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Zeroth-order fine-tuning eliminates explicit back-propagation and reduces memory overhead for large language models (LLMs), making it a promising approach for on-device fine-tuning tasks. However, existing memory-centric accelerators fail to fully leverage these benefits due to inefficiencies in balancing bit density, compute-in-memory capability, and endurance-retention trade-off. We present a reliability-aware, analog multi-level-cell (MLC) eDRAM-RRAM compute-in-memory (CIM) solution co-designed with zeroth-order optimization for language model fine-tuning. An RRAM-assisted eDRAM MLC programming scheme is developed, along with a process-voltage-temperature (PVT)-robust, large-sensing-window time-to-digital converter (TDC). The MLC-eDRAM integrating two-finger MOM provides 12× improvement in bit density over state-of-the-art MLC design. Another 5× density and 2× retention benefits are gained by adopting BEOL In2O3 FETs. 

Abstract The discovery of two-dimensional (2D) ferromagnets and antiferromagnets with topologically nontrivial electronic band structures makes the study of the Nernst effect in 2D materials of great importance and interest. To measure the Nernst coefficient of 2D materials, the detection of the temperature gradient is crucial. Although the micro-fabricated metal wires provide a simple but accurate way for temperature detection, a linear-response assumption that the temperature gradient is a constant is still necessary and has been widely used to evaluate the temperature gradient. However, with the existence of substrates, this assumption cannot be precise. In this study, we clearly show that the temperature gradient strongly depends on the distance from the heater by both thermoelectric transport and thermoreflectance measurements. Fortunately, both measurements show that the temperature gradient can be well described by a linear function of the distance from the heater. This linearity is further confirmed by comparing the measured Nernst coefficient to the value calculated from the generalized Mott’s formula. Our results demonstrate a precise way to measure the Nernst coefficient of 2D materials and would be helpful for future studies. 

Abstract Candidate bacterial phylum Omnitrophota has not been isolated and is poorly understood. We analysed 72 newly sequenced and 349 existing Omnitrophota genomes representing 6 classes and 276 species, along with Earth Microbiome Project data to evaluate habitat, metabolic traits and lifestyles. We applied fluorescence-activated cell sorting and differential size filtration, and showed that most Omnitrophota are ultra-small (~0.2 μm) cells that are found in water, sediments and soils. Omnitrophota genomes in 6 classes are reduced, but maintain major biosynthetic and energy conservation pathways, including acetogenesis (with or without the Wood-Ljungdahl pathway) and diverse respirations. At least 64% of Omnitrophota genomes encode gene clusters typical of bacterial symbionts, suggesting host-associated lifestyles. We repurposed quantitative stable-isotope probing data from soils dominated by andesite, basalt or granite weathering and identified 3 families with high isotope uptake consistent with obligate bacterial predators. We propose that most Omnitrophota inhabit various ecosystems as predators or parasites. 

This book constitutes the refereed proceedings of the 27th Annual International Conference on Research in Computational Molecular Biology, RECOMB 2023, held in Istanbul, Turkey, from April 16–19, 2023. The 11 regular and 33 short papers presented in this book were carefully reviewed and selected from 188 submissions. The papers report on original research in all areas of computational molecular biology and bioinformatics. 

Abstract Trace metals have been an important ingredient for life throughout Earth’s history. Here, we describe the genome-guided cultivation of a member of the elusive archaeal lineage Caldarchaeales (syn. Aigarchaeota ), Wolframiiraptor gerlachensis , and its growth dependence on tungsten. A metagenome-assembled genome (MAG) of W. gerlachensis encodes putative tungsten membrane transport systems, as well as pathways for anaerobic oxidation of sugars probably mediated by tungsten-dependent ferredoxin oxidoreductases that are expressed during growth. Catalyzed reporter deposition-fluorescence in-situ hybridization (CARD-FISH) and nanoscale secondary ion mass spectrometry (nanoSIMS) show that W. gerlachensis preferentially assimilates xylose. Phylogenetic analyses of 78 high-quality Wolframiiraptoraceae MAGs from terrestrial and marine hydrothermal systems suggest that tungsten-associated enzymes were present in the last common ancestor of extant Wolframiiraptoraceae . Our observations imply a crucial role for tungsten-dependent metabolism in the origin and evolution of this lineage, and hint at a relic metabolic dependence on this trace metal in early anaerobic thermophiles. 

Abstract Although the phylum Chloroflexota is ubiquitous, its biology and evolution are poorly understood due to limited cultivability. Here, we isolated two motile, thermophilic bacteria from hot spring sediments belonging to the genus Tepidiforma and class Dehalococcoidia within the phylum Chloroflexota. A combination of cryo-electron tomography, exometabolomics, and cultivation experiments using stable isotopes of carbon revealed three unusual traits: flagellar motility, a peptidoglycan-containing cell envelope, and heterotrophic activity on aromatics and plant-associated compounds. Outside of this genus, flagellar motility has not been observed in Chloroflexota, and peptidoglycan-containing cell envelopes have not been described in Dehalococcoidia. Although these traits are unusual among cultivated Chloroflexota and Dehalococcoidia, ancestral character state reconstructions showed flagellar motility and peptidoglycan-containing cell envelopes were ancestral within the Dehalococcoidia, and subsequently lost prior to a major adaptive radiation of Dehalococcoidia into marine environments. However, despite the predominantly vertical evolutionary histories of flagellar motility and peptidoglycan biosynthesis, the evolution of enzymes for degradation of aromatics and plant-associated compounds was predominantly horizontal and complex. Together, the presence of these unusual traits in Dehalococcoidia and their evolutionary histories raise new questions about the timing and selective forces driving their successful niche expansion into global oceans.