We present in this work a new calculation of the standard-model benchmark value for the effective number of neutrinos, Neff SM, that quantifies the cosmological neutrino-to-photon energy densities. The calculation takes into account neutrino flavour oscillations, finite-temperature effects in the quantum electrodynamics plasma to O(e3), where e is the elementary electric charge, and a full evaluation of the neutrino-neutrino collision integral. We provide furthermore a detailed assessment of the uncertainties in the benchmark Neff SM value, through testing the value's dependence on (i) optional approximate modelling of the weak collision integrals, (ii) measurement errors in the physical parameters of the weak sector, and (iii) numerical convergence, particularly in relation to momentum discretisation. Our new, recommended standard-model benchmark is Neff SM 3.0440 ±0.0002, where the nominal uncertainty is attributed predominantly to errors incurred in the numerical solution procedure (|δ Neff| ∼10-4), augmented by measurement errors in the solar mixing angle sin2θ 12 (|δ Neff| ∼10-4).

We revisit and quantify in this work several aspects of Standard Model physics at finite temperature that drive the theoretical value of the cosmological parameter, the effective number of neutrinos Neff, away from 3 in the early universe. Our chief focus is finite-temperature corrections to the equation of state of the QED plasma in the vicinity of neutrino decoupling at T ∼ 1 MeV, where T is the photon temperature. Working in the instantaneous decoupling approximation, we recover at 𝒪(e2), where e is the elementary electric charge, the well-established correction of δ Neff(2) ≃ 0.010 across a range of plausible neutrino decoupling temperatures, in contrast to an erroneous claim in the recent literature which found twice as large an effect. At 𝒪(e3) we find a new and significant correction of δ Neff(3) ≃ −0.001 that has so far not been accounted for in any precision neutrino decoupling calculation of Neff, significant because this correction is in fact larger than—or at least comparable to—the change in Neff induced between including and excluding neutrino oscillations in the transport modelling. In addition to the QED equation of state, we make a first pass at quantifying finite-temperature QED corrections to the weak interaction rates that directly affect the neutrino decoupling process, and find in this connection that the 𝒪(e2) thermal electron mass correction induces a change of δ Neffmth ≲ 10−4. A complete assessment of the various effects considered in this work on the final value of Neff will necessitate an account of neutrino energy transport beyond the instantaneous decoupling approximation. However, relative to Neff = 3.044 obtained in the most recent such calculation, we expect the new effects found in this work to lower the number to Neff = 3.043.

Small molecule drug discovery has been propelled by the continual development of novel scientific methodologies to occasion therapeutic advances. Although established biophysical methods can be used to obtain information regarding the molecular mechanisms underlying drug action, these approaches are often inefficient, low throughput, and ineffective in the analysis of heterogeneous systems including dynamic oligomeric assemblies and proteins that have undergone extensive post-translational modification. Native mass spectrometry can be used to probe protein–small molecule interactions with unprecedented speed and sensitivity, providing unique insights into polydisperse biomolecular systems that are commonly encountered during the drug discovery process. In this review, we describe potential and proven applications of native MS in the study of interactions between small, drug-like molecules and proteins, including large multiprotein complexes and membrane proteins. Approaches to quantify the thermodynamic and kinetic properties of ligand binding are discussed, alongside a summary of gas-phase ion activation techniques that have been used to interrogate the structure of protein–small molecule complexes. We additionally highlight some of the key areas in modern drug design for which native mass spectrometry has elicited significant advances. Future developments and applications of native mass spectrometry in drug discovery workflows are identified, including potential pathways toward studying protein–small molecule interactions on a whole-proteome scale.

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The structural diversity of natural products offers unique opportunities for drug discovery, but challenges associated with their isolation and screening can hinder the identification of drug-like molecules from complex natural product extracts. Here we introduce a mass spectrometry-based approach that integrates untargeted metabolomics with multistage, high-resolution native mass spectrometry to rapidly identify natural products that bind to therapeutically relevant protein targets. By directly screening crude natural product extracts containing thousands of drug-like small molecules using a single, rapid measurement, novel natural product ligands of human drug targets could be identified without fractionation. This method should significantly increase the efficiency of target-based natural product drug discovery workflows.