cyst numbers, and dramatic remodeling of organism morphology. Strong evidence for the cyst as the agent of transmission was provided by the failure of anidulafungin-treated mice to transmit the infection. We show for the first time that withdrawal of anidulafungin treatment with continued immunosuppression permitted the repopulation of cyst forms. Treatment of PCP with an echinocandin alone will not likely result in eradication of infection and cessation of echinocandin treatment while the patient remains immunosuppressed could result in relapse. Importantly, the echinocandins provide novel and powerful chemical tools to probe the still poorly understood bi-phasic life cycle of this genus of fungal pathogens.
The anisotropy of the magnetoviscous effect (MVE) of a cobalt ferrofluid has been studied in a slit die viscometer for three orientations of the applied magnetic field: in the direction of the fluid ...flow (Δη1), the velocity gradient (Δη2), and the vorticity (Δη3). The majority of the cobalt particles in the ferrofluid exhibit a strong dipole–dipole interaction, which corresponds to a weighted interaction parameter of λw≈10.6. Thus the particles form extended microstructures inside the fluid which lead to enhanced MVE ratios Δη2/Δη1>3 and Δη3/Δη1>0.3 even for strong shearing and weak magnetic fields compared to fluids which contain non-interacting spherical particles with Δη2/Δη1≈1 and Δη3/Δη1=0. Furthermore, a non-monotonic increase has been observed in the shear thinning behavior of Δη2 for weak magnetic fields <10kA/m, which cannot be explained solely by the magnetization of individual particles and the formation and disintegration of linear particle chains but indicates the presence of heterophase structures.
•The magnetoviscous effect in a ferrofluid with strong interaction is anisotropic.•The strongest effects are found in a magnetic field parallel to the shear gradient.•In strong magnetic fields the microstructure of the fluid is stable against shearing.•In weak fields the fluid behavior indicates the presence of heterophase structures.
Objective
The cerebellum is involved in cognitive processing and emotion control. Cerebellar alterations could explain symptoms of schizophrenia spectrum disorder (SZ) and bipolar disorder (BD). In ...addition, literature suggests that lithium might influence cerebellar anatomy. Our aim was to study cerebellar anatomy in SZ and BD, and investigate the effect of lithium.
Methods
Participants from 7 centers worldwide underwent a 3T MRI. We included 182 patients with SZ, 144 patients with BD, and 322 controls. We automatically segmented the cerebellum using the CERES pipeline. All outputs were visually inspected.
Results
Patients with SZ showed a smaller global cerebellar gray matter volume compared to controls, with most of the changes located to the cognitive part of the cerebellum (Crus II and lobule VIIb). This decrease was present in the subgroup of patients with recent‐onset SZ. We did not find any alterations in the cerebellum in patients with BD. However, patients medicated with lithium had a larger size of the anterior cerebellum, compared to patients not treated with lithium.
Conclusion
Our multicenter study supports a distinct pattern of cerebellar alterations in SZ and BD.
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