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A first-in-class pulsatile FXR agonist for bile-acid-related liver diseases
Abstract Nuclear receptors are central regulators of metabolism1, yet therapeutic strategies that enforce continuous receptor activation frequently lead to reduced efficacy and unacceptable toxicity. Here we report a first-principles drug design strategy that aligns pharmacokinetics with physiological signalling cycles. We developed linafexor, a potent non-bile-acid agonist of the farnesoid X receptor (FXR)2; it is engineered for rapid systemic clearance, which enables pulsatile receptor...
Woman died in hospital 47 days after being kicked by horse
Woman died in hospital 47 days after being kicked by horse Friends say she could have survived if she had been wearing more protection The friend of a “generous and beautiful” mother-of-two says her life may have been saved had she been wearing more protection during a horse accident. Ewa Larsson, 59, was dragged and kicked by a cob called Davy, who she had been leading in Ripple, near Deal, Kent. A jury determined that her cause of death was misadventure.
Whole-genome duplication shaped cell-type evolution in the vertebrate brain
Abstract The complex brains of vertebrates have more cell types than those of their closest relatives. Whole-genome duplications (WGDs) occurred during early vertebrate evolution1, but it is unclear whether the duplicated genes (ohnologues) facilitated cell-type evolution. Here using brain single-cell transcriptomes from five chordates—human2, mouse3, lizard4, lamprey5 and amphioxus—we report that many cell-type families with conserved core transcription factors in vertebrates do not show...
A Lecture Note on Offline RL and IRL, Part II: Foundations of Inverse Reinforcement Learning and Dynamic Discrete Choice Models
arXiv:2605.30843v1 Announce Type: new Abstract: In the forward reinforcement-learning problem, the reward is fixed and known; the learner is asked to find a good policy or value function. Here we turn the question around. Given offline data generated by an expert, can we recover the reward the expert was optimizing?
Council says 'it's allowed' as traffic warden parks on double yellow lines
Council says 'it's allowed' as traffic warden parks on double yellow lines A driving instructor was “outraged” to see a parking warden leave their van on double yellow lines - but the local council insists it was all above board. John Allison took a picture of the scene outside his home in Russell Street, Dover, where a double yellow line is in place as otherwise emergency vehicles are obstructed from getting past. “Do they give themselves a ticket?”