#01Nov 10, 2026
cs.LG
When Does the Real Wiring Win? Testing connectome structure-function claims against unmeasured physiology
Yeyuan Liu
Connectome-constrained models are often used to argue that a measured wiring diagram outperforms shuffled or rewired wiring, and hence that structure shapes function. Such comparisons can confound wiring with how the models are tuned: a connectome fixes who connects to whom, not the excitability, gains or plasticity rates the model also needs, and modellers often tune these until the real-wiring model works. We separate three estimands: physiology tuned on the real wiring and transferred to nulls (P1), each wiring tuned on its own (P2), and P2 restricted to physiology consistent with independent data (P3). The biases involved are known in machine learning (under-tuned baselines, inherited weights, winner's curse); we measure what they do to biological conclusions, using synthetic ground truth, placebo nulls and three Drosophila circuit models. Some claims survive every protocol we test: segregated reward and punishment dopamine improves learning, and head-direction topography is required for a persistent bump. Others do not. In the mushroom body, the real Kenyon-cell output wiring beats a cross-subtype identity shuffle by 0.09 under P1 and P2 but loses to it by 0.09 under P3 (95% CIs exclude zero; held-out runs confirm). The verdict is set by the share of alpha'beta' cells among active Kenyon cells, which P1 selects low; at the share implied by imaging (about 44%) the real-wiring model fails to learn, exposing a model inadequacy rather than a deficit of the fly's wiring. In flyvis, P1 penalises a mirrored connectome, which has a constructed solution within 0.07 (median) of the real error, more than a spatially shuffled one in 50 of 50 members; the ranking survives ten-fold longer retraining but depends on the checkpoint at fifty-fold. A credible structural claim needs matched optimisation, data-constrained physiology and a model that still works there.
#02Nov 10, 2026
cs.LG
Continual-ARC: Measuring Skill Acquisition over a Working Lifetime
Daniel Lenton
Agent harnesses have emerged as a promising mechanism for continual learning, alongside test-time parametric learning. However, the current benchmarks have several limitations: they generally focus on a single applied domain, serve each instance only once, and assume a single family of learner, so memory-based and weight-based systems are rarely compared on the same scale. We propose Continual-ARC, a lifelong stream built from the three ARC-AGI editions, whose tasks need no domain knowledge. The same tasks return after dormant gaps with fresh instances, while new tasks keep arriving. On each instance, the learner may pay for demonstrations, submit answers, or act inside the harness, with retries permitted on incorrect submissions, which are paid for. Each instance is scored based on the share of this feedback budget consumed. Since a learner may keep anything between instances, memory-based and weight-based systems are scored on the same scale. After the stream, the learner is frozen and tested on fresh instances of the tasks it met, which measures memorization, and on unseen tasks, which measures generalization. We run an agent harness with frozen weights, with and without persistence, on Qwen3.5-9B and GLM-5.3 Flash, comparing them with two prompting floors, a program-induction method and Qwen3.5-9B's weights trained to imitate GLM-5.3 Flash. Persistence in the harness generally does not improve memorization unless provided with explicit expert guidance. Most harness-based methods still learn less than a floor that simply caches each task's demonstrations, across all models we tested. No harness-based method gains on unseen tasks, whereas weight-based learning shows substantial gains. This opens the door to future weight-based continual learning that could teach models to drive harnesses in new domains.
#03Nov 10, 2026
cs.CV
Medical Image Segmentation: Foundation Model Adaptation versus Task-Specific Training
Emre Kutlusan, Yongmin Li
Foundation models pretrained on large natural-image collections are increasingly adapted for medical image segmentation, in the expectation that they will replace models trained for each task. Most comparisons, however, use data from the training distribution and a single task-specific baseline whose configuration is rarely justified, and therefore provide limited evidence of performance at new clinical sites. It also remains unclear how much of a foundation model must be adapted, and what determines this. We adapted a foundation model, DINOv2, with strategies ranging from tuning only its bias terms to full fine-tuning, and compared it with U-Nets and ResU-Nets trained from scratch. Experiments covered colonoscopy, breast ultrasound and dermoscopy, with testing on held-out data from the training source and on independent datasets from other institutions. The adapted foundation model generalised better on every external dataset. Within the training distribution, the task-specific models remained competitive when training data were abundant, and delineated boundaries more precisely, while the foundation model more often missed small lesions. Only a small fraction of the foundation model required adaptation, and the capacity needed was determined by the imaging domain rather than by the adaptation method. A widely used polyp test set was also found to duplicate images from another benchmark. Foundation-model adaptation is therefore warranted where models must work across sites, with capacity selected on the target domain.
#04Nov 10, 2026
math.AP
Bayesian inverse problems and epidemic-threshold uncertainty for a heterogeneous SIS reaction-diffusion model
Duc-Lam Duong
We study Bayesian inference of persistence from early observations of a heterogeneous susceptible--infected--susceptible (SIS) reaction--diffusion model with standard incidence. We show that the leading prevalence dynamics depend on the unknown coefficients only through the difference between the transmission and recovery rates and the infected diffusivity. The same pair determines the principal eigenvalue whose sign governs persistence, so early prevalence can inform the threshold even when the individual rates remain uncertain. We prove global weak well-posedness and quantitative parameter stability for the SIS system and use the resulting observation-map estimates to establish Bayesian well-posedness. For an initial infection of size $\varepsilon$, we derive a uniform second-order expansion that describes how the separate rates enter prevalence. Incidence depends explicitly on transmission at leading order. When the noise standard deviation is proportional to $\varepsilon$, we prove $O(\varepsilon)$ convergence in Hellinger distance of the nonlinear posteriors to their low-prevalence limits for both prevalence alone and joint prevalence and incidence data. We bound the principal eigenvalue using the growth rate of the infected $L^2$ norm between two times. This rate gives a lower bound for the full nonlinear system, and the upper bound separates spatial transients from nonlinear saturation. Uniform spectral estimates and bounds on infection size and measurement error give sufficient conditions for persistence and extinction. We also bound the error in posterior persistence probabilities under forward and eigenvalue approximation, accounting for posterior mass near the threshold. Numerical examples illustrate threshold inference and the predicted \(O(\varepsilon)\) convergence of the nonlinear posteriors to their low-prevalence limits in Hellinger distance.
#05Nov 10, 2026
cs.LG
Pyrite: Building and Benchmarking Protein-Ligand Pose Ranking Agents
Megha Srivastava, Michael H. Lim, Allison M. Keys and 2 more
Predicting how a ligand binds to its target is central to small-molecule drug discovery. Modern cofolding models can generate diverse candidate poses, but reliably ranking these candidates remains challenging. We introduce Pyrite, a pairwise pose-ranking benchmark comprising 1,500 pose pairs across diverse protein-ligand complexes. Expert chemists equipped with 3D visualization tools and physics-based scores perform near chance, highlighting the difficulty of interpreting available chemical signals. To investigate automated ranking, we introduce PyriteRep, a structured representation of molecular geometry, protein-ligand interactions, and physicochemical scores, and develop two LLM-based agents: PyriteReasoner, which directly compares poses through text-based reasoning, and PyriteFeaturizer, which generates executable code to construct features for logistic regression, optionally incorporating features derived from LLM subcalls. These agents achieve up to 67% and 74% accuracy, respectively, exceeding observed expert performance. LLM-guided feature discovery generally outperforms direct reasoning, while Group Relative Policy Optimization (GRPO) improves open-weight models, enabling them to match or surpass closed-source frontier models in our evaluations. These results establish Pyrite as a challenging test of pose-ranking ability and highlight LLM-guided feature discovery as a promising approach to interpret and combine the outputs of computational chemistry tools.