Towards Shutdownable Agents via Stochastic Choice

Some worry that advanced artificial agents may resist being shut down. The Incomplete Preferences Proposal (IPP) is an idea for ensuring that doesn't happen. A key part of the IPP is using a novel 'Discounted REward for Same-Length Trajectories (DREST)' reward function to train agents to (1) pursue goals effectively conditional on each trajectory-length (be 'USEFUL'), and (2) choose stochastically between different trajectory-lengths (be 'NEUTRAL' about trajectory-lengths). In this paper, we propose evaluation metrics for USEFULNESS and NEUTRALITY. We use a DREST reward function to train simple agents to navigate gridworlds, and we find that these agents learn to be USEFUL and NEUTRAL. Our results thus suggest that DREST reward functions could also train advanced agents to be USEFUL and NEUTRAL, and thereby make these advanced agents useful and shutdownable

Radioactive heat production of six geologically important nuclides

Heat production rates for the geologically important nuclides ${}^{26}$Al, ${}^{40}$K, ${}^{60}$Fe, ${}^{232}$Th, ${}^{235}$U, and ${}^{238}$U are calculated on the basis of recent data on atomic and nuclear properties. The revised data differ by several per cent from some older values, but indicate that more recent analyses converge toward values with an accuracy sufficient for all common geoscience applications, although some possibilities for improvement still remain, especially in the case of ${}^{40}$K and with regard to the determination of half-lives. A Python script is provided for calculating heat production (https://github.com/trg818/radheat).Comment: 14 pages, 1 figur

Serine Protease Autotransporters of Enterobacteriaceae (SPATEs): Biogenesis and Function

Serine Protease Autotransporters of Enterobacteriaceae (SPATEs) constitute a large family of proteases secreted by Escherichia coli and Shigella. SPATEs exhibit two distinct proteolytic activities. First, a C-terminal catalytic site triggers an intra-molecular cleavage that releases the N-terminal portion of these proteins in the extracellular medium. Second, the secreted N-terminal domains of SPATEs are themselves proteases; each contains a canonical serine-protease catalytic site. Some of these secreted proteases are toxins, eliciting various effects on mammalian cells. Here, we discuss the biogenesis of SPATEs and their function as toxins

Cardiomyocytes from human pluripotent stem cells: from laboratory curiosity to industrial biomedical platform

Cardiomyocytes from human pluripotent stem cells (hPSCs-CMs) could revolutionise biomedicine. Global burden of heart failure will soon reach USD $90bn, while unexpected cardiotoxicity underlies 28% of drug withdrawals. Advances in hPSC isolation, Cas9/CRISPR genome engineering and hPSC-CM differentiation have improved patient care, progressed drugs to clinic and opened a new era in safety pharmacology. Nevertheless, predictive cardiotoxicity using hPSC-CMs contrasts from failure to almost total success. Since this likely relates to cell immaturity, efforts are underway to use biochemical and biophysical cues to improve many of the ~ 30 structural and functional properties of hPSC-CMs towards those seen in adult CMs. Other developments needed for widespread hPSC-CM utility include subtype specification, cost reduction of large scale differentiation and elimination of the phenotyping bottleneck. This review will consider these factors in the evolution of hPSC-CM technologies, as well as their integration into high content industrial platforms that assess structure, mitochondrial function, electrophysiology, calcium transients and contractility. This article is part of a Special Issue entitled: Cardiomyocyte Biology: Integration of Developmental and Environmental Cues in the Heart edited by Marcus Schaub and Hughes Abriel