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A programmable linear resistor with a compact footprint would have profound implications for microelectronics, enabling efficient in-sensor analog signal processing and in-memory computing. Non-volatile memory offers a potential solution but suffers from limitations due to the programming mechanisms that confine switching to nanoscale constrictions or field-sensitive semiconductor junctions, leading to non-linear current-voltage relationships and errors. Here, we introduce a tunable resistor that is programmed into non-volatile, high-precision resistance states spanning nine orders of magnitude, with linear current-voltage characteristics across the entire range -- significantly improving the performance and widening the application space of resistive memory. A key advance is an electrothermal gate that simultaneously spreads heat and electrochemical reactions during programming to enable large, bulk composition modulation. The volumetric modulation can host thousands of linear resistance states with 100x lower conductance errors than other memory. This enables direct processing of analog signals with high fidelity, and we demonstrate variable-gain amplification, division, and multiplication. Integration with CMOS is used to show resilience to electrical and thermal disturb in arrays and to demonstrate retention of analog levels at <1% average loss for more than 2 months across 100 devices. Simulations indicate matrix multiplication efficiency could approach >1,000 TOPS/W.

Identifying small molecules that inhibit protein synthesis by selectively stalling the ribosome constitutes a new strategy for therapeutic development. Compounds that inhibit the translation of PCSK9, a major regulator of low-density lipoprotein cholesterol, have been identified that reduce LDL cholesterol in preclinical models and that affect the translation of only a few off-target proteins. Although some of these compounds hold potential for future therapeutic development, it is not known how they impact the physiology of cells or ribosome quality control pathways. Here we used a genome-wide CRISPRi screen to identify proteins and pathways that modulate cell growth in the presence of high doses of a selective PCSK9 translational inhibitor, PF-06378503 (PF8503). The two most potent genetic modifiers of cell fitness in the presence of PF8503, the ubiquitin binding protein ASCC2 and helicase ASCC3, bind to the ribosome and protect cells from toxic effects of high concentrations of the compound. Surprisingly, translation quality control proteins Pelota (PELO) and HBS1L sensitize cells to PF8503 treatment. In genetic interaction experiments, ASCC3 acts together with ASCC2, and functions downstream of HBS1L. Taken together, these results identify new connections between ribosome quality control pathways, and provide new insights into the selectivity of compounds that stall human translation that will aid the development of next-generation selective translation stalling compounds to treat disease.