Background— Acetyltransferase p300 is essential for cardiac development and is thought to be involved in cardiac myocyte growth through MEF2- and GATA4-dependent transcription. However, the importance of p300 in the modulation of cardiac growth in vivo is unknown. Methods and Results— Pressure overload induced by transverse aortic coarctation, postnatal physiological growth, and human heart failure were associated with large increases in p300. Minimal transgenic overexpression of p300 (1.5- to 3.5-fold) induced striking myocyte and cardiac hypertrophy. Both mortality and cardiac mass were directly related to p300 protein dosage. Heterozygous loss of a single p300 allele reduced pressure overload–induced hypertrophy by ≈50% and rescued the hypertrophic phenotype of p300 overexpressers. Increased p300 expression had no effect on total histone deacetylase activity but was associated with proportional increases in p300 acetyltransferase activity and acetylation of the p300 substrates histone 3 and GATA-4. Remarkably, a doubling of p300 levels was associated with the de novo acetylation of MEF2. Consistent with this, genes specifically upregulated in p300 transgenic hearts were highly enriched for MEF2 binding sites. Conclusions— Small increments in p300 are necessary and sufficient to drive myocardial hypertrophy, possibly through acetylation of MEF2 and upstream of signals promoting phosphorylation or nuclear export of histone deacetylases. We propose that induction of myocardial p300 content is a primary rate-limiting event in the response to hemodynamic loading in vivo and that p300 availability drives and constrains adaptive myocardial growth. Specific reduction of p300 content or activity may diminish stress-induced hypertrophy and forestall the development of heart failure.
This work studies the region of nanoparticle growth in atmospheric pressure carbon arc.Detection of the nanoparticles is realized via the planar laser induced incandescence (PLII) approach.Measurements revealed large clouds of nanoparticles in the arc periphery, bordering the region with high density of diatomic carbon molecules. Two-dimensional computational fluid dynamic simulations of the arc combined with thermodynamic modeling explain these results due to interplay of the condensation of carbon molecular species and the convection flow pattern. The results have shown that the nanoparticles are formed in the colder, outside regions of the arc and described the parameters necessary for coagulation.
An adjusted form of thermionic emission is applied to calculate emitted current from laser-heated nanoparticles and to interpret time-resolved laser-induced incandescence (TR-LII) signals. This adjusted form of thermionic emission predicts significantly lower values of emitted current compared to the commonly used Richardson-Dushman equation, since the buildup of positive charge in a laser-heated nanoparticle increases the energy barrier for further emission of electrons. Thermionic emission influences the particle's energy balance equation, which can influence TR-LII signals. Additionally, reports suggest that thermionic emission can induce disintegration of nanoparticle aggregates when the electrostatic Coulomb repulsion energy between two positively charged primary particles is greater than the van der Waals bond energy. Since the presence and size of aggregates strongly influences the particle's energy balance equation, using an appropriate form of thermionic emission to calculate emitted current may improve interpretation of TR-LII signals.
The sheared-flow stabilized (SFS) Z-pinch has demonstrated long-lived plasmas with fusion-relevant parameters. This Letter presents the first experimental results demonstrating sustained, quasi-steady-state neutron production from the Fusion Z-pinch Experiment (FuZE), operated with a mixture of 20% deuterium/80% hydrogen by volume. Neutron emissions lasting approximately 5 µs are reproducibly observed with pinch currents of approximately 200 kA during an approximately 16 µs period of plasma quiescence. The average neutron yield is estimated to be (1.25 ± 0.45) × 10 5 neutrons/pulse and scales with the square of the deuterium concentration. Coincident with the neutron signal, plasma temperatures of 1 − 2 keV, and densities of approximately 10 17 cm −3 with 0.3 cm pinch radii are measured with fully-integrated diagnostics.
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