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Max Zhang

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2 published item(s)

preprint2026arXiv

Continuous quantification of viral plaque dynamics using ultra-large-area label-free imaging enables rapid antiviral susceptibility testing

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.

preprint2026arXiv

Why Do Safety Guardrails Degrade Across Languages?

Large language models exhibit safety degradation in non-English languages. Standard evaluation relies on Jailbreak Success Rate (JSR), which confounds several safety-driving factors into one, obscuring the specific cause(s) of safety failure. We introduce a latent variable model, a Multi-Group Item Response Theory (IRT) framework, that decouples safety-driving factors such as language-agnostic safety robustness ($θ$), intrinsic prompt hardness ($β$), global language processing difficulty ($γ$), and a prompt-specific cross-lingual safety gap ($τ$). Using the MultiJail dataset, we evaluate the safety robustness of 61 model configurations across 5 closed-model families and 10 languages of varying resource, aggregating a dataset of 1.9 million rows. Exploratory Factor Analysis shows safety is primarily unidimensional: models refuse different harm types mainly through a shared mechanism. Contrary to the expected trend that safety degrades largely in low-resource languages, 22 model configurations are more vulnerable in English than in low-resource languages. Low-resource languages produce more uncertain responses (high entropy) than high-resource languages. Also, high-$τ$ prompts cluster in physical harm categories like Theft and Weapons and lower-resource languages, trends validated through cross-dataset generalization. While global translation quality shows low correlation with $τ$, severe mistranslations drive high-bias outliers, as validated by native speakers. Cultural and conceptual grounding mismatches also contribute to $τ$. In predictive validation, the IRT framework achieves $\mathrm{AUC} = 0.940$, outperforming simpler baselines in predicting safe refusal of unsafe prompts. Our framework reveals concept-language vulnerabilities that aggregate metrics obscure, enabling fairer cross-lingual safety evaluation and targeted improvements in dataset construction.