A Humanized CB1R Yeast Biosensor Enables Facile Screening of Cannabinoid Compounds.

Yeast expression of human G-protein-coupled receptors (GPCRs) can be used as a biosensor platform for the detection of pharmaceuticals. Cannabinoid receptor type 1 (CB1R) is of particular interest, given the cornucopia of natural and synthetic cannabinoids being explored as therapeutics. We show for the first time that engineering the N-terminus of CB1R allows for efficient signal transduction in yeast, and that engineering the sterol composition of the yeast membrane modulates its performance.

Radical Stereochemistry: Accounting for Diastereomers in Kinetic Mechanism Development.

Recent work in combustion and atmospheric chemistry has revealed cases in which diastereomers must be distinguished to accurately model a reacting flow. This paper presents an open-source framework for introducing such stereoisomer resolution into a kinetic mechanism. We detail our definitions and algorithms for labeling and enumerating the stereoisomers of a molecule and then generalize our system to describe the transition state (TS) of a reaction.

Quantum and anharmonic effects in non-adiabatic transition state theory.

Quantitative descriptions of non-adiabatic transition rates at intermediate temperatures are challenging due to the simultaneous importance of quantum and anharmonic effects. In this paper, the interplay between quantum effects-for motion across or along the seam of crossing-and anharmonicity in the seam potential is considered within the weak coupling limit. The well-known expression for quantized 1-D motion across the seam (i.

Theoretical Kinetics Predictions for Reactions on the NHO Potential Energy Surface.

Recent modeling studies of ammonia oxidation, which are motivated by the prospective role of ammonia as a zero-carbon fuel, have indicated significant discrepancies among the existing literature mechanisms. In this study, high-level theoretical kinetics predictions have been obtained for reactions on the NHO potential energy surface, including the NH + O, HNO + H, and NH + OH reactions. These reactions have previously been highlighted as important reactions in NH oxidation with high sensitivity and high uncertainty.

A Comparison of Ketamine and Midazolam as First-Line Anesthetic Infusions for Pediatric Status Epilepticus.

Background: Pediatric refractory status epilepticus (RSE) often requires management with anesthetic infusions, but few data compare first-line anesthetics. This study aimed to compare the efficacy and adverse effects of midazolam and ketamine infusions as first-line anesthetics for pediatric RSE.

Methods: Retrospective single-center study of consecutive study participants treated with ketamine or midazolam as the first-line anesthetic infusions for RSE at a quaternary care children's hospital from December 1, 2017, until September 15, 2021.

Bimolecular Peroxy Radical (RO) Reactions and Their Relevance in Radical Initiated Oxidation of Hydrocarbons.

The kinetics of peroxy radical (RO) reactions have been of long-standing interest in atmospheric and combustion chemistry. Nevertheless, the lack of kinetic studies at higher temperatures for their reactions with other radicals such as OH has precluded the inclusion of this class of reactions in detailed kinetics models developed for combustion applications. In this work, guided by the limited room-temperature experimental studies on selected alkyl-peroxy radicals and literature theoretical kinetics on the prototypical CHO + OH system, we have performed parametric studies on the effect of uncertainties in the rate coefficients and branching ratios to potential product channels for RO + OH reactions at higher temperatures.

Quantification of Key Peroxy and Hydroperoxide Intermediates in the Low-Temperature Oxidation of Dimethyl Ether.

Dimethyl ether (DME) oxidation is a model chemical system with a small number of prototypical reaction intermediates that also has practical importance for low-carbon transportation. Although it has been studied experimentally and theoretically, ambiguity remains in the relative importance of competing DME oxidation pathways in the low-temperature autoignition regime. To focus on the primary reactions in DME autoignition, we measured the time-resolved concentration of five intermediates, CHOCHOO (ROO), OOCHOCHOOH (OOQOOH), HOOCHOCHO (hydroperoxymethyl formate, HPMF), CHO, and CHOCHO (methyl formate, MF), from photolytically initiated experiments.

Standardized neonatal continuous infusion concentrations: A quality improvement initiative.

Purpose: Medication errors are a significant and preventable source of patient harm, especially in the neonatal population. Standardized infusion concentrations increase patient safety and streamline the workflow for pharmacists, nurses, and physicians.

Methods: Neonatal continuous infusion concentrations were standardized and implemented into the electronic health record using an automated order panel.

Ketamine for Management of Neonatal and Pediatric Refractory Status Epilepticus.

Background And Objectives: Few data are available regarding the use of anesthetic infusions for refractory status epilepticus (RSE) in children and neonates, and ketamine use is increasing despite limited data. We aimed to describe the impact of ketamine for RSE in children and neonates.

Methods: Retrospective single-center cohort study of consecutive patients admitted to the intensive care units of a quaternary care children's hospital treated with ketamine infusion for RSE.

Functional expression of opioid receptors and other human GPCRs in yeast engineered to produce human sterols.

The yeast Saccharomyces cerevisiae is powerful for studying human G protein-coupled receptors as they can be coupled to its mating pathway. However, some receptors, including the mu opioid receptor, are non-functional, which may be due to the presence of the fungal sterol ergosterol instead of cholesterol. Here we engineer yeast to produce cholesterol and introduce diverse mu, delta, and kappa opioid receptors to create sensitive opioid biosensors that recapitulate agonist binding profiles and antagonist inhibition.

Diastereomers and Low-Temperature Oxidation.

Diastereomers have historically been ignored when building kinetic mechanisms for combustion. Low-temperature oxidation kinetics, which continues to gain interest in both combustion and atmospheric communities, may be affected by the inclusion of diastereomers in radical chain-branching pathways. In this work, key intermediates and transition states lacking stereochemical specification in an existing diethyl ether low-temperature oxidation mechanism were replaced with their diastereomeric counterparts.

The Impacts of Temporal Variation and Individual Differences in Driver Cognitive Workload on ECG-Based Detection.

Objective: This paper aimed to investigate the robustness of driver cognitive workload detection based on electrocardiogram (ECG) when considering temporal variation and individual differences in cognitive workload.

Background: Cognitive workload is a critical component to be monitored for error prevention in human-machine systems. It may fluctuate instantaneously over time even in the same tasks and differ across individuals.

Neurofibromatosis -1 diagnosed from an intraoral swelling - a case series.

The neurofibromatoses [NF 1, NF 2 and schwannomatosis] are a group of genetic disorders that lead to the development of nervous system tumours and have diverse dermatologic, neurologic, ophthalmic, skeletal and vascular effects. The most common is NF 1 (Neurofibromatosis 1) also known as von Recklinghausen's disease, which is one of the most common human genetic diseases. Oral manifestations of NF 1 are reported in 72% of cases and in one of our cases precipitated attendance at a general dental practitioner (GDP), subsequent diagnosis and genetic screening for family members.

A Shock-Tube Study of the Rate Constant of PH + M ⇄ PH + H + M (M = Ar) Using PH Laser Absorption.

Phosphine (PH) is a highly reactive and toxic gas. Prior experimental investigations of PH pyrolysis reactions have included only low-temperature measurements. This study reports the first shock-tube measurements of PH pyrolysis using a new PH laser absorption technique near 4.

Synthetic GPCRs and signal transduction cascades.

G protein-coupled receptors (GPCRs) are a large and diverse group of membrane proteins that constitute over 30% of FDA approved drug targets. Despite their importance, much remains unknown about GPCR signaling at a system's level. Efforts to engineer receptors with orthogonal components have attempted to provide tools to parse signaling and resultant phenotypes.

Using the decision ladder to understand road user decision making at actively controlled rail level crossings.

Rail level crossings (RLXs) represent a key strategic risk for railways worldwide. Despite enforcement and engineering countermeasures, user behaviour at RLXs can often confound expectations and erode safety. Research in this area is limited by a relative absence of insights into actual decision making processes and a focus on only a subset of road user types.

Channel Gating Regulation by the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) First Cytosolic Loop.

In this study, we present data indicating a robust and specific domain interaction between the cystic fibrosis transmembrane conductance regulator (CFTR) first cytosolic loop (CL1) and nucleotide binding domain 1 (NBD1) that allows ion transport to proceed in a regulated fashion. We used co-precipitation and ELISA to establish the molecular contact and showed that binding kinetics were not altered by the common clinical mutation F508del. Both intrinsic ATPase activity and CFTR channel gating were inhibited severely by CL1 peptide, suggesting that NBD1/CL1 binding is a crucial requirement for ATP hydrolysis and channel function.

More than meets the eye: Using cognitive work analysis to identify design requirements for future rail level crossing systems.

An increasing intensity of operations means that the longstanding safety issue of rail level crossings is likely to become worse in the transport systems of the future. It has been suggested that the failure to prevent collisions may be, in part, due to a lack of systems thinking during design, crash analysis, and countermeasure development. This paper presents a systems analysis of current active rail level crossing systems in Victoria, Australia that was undertaken to identify design requirements to improve safety in future rail level crossing environments.

Simulating the dynamic effect of land use and transport policies on the health of populations.

Objectives: We identified the features of a land use-transportation system that optimizes the health and well-being of the population.

Methods: We developed a quantitative system dynamics model to represent relationships among land use, transport, economic development, and population health. Simulation experiments were conducted over a 10-year simulation period to compare the effect of different baseline conditions and land use-transport policies on the number of motor vehicle crash deaths and disability-adjusted life years lost.