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Subcellular pharmacokinetic measurements have informed the study of central nervous system (CNS)–acting drug mechanisms. Recent investigations have been enhanced by the use of genetically encoded fluorescent biosensors for drugs of interest at the plasma membrane and in organelles. We describe screening and validation protocols for identifying hit pairs comprising a drug and biosensor, with each screen including 13–18 candidate biosensors and 44–84 candidate drugs. After a favorable hit pair is identified and validated via these protocols, the biosensor is then optimized, as described in other papers, for sensitivity and selectivity to the drug. We also show sample hit pair data that may lead to future intensity-based drug-sensing fluorescent reporters (iDrugSnFRs). These protocols will assist scientists to use fluorescence responses as criteria in identifying favorable fluorescent biosensor variants for CNS-acting drugs that presently have no corresponding biosensor partner. Graphical abstract:

Abstract In this article, we highlight the alterations in the photoinduced electron transfer (ET) and hydrogen atom transfer (HAT) pathways between an anti-tumor drug vitamin-K3 (MQ) and a nucleobase adenine (ADN) in the presence of gold (Au) and iron (Fe) nanoparticles (NPs). Inside the confined micellar media, with laser flash photolysis corroborated with an external magnetic field (MF), we have detected the transient geminate radicals of MQ and ADN, photo-generated through ET and HAT. We observe that the presence of AuNP on the MQ-ADN complex (AuMQ-ADN) assists HAT by limiting the ET channel, on the other hand, FeNP on the MQ-ADN complex (FeMQ-ADN) mostly favors a facile PET. We hypothesize that through selective interactions of the ADN molecules with AuNP and MQ molecules with FeNP, a preferential HAT and PET process is eased. The enhanced HAT and PET have been confirmed by the escape yields of radical intermediates by time-resolved transient absorption spectroscopy in the presence of MF.

The target for the “rapid” (100-fold selectivity over other ligands tested, including R-ketamine. We targeted each of the sensors to either the plasma membrane (PM) or the endoplasmic reticulum (ER). Measurements on these biosensors expressed in Neuro2a cells and in human dopaminergic neurons differentiated from induced pluripotent stem cells (iPSCs) show that S-ketamine enters the ER within a few seconds after appearing in the external solution near the PM, then leaves as rapidly after S-ketamine is removed from the extracellular solution. In cells, S-slopes for the ER and PM-targeted sensors differ by

Chemically reactive plasmas operating in the 1 mTorr–10 Torr pressure range are widely used for thin film processing in the semiconductor industry. Plasma modeling has come to play an important role in the design of these plasma processing systems. A number of 3-dimensional (3D) fluid and hybrid plasma modeling examples are used to illustrate the role of computational investigations in design of plasma processing hardware for applications such as ion implantation, deposition, and etching. A model for a rectangular inductively coupled plasma (ICP) source is described, which is employed as an ion source for ion implantation. It is shown that gas pressure strongly influences ion flux uniformity, which is determined by the balance between the location of plasma production and diffusion. The effect of chamber dimensions on plasma uniformity in a rectangular capacitively coupled plasma (CCP) is examined using an electromagnetic plasma model. Due to high pressure and small gap in this system, plasma uniformity is found to be primarily determined by the electric field profile in the sheath/pre-sheath region. A 3D model is utilized to investigate the confinement properties of a mesh in a cylindrical CCP. Results highlight the role of hole topology and size on the formation of localized hot-spots. A 3D electromagnetic plasma model for a cylindrical ICP is used to study inductive versus capacitive power coupling and how placement of ground return wires influences it. Finally, a 3D hybrid plasma model for an electron beam generated magnetized plasma is used to understand the role of reactor geometry on plasma uniformity in the presence of E  ×  B drift. [ABSTRACT FROM AUTHOR]

A two-dimensional plasma model that includes the full set of Maxwell equations is used to understand the physics of very high frequency capacitively coupled plasmas. The effect of radio frequency (RF) source power, inter-electrode gap and gas mixture (Ar, Ar/SF6, Ar/CF4) on the plasma characteristics is investigated. The computational results show that the plasma spatial profile is influenced by both electrostatic and electromagnetic effects. The electrostatic power deposition is stronger at the electrode edges due to electric field enhancement at corners. Therefore, when the electrostatic effects are dominant, the plasma density peaks off-axis. Due to a standing electromagnetic wave in the chamber, the electron density peak moves to the chamber center under conditions where electromagnetic effects become strong. Inductive heating due to the radial electromagnetic electric field can also influence the plasma spatial profile. The relative importance of electromagnetic and electrostatic effects is found to be a function of the RF source power, the inter-electrode gap and the plasma electronegativity. While the electron density peaks on-axis at a low source power, inductive power deposition at higher source powers shifts the electron density peak towards the electrode edge. Electrostatic power deposition makes the plasma more uniform at smaller inter-electrode gaps. Due to a lower electron density and a larger applied RF potential, electrostatic effects become more dominant in electronegative discharges. [ABSTRACT FROM AUTHOR]