Phase resetting and its implications for interval timing with intruders

AbstractTime perception in the second-to-minutes range is crucial for fundamental cognitive processes like decision making, rate calculation, and planning. We used a striatal beat frequency (SBF) computational model to predict the response of an interval timing network to intruders, such as gaps in conditioning stimulus (CS), or distracters presented during the uninterrupted CS. We found that, depending on the strength of the input provided to neural oscillators by the intruder, the SBF model can either ignore it or reset timing. The significant delays in timing produced by emotionally charged distracters were numerically simulated by a strong phase resetting of all neural oscillators involved in the SBF network for the entire duration of the evoked response. The combined effect of emotional distracter and pharmacological manipulations was modeled in our SBF model by modulating the firing frequencies of neural oscillators after they are released from inhibition due to emotional distracters.This article is part of a Special Issue entitled: SI: Associative and Temporal Learning

Expedited Mapping of the Ligandable Proteome Using Fully Functionalized Enantiomeric Probe Pairs

A fundamental challenge in chemical biology and medicine is to understand and expand the fraction of the human proteome that can be targeted by small molecules. We recently described a strategy that integrates fragment-based ligand discovery with chemical proteomics to furnish global portraits of reversible small molecule-protein interactions in human cells.Excavating clear structure-activity relationships from these “ligandability” maps, however, was confounded by the distinct physicochemical properties and corresponding overall protein-binding potential of individual fragments. Here, we describe a compelling solution to this problem by introducing a next-generation set of fully functionalized fragments (FFFs) differing only in absolute stereochemistry. Using these enantiomeric probe pairs, or “enantioprobes”, we identify numerous stereoselective protein-fragment interactions in cells and show that these interactions occur at functional sites on proteins from diverse classes. Our findings thus indicate that incorporating chirality into FFF libraries provides a robust and streamlined method to discover ligandable proteins in cells.</div

Sources of Formaldehyde in U.S. Oil and Gas Production Regions

We analyzed observational and model data to study the sources of formaldehyde over oil and gas production regions and to investigate how these observations may be used to constrain oil and gas volatile organic compound (VOC) emissions. The analysis of aircraft and satellite data consistently found that formaldehyde over oil and gas production regions during spring and summer is mostly formed by the photooxidation of precursor VOCs. Formaldehyde columns over the Permian Basin, one of the largest oil- and gas-producing regions in the United States, are correlated with the production locations. Formaldehyde simulations by the atmospheric chemistry and transport model WRF-Chem, which included oil and gas NOx and VOC emissions from the fuel-based oil and gas inventory, were in very good agreement with TROPOMI satellite measurements. Sensitivity studies illustrated that VOCs released from oil and gas activities are important precursors to formaldehyde, but other sources of VOCs contribute as well and that the formation of secondary formaldehyde is highly sensitive to NOx. We also investigated the ability of the chemical mechanism used in WRF-Chem to represent formaldehyde formation from oil and gas hydrocarbons by comparing against the Master Chemical Mechanism. Further, our work provides estimates of primary formaldehyde emissions from oil and gas production activities, with per basin averages ranging from 0.07 to 2.2 kg h-1 in 2018. A separate estimate for natural gas flaring found that flaring emissions could contribute 5 to 12% to the total primary formaldehyde emissions for the Permian Basin in 2018.Green Open Access added to TU Delft Institutional Repository ‘You share, we take care!’ – Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.Control & SimulationAtmospheric Remote Sensin