Abstract--T cell receptor (TCR) repertoires encode critical immunological signatures for autoimmune diseases, yet their clinical application remains limited by sequence sparsity and low witness rates. We developed EAMil, a multi-instance deep learning framework that leverages TCR sequencing data to diagnose systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) with exceptional accuracy. By integrating Prime-Seq feature extraction with ESMonehot encoding and enhanced gate attention mechanisms, our model achieved state-of-the-art performance with AUCs of 98.95% for SLE and 97.76% for RA. EAMIL successfully identified disease-associated genes with over 90% concordance with established differential analyses and effectively distinguished disease-specific TCR genes. The model demonstrated robustness in classifying multiple disease categories, utilizing the SLEDAI score to stratify SLE patients by disease severity as well as to diagnose the site of damage in SLE patients, and effectively controlling for confounding factors such as age and gender . This interpretable framework for immune receptor analysis provides new insights for autoimmune disease detection and classification with broad potential clinical applications across immune-mediated conditions.

A central mechanism in machine learning is to identify, store, and recognize patterns. How to learn, access, and retrieve such patterns is crucial in Hopfield networks and the more recent transformer architectures.

Autonomous skill discovery aims to enable robots to acquire diverse behaviors without explicit supervision. Learning such behaviors directly on physical hardware remains challenging due to safety and data efficiency constraints. Existing methods, including Quality-Diversity Actor-Critic (QDAC), require manually defined skill spaces and carefully tuned heuristics, limiting real-world applicability. We propose Unsupervised Real-world Skill Acquisition (URSA), an extension of QDAC that enables robots to autonomously discover and master diverse, high-performing skills directly in the real world. We demonstrate that URSA successfully discovers diverse locomotion skills on a Unitree A1 quadruped in both simulation and the real world. Our approach supports both heuristic-driven skill discovery and fully unsupervised settings. We also show that the learned skill repertoire can be reused for downstream tasks such as real-world damage adaptation, where URSA outperforms all baselines in 5 out of 9 simulated and 3 out of 5 real-world damage scenarios. Our results establish a new framework for real-world robot learning that enables continuous skill discovery with limited human intervention, representing a significant step toward more autonomous and adaptable robotic systems. Demonstration videos are available at https://adaptive-intelligent-robotics.github.io/URSA.

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A central mechanism in machine learning is to identify, store, and recognize patterns. How to learn, access, and retrieve such patterns is crucial in Hopfield networks and the more recent transformer architectures.

An active approach to fault tolerance is essential for long term autonomy in robots -- particularly multi-robot systems and swarms. Previous efforts have primarily focussed on spontaneously occurring electro-mechanical failures in the sensors and actuators of a minority sub-population of robots. While the systems that enable this function are valuable, they have not yet considered that many failures arise from gradual wear and tear with continued operation, and that this may be more challenging to detect than sudden step changes in performance. This paper presents the Artificial Antibody Population Dynamics (AAPD) model -- an immune-inspired model for the detection and diagnosis of gradual degradation in robot swarms. The AAPD model is demonstrated to reliably detect and diagnose gradual degradation, as well as spontaneous changes in performance, among swarms of robots of as few as 5 robots while remaining tolerant of normally behaving robots. The AAPD model is distributed, offers supervised and unsupervised configurations, and demonstrates promising scalable properties. Deploying the AAPD model on a swarm of foraging robots undergoing slow degradation enables the swarm to operate at an average of ~79\% of its performance in perfect conditions.

Model checking of strategic abilities for agents with memory is a notoriously hard problem, and very few attempts have been made to tackle it. In this paper, we present two important steps towards this goal. First, we take the partial-order reduction scheme that was recently proved to preserve individual and coalitional abilities of memoryless agents, and show that it also works for agents with memory. Secondly, we take the Knowledge-Based Subset Construction, that was recently studied for synchronous concurrent games, and adapt it to preserve abilities of memoryful agents in asynchronous MAS. On the way, we also propose a new execution semantics for strategies in asynchronous MAS, that combines elements of Concurrent Game Structures and Interleaved Interpreted Systems in a natural and intuitive way.

A central question in human immunology is how a patient's repertoire of T cells impacts disease. Here, we introduce a method to infer the causal effects of T cell receptor (TCR) sequences on patient outcomes using observational TCR repertoire sequencing data and clinical outcomes data. Our approach corrects for unobserved confounders, such as a patient's environment and life history, by using the patient's immature, pre-selection TCR repertoire. The pre-selection repertoire can be estimated from nonproductive TCR data, which is widely available. It is generated by a randomized mutational process, V(D)J recombination, which provides a natural experiment. We show formally how to use the pre-selection repertoire to draw causal inferences, and develop a scalable neural-network estimator for our identification formula. Our method produces an estimate of the effect of interventions that add a specific TCR sequence to patient repertoires. As a demonstration, we use it to analyze the effects of TCRs on COVID-19 severity, uncovering potentially therapeutic TCRs that are (1) observed in patients, (2) bind SARS-CoV-2 antigens in vitro and (3) have strong positive effects on clinical outcomes.

The arrival of Large Language Models (LLMs) has stirred up philosophical debates about the possibility of realizing agency in an artificial manner. In this work we contribute to the debate by presenting a theoretical model that can be used as a threshold conception for artificial agents. The model defines agents as systems whose actions and goals are always influenced by a dynamic framework of factors that consists of the agent's accessible history, its adaptive repertoire and its external environment. This framework, in turn, is influenced by the actions that the agent takes and the goals that it forms. We show with the help of the model that state-of-the-art LLMs are not agents yet, but that there are elements to them that suggest a way forward. The paper argues that a combination of the agent architecture presented in Park et al. (2023) together with the use of modules like the Coscientist in Boiko et al. (2023) could potentially be a way to realize agency in an artificial manner. We end the paper by reflecting on the obstacles one might face in building such an artificial agent and by presenting possible directions for future research.

The human immune response depends on the binding of T-cell receptors (TCRs) to antigens (pTCR), which elicits the T cells to eliminate viruses, tumor cells, and other pathogens. The ability of human immunity system responding to unknown viruses and bacteria stems from the TCR diversity. However, this vast diversity poses challenges on the TCR-antigen binding prediction methods. In this study, we propose a Masked Language Model (MLM), referred to as tcrLM, to overcome limitations in model generalization. Specifically, we randomly masked sequence segments and train tcrLM to infer the masked segment, thereby extract expressive feature from TCR sequences. Meanwhile, we introduced virtual adversarial training techniques to enhance the model's robustness. We built the largest TCR CDR3 sequence dataset to date (comprising 2,277,773,840 residuals), and pre-trained tcrLM on this dataset. Our extensive experimental results demonstrate that tcrLM achieved AUC values of 0.937 and 0.933 on independent test sets and external validation sets, respectively, which remarkably outperformed four previously published prediction methods. On a large-scale COVID-19 pTCR binding test set, our method outperforms the current state-of-the-art method by at least 8%, highlighting the generalizability of our method. Furthermore, we validated that our approach effectively predicts immunotherapy response and clinical outcomes on a clinical cohorts. These findings clearly indicate that tcrLM exhibits significant potential in predicting antigenic immunogenicity.