1.4APP-PHMay 3
Continuous quantification of viral plaque dynamics using ultra-large-area label-free imaging enables rapid antiviral susceptibility testingMerve Eryilmaz, Yuzhu Li, Xiao Wang et al.
The plaque reduction assay (PRA) remains the gold standard for antiviral susceptibility testing, evaluating drug potency by measuring reductions in plaque-forming units (PFUs). However, the traditional PRA is time-consuming, labor-intensive, prone to manual counting errors, and offers limited scalability. Moreover, its reliance on destructive fixation and chemical staining reduces the assay to a static, endpoint observation, obscuring the dynamic, time-resolved kinetics of dose-dependent viral inhibition. Here, we introduce a label-free, time-resolved PRA platform that transforms the conventional assay into a continuous, high-dimensional measurement of viral infection dynamics. Our system integrates a compact lens-free imaging setup with a custom-designed ultra-large-area (100 cm^2) thin-film transistor (TFT) image sensor and deep learning-based algorithms to autonomously quantify PFU dynamics within an incubator. Validated using herpes simplex virus type-1 (HSV-1) treated with acyclovir, the platform matched chemically-stained ground truth measurements with zero false positives while accelerating readout by ~26 hours. Crucially, our system revealed that increasing drug concentrations induce temporally distinct delays and suppress new PFU formation, enabling conclusive drug efficacy evaluations within ~60 hours post-infection. This scalable, label-free framework redefines antiviral susceptibility testing as a rapid, time-resolved and information-rich measurement framework, providing a generalizable platform for virology research, high-throughput drug screening, and clinical diagnostics.
14.7LGJun 19
Demystifying Numerical Instability in LLM Inference: Achieving Reproducible Inference for Mission-Critical Tasks with HEALZhenting Zhu, Lucas Thai, Shan Yu et al.
As Large Language Models (LLMs) deploy into mission-critical domains (e.g., finance, medicine, and law), output reproducibility has become a strict system requirement. While practitioners use greedy decoding to eliminate algorithmic stochasticity, empirical deployments with 16-bit precisions still exhibit catastrophic output divergence across heterogeneous GPUs. Through SASS-level profiling, we reveal that this inconsistency is fundamentally driven by truncation errors introduced during downcasting at kernel boundaries. However, achieving reproducibility via a global FP32 pipeline incurs prohibitive system penalties: bypassing 16-bit hardware accelerators hurts compute efficiency, while upcasting the KV cache doubles memory overhead. To bridge this gap, we propose Hybrid Error ALleviation (HEAL), a targeted intervention that approximates FP32 precision while resolving hardware constraints through two targeted mechanisms. First, recognizing that floating-point formats underutilize their bit-width for Q, K, V tensors, HEAL applies INT16 quantization that preserves numerical stability without expanding the KV cache footprint. Second, HEAL synthesizes high-precision matrix multiplications via an algebraic error compensation strategy, executing entirely on high-throughput 16-bit Tensor Cores. To evaluate our approach practically, we introduce MCR-Bench, a benchmark targeting reproducibility in mission-critical tasks. HEAL achieves the same level of reproducibility on downstream tasks as the FP32 baseline while reducing the performance overhead by up to 7.1x.