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Neuroreceptor activation by vibration-assisted tunneling.

ABSTRACT: G protein-coupled receptors (GPCRs) constitute a large family of receptor proteins that sense molecular signals on the exterior of a cell and activate signal transduction pathways within the cell. Modeling how an agonist activates such a receptor is fundamental for an understanding of a wide variety of physiological processes and it is of tremendous value for pharmacology and drug design. Inelastic electron tunneling spectroscopy (IETS) has been proposed as a model for the mechanism by which olfactory GPCRs are activated by a bound agonist. We apply this hyothesis to GPCRs within the mammalian nervous system using quantum chemical modeling. We found that non-endogenous agonists of the serotonin receptor share a particular IET spectral aspect both amongst each other and with the serotonin molecule: a peak whose intensity scales with the known agonist potencies. We propose an experiential validation of this model by utilizing lysergic acid dimethylamide (DAM-57), an ergot derivative, and its deuterated isotopologues; we also provide theoretical predictions for comparison to experiment. If validated our theory may provide new avenues for guided drug design and elevate methods of in silico potency/activity prediction.

SUBMITTER: Hoehn RD

PROVIDER: S-EPMC4408984 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:The presence of defects, such as pores, in materials processed using additive manufacturing represents a challenge during the manufacturing of many engineering components. Recently, ultrasonic vibration-assisted (UV-A) directed energy deposition (DED) has been shown to reduce porosity, promote grain refinement, and enhance mechanical performance in metal components. Whereas it is evident that the formation of such microstructural features is affected by the melt pool behavior, the specific mechanisms by which ultrasonic vibration (UV) influences the melt pool remain elusive. In the present investigation, UV was applied in situ to DED of 316L stainless steel single tracks and bulk parts. For the first time, high-speed video imaging and thermal imaging were implemented in situ to quantitatively correlate the application of UV to melt pool evolution in DED. Extensive imaging data were coupled with in-depth microstructural characterization to develop a statistically robust dataset describing the observed phenomena. Our findings show that UV increases the melt pool peak temperature and dimensions, while improving the wettability of injected particles with the melt pool surface and reducing particle residence time. Near the substrate, we observe that UV results in a 92% decrease in porosity, and a 54% decrease in dendritic arm spacing. The effect of UV on the melt pool is caused by the combined mechanisms of acoustic cavitation, ultrasound absorption, and acoustic streaming. Through in situ imaging we demonstrate quantitatively that these phenomena, acting simultaneously, effectively diminish with increasing build height and size due to acoustic attenuation, consequently decreasing the positive effect of implementing UV-A DED. Thus, this research provides valuable insight into the value of in situ imaging, as well as the effects of UV on DED melt pool dynamics, the stochastic interactions between the melt pool and incoming powder particles, and the limitations of build geometry on the UV-A DED technique.

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Neuroreceptor activation by vibration-assisted tunneling.

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