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Optimizing doses for multiple indications is challenging. The pooled approach of finding a single optimal biological dose (OBD) for all indications ignores that dose-response or dose-toxicity curves may differ between indications, resulting in varying OBDs. Conversely, indication-specific dose optimization often requires a large sample size. To address this challenge, we propose a Randomized two-stage basket trial design that Optimizes doses in Multiple Indications (ROMI). In stage 1, for each indication, response and toxicity are evaluated for a high dose, which may be a previously obtained MTD, with a rule that stops accrual to indications where the high dose is unsafe or ineffective. Indications not terminated proceed to stage 2, where patients are randomized between the high dose and a specified lower dose. A latent-cluster Bayesian hierarchical model is employed to borrow information between indications, while considering the potential heterogeneity of OBD across indications. Indication-specific utilities are used to quantify response-toxicity trade-offs. At the end of stage 2, for each indication with at least one acceptable dose, the dose with highest posterior mean utility is selected as optimal. Two versions of ROMI are presented, one using only stage 2 data for dose optimization and the other optimizing doses using data from both stages. Simulations show that both versions have desirable operating characteristics compared to designs that either ignore indications or optimize dose independently for each indication.

Large language models (LLMs) such as ChatGPT and Vicuna have shown remarkable capacities in comprehending and producing language. However, their internal workings remain a black box, and it is unclear whether LLMs and chatbots can develop humanlike characteristics in language use. Cognitive scientists have devised many experiments that probe, and have made great progress in explaining, how people comprehend and produce language. We subjected ChatGPT and Vicuna to 12 of these experiments ranging from sounds to dialogue, preregistered and with 1000 runs (i.e., iterations) per experiment. ChatGPT and Vicuna replicated the human pattern of language use in 10 and 7 out of the 12 experiments, respectively. The models associated unfamiliar words with different meanings depending on their forms, continued to access recently encountered meanings of ambiguous words, reused recent sentence structures, attributed causality as a function of verb semantics, and accessed different meanings and retrieved different words depending on an interlocutor's identity. In addition, ChatGPT, but not Vicuna, nonliterally interpreted implausible sentences that were likely to have been corrupted by noise, drew reasonable inferences, and overlooked semantic fallacies in a sentence. Finally, unlike humans, neither model preferred using shorter words to convey less informative content, nor did they use context to resolve syntactic ambiguities. We discuss how these convergences and divergences may result from the transformer architecture. Overall, these experiments demonstrate that LLMs such as ChatGPT (and Vicuna to a lesser extent) are humanlike in many aspects of human language processing.

Can we use spiking neural networks (SNN) as generative models of multi-neuronal recordings, while taking into account that most neurons are unobserved? Modeling the unobserved neurons with large pools of hidden spiking neurons leads to severely underconstrained problems that are hard to tackle with maximum likelihood estimation. In this work, we use coarse-graining and mean-field approximations to derive a bottom-up, neuronally-grounded latent variable model (neuLVM), where the activity of the unobserved neurons is reduced to a low-dimensional mesoscopic description. In contrast to previous latent variable models, neuLVM can be explicitly mapped to a recurrent, multi-population SNN, giving it a transparent biological interpretation. We show, on synthetic spike trains, that a few observed neurons are sufficient for neuLVM to perform efficient model inversion of large SNNs, in the sense that it can recover connectivity parameters, infer single-trial latent population activity, reproduce ongoing metastable dynamics, and generalize when subjected to perturbations mimicking photo-stimulation., Comment: 23 pages, 7 figures

Electromigration (EM) is one of the major concerns in the reliability analysis of very large scale integration (VLSI) systems due to the continuous technology scaling. Accurately predicting the time-to-failure of integrated circuits (IC) becomes increasingly important for modern IC design. However, traditional methods are often not sufficiently accurate, leading to undesirable over-design especially in advanced technology nodes. In this paper, we propose an approach using multilayer perceptrons (MLP) to compute stress evolution in the interconnect trees during the void nucleation phase. The availability of a customized trial function for neural network training holds the promise of finding dynamic mesh-free stress evolution on complex interconnect trees under time-varying temperatures. Specifically, we formulate a new objective function considering the EM-induced coupled partial differential equations (PDEs), boundary conditions (BCs), and initial conditions to enforce the physics-based constraints in the spatial-temporal domain. The proposed model avoids meshing and reduces temporal iterations compared with conventional numerical approaches like FEM. Numerical results confirm its advantages on accuracy and computational performance., Comment: The paper will be published in IEEE Transactions on COMPUTER-AIDED DESIGN of Integrated Circuits and Systems