arXiv:2602.18472v1 Announce Type: cross Abstract: Physiologically Based Pharmacokinetic (PBPK) modeling is a cornerstone of model-informed drug development (MIDD), providing a mechanistic framework to predict drug absorption, distribution, metabolism, and excretion (ADME). Despite its utility, adoption is hindered by high computational costs for large-scale simulations, difficulty in parameter identification for complex biological systems, and uncertainty in interspecies extrapolation. In this work, we propose a unified Scientific Machine Learning (SciML) framework that bridges mechanistic rigor and data-driven flexibility. We introduce three contributions: (1) Foundation PBPK Transformers, which treat pharmacokinetic forecasting as a sequence modeling task; (2) Physiologically Constrained Diffusion Models (PCDM), a generative approach that uses a physics-informed loss to synthesize biologically compliant virtual patient populations; and (3) Neural Allometry, a hybrid architecture combining Graph Neural Networks (GNNs) with Neural ODEs to learn continuous cross-species scaling laws. Experiments on synthetic datasets show that the framework reduces physiological violation rates from 2.00% to 0.50% under constraints while offering a path to faster simulation.

arXiv:2505.16670v4 Announce Type: replace-cross Abstract: Large language models (LLMs) are widely deployed, but their substantial compute demands make them vulnerable to inference cost attacks that aim to deliberately maximize the output length. In this work, we investigate a distinct attack surface: maximizing inference cost by tampering with the model parameters instead of inputs. This approach leverages the established capability of Bit-Flip Attacks (BFAs) to persistently alter model behavior via minute weight perturbations, effectively decoupling the attack from specific input queries. To realize this, we propose BitHydra, a framework that addresses the unique optimization challenge of identifying the exact weight bits that maximize generation cost. We formulate the attack as a constrained Binary Integer Programming (BIP) problem designed to systematically suppress the end-of-sequence (i.e., ) probability. To overcome the intractability of the discrete search space, we relax the problem into a continuous optimization task and solve it via the Alternating Direction Method of Multipliers (ADMM). We evaluate BitHydra across 10 LLMs (1.5B-16B). Our results demonstrate that the proposed optimization method efficiently achieves endless generation with as few as 1-4 bit flips on all testing models, verifying the effectiveness of the ADMM-based formulation against both standard models and potential defenses.