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Sparse matrix-matrix multiplication (SpMM) is a critical computational kernel in numerous scientific and machine learning applications. SpMM involves massive irregular memory accesses and poses great challenges to conventional cache-based computer architectures. Recently dedicated SpMM accelerators have been proposed to enhance SpMM performance. However, current SpMM accelerators still face challenges in adapting to varied sparse patterns, fully exploiting inherent parallelism, and optimizing cache performance. To address these issues, we introduce ACES, a novel SpMM accelerator in this study. First, ACES features an adaptive execution flow that dynamically adjusts to diverse sparse patterns. The adaptive execution flow balances parallel computing efficiency and data reuse. Second, ACES incorporates locality-concurrency co-optimizations within the global cache. ACES utilizes a concurrency-aware cache management policy, which considers data locality and concurrency for optimal replacement decisions. Additionally, the integration of a non-blocking buffer with the global cache enhances concurrency and reduces computational stalls. Third, the hardware architecture of ACES is designed to integrate all innovations. The architecture ensures efficient support across the adaptive execution flow, advanced cache optimizations, and fine-grained parallel processing. Our performance evaluation demonstrates that ACES significantly outperforms existing solutions, providing a 2.1× speedup and marking a substantial advancement in SpMM acceleration. 

Abstract Bispecific antibodies (BsAbs) represent an emerging class of immunotherapy, but inefficiency in the current discovery has limited their broad clinical availability. Here we report a high throughput, agnostic, single-cell-based functional screening pipeline, comprising molecular and cell engineering for efficient generation of BsAb library cells, followed by functional interrogation at the single-cell level to identify and sort positive clones and downstream sequence identification and functionality characterization. Using a CD19xCD3 bispecific T cell engager (BiTE) as a model, we demonstrate that our single-cell platform possesses a high throughput screening efficiency of up to one and a half million variant library cells per run and can isolate rare functional clones at a low abundance of 0.008%. Using a complex CD19xCD3 BiTE-expressing cell library with approximately 22,300 unique variants comprising combinatorially varied scFvs, connecting linkers and VL/VH orientations, we have identified 98 unique clones, including extremely rare ones (~ 0.001% abundance). We also discovered BiTEs that exhibit novel properties and insights to design variable preferences for functionality. We expect our single-cell platform to not only increase the discovery efficiency of new immunotherapeutics, but also enable identifying generalizable design principles based on an in-depth understanding of the inter-relationships between sequence, structure, and function.