AMP-activated protein kinase (AMPK) is an evolutionarily conserved energy sensor important for cell growth, proliferation, survival, and metabolic regulation. Active AMPK inhibits biosynthetic ...enzymes like mTOR and acetyl CoA carboxylase (required for protein and lipid synthesis, respectively) to ensure that cells maintain essential nutrients and energy during metabolic crisis. Despite our knowledge about this incredibly important kinase, no specific chemical inhibitors are available to examine its function. However, one small molecule known as compound C (also called dorsomorphin) has been widely used in cell-based, biochemical, and in vivo assays as a selective AMPK inhibitor. In nearly all these reports including a recent study in glioma, the biochemical and cellular effects of compound C have been attributed to its inhibitory action toward AMPK. While examining the status of AMPK activation in human gliomas, we observed that glioblastomas express copious amount of active AMPK. Compound C effectively reduced glioma viability in vitro both by inhibiting proliferation and inducing cell death. As expected, compound C inhibited AMPK; however, all the antiproliferative effects of this compound were AMPK independent. Instead, compound C killed glioma cells by multiple mechanisms, including activation of the calpain/cathepsin pathway, inhibition of AKT, mTORC1/C2, cell-cycle block at G2-M, and induction of necroptosis and autophagy. Importantly, normal astrocytes were significantly less susceptible to compound C. In summary, compound C is an extremely potent antiglioma agent but we suggest that caution should be taken in interpreting results when this compound is used as an AMPK inhibitor.
•Reported thin-film evaporation in the absence of nucleate boiling.•Developed a semi-analytical predictive thermal–fluidic model for the dryout heat flux.•Developed a thermal resistance model for ...superheat.
The generation of concentrated heat loads in advanced microprocessors, GaN electronics, and solar cells present significant thermal management challenges in defense, space and commercial applications. Liquid to vapor phase-change strategies are promising due to the high latent heat of vaporization of the working fluid. In particular, thin-film evaporation has received increased interest owing to advances in micro/nanofabrication and the potential to dissipate high heat fluxes by increasing the evaporative meniscus area. Yet, predictive tools to design various wicking structures are limited due to the complexity of the thermal–fluidic transport. In this work, we performed systematic experiments to characterize capillary-limited thin-film evaporation from silicon micropillar wicks in the absence of nucleate boiling. The insights gained from experiments were used to model the capillary pressure, permeability, and thermal resistance. Accordingly, we developed a semi-analytical model to determine the capillary-limited dryout heat flux and wall temperature with ±20% accuracy, compared to our experiments. The model provides a versatile platform to design and optimize micropillar wicks for next generation thermal management devices.
We investigate the reactive flash sintering of Mg0.2Ni0.2Co0.2Cu0.2Zn0.2O precursor powders prepared by a polymeric synthesis route. The flash experiments were performed at a constant heating rate of ...10 °C min−1 with electric fields from 15 to 60 V cm−1. The single-phase rock-salt structure was obtained in just a few seconds at furnace temperatures as low as 500 °C, under an electric field of 60 V cm−1 and a current density of 150 mA mm−2. Success at processing an entropy-driven phase in a remarkably short time and low furnace temperature demonstrates the potential of reactive flash sintering for producing entropy-stabilized materials.
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We describe a new system for flash sintering where a reactor is built with walls made from dog‐bone specimens that are held in Stage III of flash under current control. The reactor is placed within a ...cylindrical space, like a tube, with axial access, for camera, pyrometer, and optical spectrometer. A free‐floating green sample (without electrodes) is placed within; it is physically separated from the walls of the reactor. In the present experiments, the reactor wall as well as the “touch free” workpiece were constituted from yttria‐stabilized zirconia. The workpiece is shown to flash, luminesce, and sinter (in a few seconds) when a modest magnetic field is superimposed over the reactor. The final density depends on the strength of the magnetic field, eventually rising to ∼98%. The grain size is highly uniform and nanoscale. Samples of different and arbitrary three‐dimensional shapes have been so sintered. We propose that the walls of the reactor, which are in a constant state of flash, may generate an evanescent plasma that becomes concentrated around the center line of the reactor by the applied magnetic field. The plasma field helps to transfer energy from the reactor walls into the green sample. When the magnetic induction is turned on, the conductive load of the reactor walls on the power supply increases proving the presence of an energy transfer mechanism. The question of impedance matching between the walls, the specimen, and the free space in between is outlined.
We show that powder pressed specimens of nickel can be sintered to 99.96% density by injecting electrical current, without the use of a furnace. Full sintering could be accomplished in 10 to 52 s by ...changing the current rate from 5 to 1 A/s. In all instances, the samples sintered abruptly at a current density of ∼20 A mm−2. The grain size of the sintered samples was somewhat larger than the nickel powder particle size (∼60 μm vs. 40 μm). Tensile testing yielded a yield strength of 98 MPa, ultimate tensile stress of 323 MPa, and ductility of ∼17%. Four in‐operando measurements are reported: (i) sintering, (ii) the change in resistance with current density, (iii) the temperature, and (iv) electroluminescence. The change in resistance during flash sintering exhibited a high peak followed by a steep decline in resistance; the transient is attributed to the breakdown of particle–particle interface resistance. The same cycle repeated with the flash‐sintered, dense sample, did not show the spike, and gave reproducible results. The resistance data for these latter cycles, when viewed as a function of temperature exhibited sigmoidal behavior: initially lower, and then higher than the literature values. This unusual behavior reflects the influence of defects generated during flash. We have also measured the endothermic enthalpy, expressed by the difference between the in situ input electrical energy and the radiation, convection, and specific heat losses. Dividing by the formation energy of Frenkel pairs yields the concentration of defects, estimated to be 0.3–0.4 mol %. These concentrations are far above thermal equilibrium; it is concluded that flash of metals is a far from equilibrium phenomenon.
We show that flash-sintering in MgO-doped alumina is accompanied by a sharp increase in electrical conductivity. Experiments that measure conductivity in fully dense specimens, prepared by ...conventional sintering, prove that this is not a cause-and-effect relationship, but instead that the concomitant increase in the sintering rate and the conductivity share a common mechanism. The underlying mechanism, however, is mystifying since electrical conductivity is controlled by the transport of the fastest moving charged species, while sintering, which requires molecular transport or chemical diffusion, is limited by the slow moving charged species. Joule heating of the specimen during flash sintering cannot account for the anomalously high sintering rates. The sintering behavior of MgO-doped alumina is compared to that of nominally pure-alumina: the differences provide insight into the underlying mechanism for flash-sintering. We show that the pre-exponential in the Arrhenius equation for conductivity is enhanced in the non-linear regime, while the activation energy remains unchanged. The nucleation of Frenkel pairs is proposed as a mechanism to explain the coupling between flash-sintering and the non-linear increase in the conductivity.
We report on the discharge of the capacitance formed at the electrodes in flash experiments with yttria stabilized zirconia. The experiments were carried out by disconnecting the current, and, ...instead, short circuiting the electrodes through a resistor. The time dependent voltage across the resistor was measured; the ratio yielded the discharge current. The current decayed exponentially with time, as expected in an RC circuit, which allowed the measurement of the capacitance. Experiments were carried out in two ways. In one case the specimens were flashed within a glove box filled with Ar (< 1 ppm O2): these yielded electronic conductors. In the other case the specimens were flashed in ambient air: while electronically conducting in‐flash these specimens recover their prior insulating behavior as soon as the current is turned off. The stored charge was two orders of magnitude greater in the Ar experiments. Rather unexpectedly, the sign of the voltage expressed at the electrodes was opposite in experiments carried out in air and in Ar. The capacitance measured in the discharge experiments is attributed to the formation of space charge adjacent to the electrodes. In the case of Ar experiments, the capacitance is very large, approaching 1 F; in this case the space charge is expected to be constituted from ions. In the air experiments the specimen becomes insulating, trapping the electrons as a space charge. Hall effect measurements of the carrier density and X‐ray photoelectron spectroscopy characterization of electronically conducting single crystal specimen of cubic zirconia are reported.
It is known that once flash has been triggered with furnace heating, specimens can be held in the state of constant flash, or Stage III, outside the furnace at ambient temperature. The flash is ...maintained by the current flowing through the specimen. We show that this in‐flash state is further preserved when the specimen is immersed into liquid nitrogen. Furthermore, we show that the nature of the material existing in Stage III can be quenched by turning off the power to the specimen while it is still in immersion. Normally, during furnace cool, the specimens revert to their original state when the flash is turned off. However, yttria‐stabilized zirconia retrieved from in‐flash immersion‐and‐quench is discovered to be electronically conductive at room temperature, at approximately 11 S/m. The conductivity declines somewhat when the specimen is heated slightly above room temperature, suggesting metal‐like behavior. These in‐flash immersed specimens, with their Stage III structure frozen in place, will enable ex‐situ characterization of changes in the crystallographic, chemical, defect and electronic structure induced by flash activation.
A single‐crystal specimen of rutile (titania) was flashed repetitively, while increasing the electric field after each cycle. As expected, the flash onset temperature continued to drop modestly at ...higher fields. However, when the field was increased from 400 to 450 V cm–1, the flashed onset fell dramatically down to room temperature. We have investigated the electrical and optical properties of this room temperature flashed specimen (called SZ). The specimen was electronically conducting. Optical absorption spectroscopy revealed a narrow band of new energy levels that were generated just below the conduction band. The gap between the conduction band and this flash‐induced energy level agreed with the peak in the electroluminescence spectrum. Optical second harmonic generation (SHG) is reported. The flash‐on condition significantly lowered the SHG, which rebounded when the flash was turned off. This result suggests that the structure becomes more centrosymmetric in the state of flash, which may represent a disordered state of defects. The possibility of studying flash behavior at room temperature, without a furnace (as in SZ type specimens), opens a considerable simplification for in‐situ characterization of flash behavior. For example, a possible relationship between memristor physics and the flash phenomenon can be studied.
Joule heating during flash-sintering Raj, Rishi
Journal of the European Ceramic Society,
August 2012, 2012-8-00, Letnik:
32, Številka:
10
Journal Article
Recenzirano
Flash-sintering is invariably accompanied by a highly non-linear rise in the specimen's conductivity. Thus the specimen temperature rises above the furnace temperature. It is shown that ...flash-sintering is a transient phenomenon, where the power dissipation rises quickly at first, but then declines towards a steady state, as the power supply switches from voltage to current control. The area under the power spike, which is equal to the Joules expended in the sample during the transient, is absorbed by the heat capacity of the specimen. Therefore, the specimen temperature rises gradually towards this steady state through the transient. Whereas the power spike can exceed a peak value of 1000mWmm−3, the dissipation during the current controlled regime is in the 100–400mWmm−3 range. The extrapolation of sintering time from a few hours, as in conventional sintering, to a few seconds, using the activation energy for diffusion, predicts sample temperatures that are far in excess of the measured specimen temperature during flash sintering.
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