Diacylglycerol regulates acute hypoxic pulmonary vasoconstriction via TRPC6

Background: Hypoxic pulmonary vasoconstriction (HPV) is an essential mechanism of the lung that matches blood perfusion to alveolar ventilation to optimize gas exchange. Recently we have demonstrated that acute but not sustained HPV is critically dependent on the classical transient receptor potential 6 (TRPC6) channel. However, the mechanism of TRPC6 activation during acute HPV remains elusive. We hypothesize that a diacylglycerol (DAG)-dependent activation of TRPC6 regulates acute HPV. Methods: We investigated the effect of the DAG analog 1-oleoyl-2-acetyl-sn-glycerol (OAG) on normoxic vascular tone in isolated perfused and ventilated mouse lungs from TRPC6-deficient and wild-type mice. Moreover, the effects of OAG, the DAG kinase inhibitor R59949 and the phospholipase C inhibitor U73122 on the strength of HPV were investigated compared to those on non-hypoxia-induced vasoconstriction elicited by the thromboxane mimeticum U46619. Results: OAG increased normoxic vascular tone in lungs from wild-type mice, but not in lungs from TRPC6-deficient mice. Under conditions of repetitive hypoxic ventilation, OAG as well as R59949 dose-dependently attenuated the strength of acute HPV whereas U46619-induced vasoconstrictions were not reduced. Like OAG, R59949 mimicked HPV, since it induced a dose-dependent vasoconstriction during normoxic ventilation. In contrast, U73122, a blocker of DAG synthesis, inhibited acute HPV whereas U73343, the inactive form of U73122, had no effect on HPV. Conclusion: These findings support the conclusion that the TRPC6-dependency of acute HPV is induced via DAG

Analysis of Dietz`s single, rectangular pulse theory for the generation of radiation via photoelectrons

The generation of radiation via photoelectrons induced off of a conducting surface has been analytically modeled and computationally simulated by several researchers. This paper analyzes and compares Dietz`s theory predictions with my research to form a unified foundation of consistent, inter-supporting results that should provide confidence in the independently performed basic research and resulting scaling laws and predictions. In doing so, this paper concentrated on Dietz`s small-spot, single, rectangular, ``weak`` pulse theory and equations, which involve nonrelativistic, monoenergetic photoelectrons emitted normal to a conducting surface in vacuum. In this paper I: (1) analytically compare Dietz`s theory equations with my theory equations, (2) compare Dietz`s theoretical scaling laws with my Particle-In-Cell (PIC) code simulation results, and (3) make Dietz`s equations easier to use in predicting and optimizing photoelectron-generated radiation. As a result, it is shown that Dietz`s equations match my theory`s equations in their predicted scaling laws, differing only slightly in their coefficients and unique model parameters. Also, Dietz`s equations generally agree with the PIC code results. Finally, optimization analysis showed that theoretical conversion efficiencies for typical real metals can meet and exceed values of 10{sup {minus}5} if optimal photon energies of 15 to 20 eV are used. Even better efficiencies should be possible if the small-spot constraint is violated as well

Particle-In-Cell (PIC) code simulation results and comparison with theory scaling laws for photoelectron-generated radiation

The generation of radiation via photoelectrons induced off of a conducting surface was explored using Particle-In-Cell (PIC) code computer simulations. Using the MAGIC PIC code, the simulations were performed in one dimension to handle the diverse scale lengths of the particles and fields in the problem. The simulations involved monoenergetic, nonrelativistic photoelectrons emitted normal to the illuminated conducting surface. A sinusoidal, 100% modulated, 6.3263 ns pulse train, as well as unmodulated emission, were used to explore the behavior of the particles, fields, and generated radiation. A special postprocessor was written to convert the PIC code simulated electron sheath into far-field radiation parameters by means of rigorous retarded time calculations. The results of the small-spot PIC simulations were used to generate various graphs showing resonance and nonresonance radiation quantities such as radiated lobe patterns, frequency, and power. A database of PIC simulation results was created and, using a nonlinear curve-fitting program, compared with theoretical scaling laws. Overall, the small-spot behavior predicted by the theoretical scaling laws was generally observed in the PIC simulation data, providing confidence in both the theoretical scaling laws and the PIC simulations

A simple model for determining photoelectron-generated radiation scaling laws

The generation of radiation via photoelectrons induced off of a conducting surface was explored using a simple model to determine fundamental scaling laws. The model is one-dimensional (small-spot) and uses monoenergetic, nonrelativistic photoelectrons emitted normal to the illuminated conducting surface. Simple steady-state radiation, frequency, and maximum orbital distance equations were derived using small-spot radiation equations, a sin{sup 2} type modulation function, and simple photoelectron dynamics. The result is a system of equations for various scaling laws, which, along with model and user constraints, are simultaneously solved using techniques similar to linear programming. Typical conductors illuminated by low-power sources producing photons with energies less than 5.0 eV are readily modeled by this small-spot, steady-state analysis, which shows they generally produce low efficiency ({eta}{sub rsL}<10{sup {minus}10.5}) pure photoelectron-induced radiation. However, the small-spot theory predicts that the total conversion efficiency for incident photon power to photoelectron-induced radiated power can go higher than 10{sup {minus}5.5} for typical real conductors if photons having energies of 15 eV and higher are used, and should go even higher still if the small-spot limit of this theory is exceeded as well. Overall, the simple theory equations, model constraint equations, and solution techniques presented provide a foundation for understanding, predicting, and optimizing the generated radiation, and the simple theory equations provide scaling laws to compare with computational and laboratory experimental data