Activation of tetrodotoxin-resistant sodium channels contributes to action potential electrogenesis in neurons. Antisense oligonucleotide studies directed against Nav1.8 have shown that this channel contributes to experimental inflammatory and neuropathic pain. We report here the discovery of A-803467, a sodium channel blocker that potently blocks tetrodotoxin-resistant currents (IC50 ؍ 140 nM) and the generation of spontaneous and electrically evoked action potentials in vitro in rat dorsal root ganglion neurons. In recombinant cell lines, A-803467 potently blocked human Nav1.8 (IC50 ؍ 8 nM) and was >100-fold selective vs. human Nav1.2, Nav1.3, Nav1.5, and Nav1.
Language modelling provides a step towards intelligent communication systems by harnessing large repositories of written human knowledge to better predict and understand the world. In this paper, we present an analysis of Transformer-based language model performance across a wide range of model scales -from models with tens of millions of parameters up to a 280 billion parameter model called Gopher. These models are evaluated on 152 diverse tasks, achieving state-of-the-art performance across the majority. Gains from scale are largest in areas such as reading comprehension, fact-checking, and the identification of toxic language, but logical and mathematical reasoning see less benefit. We provide a holistic analysis of the training dataset and model's behaviour, covering the intersection of model scale with bias and toxicity. Finally we discuss the application of language models to AI safety and the mitigation of downstream harms.
Controversy surrounds occupational health and safety regulators, with some observers claiming that workplace regulations damage firms' competitiveness and destroy jobs and others arguing that they make workplaces safer at little cost to employers and employees. We analyzed a natural field experiment to examine how workplace safety inspections affected injury rates and other outcomes. We compared 409 randomly inspected establishments in California with 409 matched-control establishments that were eligible, but not chosen, for inspection. Compared with controls, randomly inspected employers experienced a 9.4% decline in injury rates (95% confidence interval = -0.177 to -0.021) and a 26% reduction in injury cost (95% confidence interval = -0.513 to -0.083). We find no evidence that these improvements came at the expense of employment, sales, credit ratings, or firm survival.
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