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01.
arXiv (CS.CL) 2026-06-15

SuperThoughts: Reasoning Tokens in Superposition

Long Chain-of-Thought (CoT) reasoning improves LLM problem-solving but is computationally expensive due to sequential token generation. While recent works explore reasoning in continuous latent spaces to bypass discrete token generation, they often struggle with training stability and fail to scale to complex, long-horizon tasks due to lack of supervision signal. We propose SuperThoughts, which compresses pairs of consecutive CoT tokens into single latent representations and decodes two tokens per step via a lightweight Multi-Token Prediction (MTP) module. This preserves discrete token supervision at training time while doubling throughput at inference time. We finetune Qwen2.5-Math-1.5B-Instruct, Qwen2.5-Math-7B-Instruct, Qwen2.5-Math-14B-Instruct, and evaluate on MATH500, AMC, OlympiadBench, and GPQA-Diamond. With a confidence-based adaptive mechanism that falls back to standard decoding when uncertain, SuperThoughts achieves $\sim$20–30\% CoT length reduction while maintaining accuracy with minimal degradation (1-2 points accuracy drop on most tasks).

02.
arXiv (quant-ph) 2026-06-24

Perfect State Transfer on Quotient Graphs in Shunt Decomposition-Based Quantum Walks

arXiv:2606.24440v1 Announce Type: cross Abstract: This paper investigates perfect state transfer (PST) in discrete-time quantum walks constructed via the shunt decomposition method. The walks are defined on a graph $G$ and its associated quotient graph $G/\pi$, induced by an equitable partition $\pi$. Through the shunt decomposition of $G$, we derive an explicit relation between the shift operator of the parent graph $G$ and that of its quotient graph $G/\pi$. We construct a reflection operator based on the characteristic matrix, which establishes a connection between the transition operator of the parent graph and that of its lower-dimensional quotient graph. We then prove that PST occurs on $G$ if and only if it occurs on $G/\pi$. Furthermore, we express the unitary evolution operator of the quotient graph in terms of Chebyshev polynomials of the first kind, from which we derive explicit criteria for PST. As an application, we establish PST on the cycle graph $C_{n}$ at time $k = n/2$, and lift the result to the parent graph $C_{2n}$ via the equitable partition $\pi$. We further show that if an equitable partition $\pi$ of $G$ induces a quotient isomorphic to $K_n^{\circlearrowleft}$, the complete digraph on $n$ vertices with a loop at every vertex, then PST occurs at step $k = n$, and the walk is periodic at $k = 2n$. This framework is applied to two families of graphs, which are the complete bipartite digraph $K_{n,n}^{\rightleftharpoons}$ and the circulant graph $\operatorname{Circ}(2n, S)$, where $S$ consists of all odd residues modulo $2n$ and $n = 2^s$ for some $s \geq 1$, establishing PST in their respective line digraphs. Collectively, these results also answer the question posed by Godsil and Zhan concerning which shunt decompositions or embeddings of a graph admit PST.

03.
arXiv (math.PR) 2026-06-24

On the stability of rarefaction for stochastic viscous conservation law

arXiv:2606.24167v1 Announce Type: new Abstract: We study the asymptotic stability of rarefaction waves for one-dimensional stochastic viscous conservation laws driven by nonlinear conservative noise. In a critical scaling where stochastic energy injection and viscous dissipation compete at comparable magnitudes, standard kinetic and viscosity frameworks encounter obstructions due to regularity gaps and non-integrable profiles. To address this, we introduce a stochastic area inequality controlling accumulated energy fluctuations, a local $L^1$ contraction principle via stochastic Kru\v{z}kov doubling-of-variables that yields pathwise uniqueness without global integrability, and a modified Galerkin scheme preserving the $H^2$ energy structure. Assuming local $H^2$ regularity, we prove almost sure algebraic convergence to the rarefaction wave. For sufficiently small initial perturbations, we establish global well-posedness and sharp decay estimates in expectation. The smallness condition identifies a regime where viscous dissipation dominates stochastic injection, reflecting a structural stability threshold rather than a technical artifact. Our approach extends the analytical framework for conservative SPDEs with rough fluxes.

04.
arXiv (CS.LG) 2026-06-24

Precision Physical Activity Prescription via Reinforcement Learning for Functional Actions

arXiv:2605.19208v2 Announce Type: replace-cross Abstract: Physical activity (PA) plays an important role in maintaining and improving health. Daily steps have been a key PA measure that is easily accessible with common wearable devices. However, methods are lacking to recommend a personalized optimal distribution of daily steps over a period of time for the best of certain health biomarkers. In this paper, we fill this void based on the data from the All of Us Research Program which includes months of step counts as well as repeated measurements of key health biomarkers. We develop a new offline reinforcement learning (RL) algorithm to learn personalized and optimal PA distributions associated with cardiometabolic risk, where the action is a function representing the daily step distribution over a period of time. Simulation studies demonstrate the advantage of the proposed approach over existing continuous-action RL methods. The learned optimal policy from the All of Us data generally suggests people take more daily steps and also follow a more consistent pattern of PA over time while offering tailored recommendations for subgroups in blood glucose level, body mass index, blood pressure, age, and sex.

05.
arXiv (CS.CV) 2026-06-17

Rethinking Cross-Layer Information Routing in Diffusion Transformers

Diffusion Transformers (DiTs) have become a de facto backbone of modern visual generation, and nearly every major axis of their design – tokenization, attention, conditioning, objectives, and latent autoencoders – has been extensively revisited. The residual stream that governs how information accumulates across layers, however, has been directly inherited from the original Transformer. In this paper, we present a systematic empirical analysis of cross-layer information flow in DiTs, jointly along depth and denoising timestep, and identify three concrete symptoms of traditional residual addition, namely monotonic forward magnitude inflation, sharp backward gradient decay, and pronounced block-wise redundancy. Motivated by this diagnosis, we propose Diffusion-Adaptive Routing (\textsc{DAR}), a drop-in residual replacement that performs learnable, timestep-adaptive, and non-incremental aggregation over the history of sublayer outputs. Moreover, the proposed \textsc{DAR} is compatible with many modern Transformer enhancement methods, such as REPA. On ImageNet $256\times256$, \textsc{DAR} improves SiT-XL/2 by $2.11$ FID ($7.56$ vs.\ $9.67$) and matches the baseline's converged quality with $8.75\times$ fewer training iterations. Stacked on top of REPA, it yields a $2\times$ training acceleration in the early stage, suggesting cross-layer information routing as an underexplored design axis in diffusion modeling, one that operates orthogonally to existing representation-alignment objectives. Beyond pretraining, \textsc{DAR} can also be applied during the fine-tuning stage of large-scale T2I models and preserves high-frequency details during Distribution Matching Distillation.

06.
arXiv (CS.CL) 2026-06-11

Measuring Semantic Progress in Multi-turn Dialogue via Information Gain

Evaluating multi-turn dialogue is challenging because quality emerges across turns rather than within individual responses. We focus on a key dimension of information-seeking dialogue: semantic progress, defined as the accumulation of new, question-relevant, and non-redundant information over the course of a conversation. We formalize semantic progress as question-conditioned uncertainty reduction and introduce an information-theoretic metric that approximates it in embedding space. Our main estimator uses a tractable Gaussian formulation with closed-form updates, while a complementary maximum-entropy argument shows why log-determinant structure arises more broadly when only second-order embedding information is retained. This formulation yields desirable theoretical properties, including monotonicity, additive decomposition of total information gain across turns, and diminishing returns for redundant evidence. Unlike LLM-as-a-judge approaches, our metric requires no autoregressive inference at evaluation time and is fully reproducible for a fixed embedding model. Experiments on MT-Bench, Chatbot Arena, and UltraFeedback show that the proposed metric achieves competitive agreement with human judgments despite targeting only semantic progress, with improved alignment on MT-Bench and UltraFeedback compared to several LLM-based judges. Notably, the method remains effective with lightweight embedding models under CPU-only execution, indicating that semantic progress can be captured without reliance on large model capacity.

07.
arXiv (CS.CV) 2026-06-16

Selective Synergistic Learning for Video Object-Centric Learning

Typical video object-centric learning (VOCL) approaches employ slot-based frameworks that rely on reconstruction-driven encoder-decoder architectures, where learning is mediated by two spatial maps: attention maps from the encoder and object maps from the decoder. As these two distinct maps exhibit different properties, a recent dense alignment strategy attempted to reconcile this discrepancy by enforcing agreement across all spatio-temporal patches via contrastive learning. However, this indiscriminate alignment inadvertently propagates the inherent weaknesses of each module, such as noisy encoder predictions and blurred decoder boundaries. Moreover, computing dense similarities across all pairs incurs a computational cost quadratic in the total number of spatio-temporal patches, severely limiting scalability. Motivated by this, we propose Selective Synergistic Learning (SSync). Instead of exhaustive patch-to-patch alignment, SSync prevents error propagation by selectively distilling only the most reliable cues: leveraging the encoder strictly for boundary refinement and the decoder for interior denoising. This is realized via a pseudo-labeling with linear complexity, eliminating the need for quadratic spatial comparisons. Also, to prevent the reinforcement of architectural biases like slot redundancy, we introduce a transitive pseudo-label merging that consolidates overlapping slots based on spatio-temporal activation consistency. Extensive studies demonstrate that SSync improves decomposition quality and serves as a versatile, plug-and-play module while also exhibiting exceptional robustness to slot configurations. Code is available at github.com/wjun0830/SSync.

08.
arXiv (CS.CL) 2026-06-16

Retrievable Gradients: Continual Post-Training Without Cumulative Weight Drift

Continual post-training enables models to absorb emerging knowledge after deployment, but repeatedly updating shared parameters can accumulate weight drift, potentially causing catastrophic forgetting and degrading general capabilities. Retrieval-augmented generation avoids such parameter drift, yet often lacks the depth of parametric knowledge integration. In this paper, we propose ReGrad (Retrievable Gradients), a new paradigm that treats gradients as retrievable units of knowledge. ReGrad pre-computes document-specific gradients offline, stores them in an indexed Gradient Bank, and retrieves only query-relevant gradients at inference time for temporary weight adaptation. However, raw language-modeling gradients are optimized for token-level document reconstruction rather than for query-driven knowledge use. We therefore introduce a bi-level meta-learning objective that reshapes document-derived gradients into generalizable adaptation signals for downstream tasks. Experiments across general and domain-specific settings show that \textsc{ReGrad} outperforms CPT and RAG baselines, enabling scalable and reversible parametric knowledge injection without accumulating weight drift.

09.
arXiv (CS.CL) 2026-06-24

The African Language Tax: Quantifying the Cost, Latency, and Context Penalty of Tokenizing African Languages in Frontier LLMs

Commercial large language models bill, scale latency, and budget context per token. Yet tokenizers assign more subword tokens to the same meaning in some languages than in others, so speakers of languages with high token-fertility pay a structural penalty before a model is ever invoked. This penalty is documented for multilingual settings in general, but it has not been measured systematically for African languages at the level of enterprise deployment economics and cognitive context capacity. We measure it across 20 African languages spanning five language families and three scripts (Latin, Ge'ez/Ethiopic, N'Ko; 19 appear in the primary FLORES-200+ corpus, with Nigerian Pidgin measured via MAFAND-MT only), using parallel corpora so that the language effect is isolated from content. Across 11 frontier and open tokenizers on FLORES-200+, every African language carries a tokenization premium above English (median 1.88x on GPT-5 / o200k_base, up to 8.92x for N'Ko); the penalty is largest for Ethiopic and N'Ko scripts (reaching 7-9x) and is near-invariant across corpora (FLORES vs SIB-200 Pearson r = 0.9998). Translated into deployment terms, this results in up to 8.9x inference cost and an equivalent generation-latency multiplier (N'Ko vs English on GPT-5; 7.4x for Amharic), and as little as 11% of English's effective context window. The best currently available tokenizer for African languages, Gemma 4, reduces the mean premium from 3.31x (cl100k_base) to 2.38x, but no tokenizer eliminates the penalty. We release an open measurement tool (afri-fertility), a public leaderboard, a results dataset, and mitigation guidance for African builders. The penalty falls hardest on the languages whose speakers can least afford it, a digital divide encoded directly into the subword vocabulary.

10.
arXiv (CS.LG) 2026-06-24

HyMaTE: A Hybrid Mamba and Transformer Model for EHR Representation Learning

arXiv:2509.24118v2 Announce Type: replace Abstract: Electronic health Records (EHRs) have become a cornerstone in modern-day healthcare. They are a crucial part for analyzing the progression of patient health; however, their complexity, characterized by long, multivariate sequences, sparsity, and missing values poses significant challenges in traditional deep learning modeling. While Transformer-based models have demonstrated success in modeling EHR data and predicting clinical outcomes, their quadratic computational complexity and limited context length hinder their efficiency and practical applications. On the other hand, State Space Models (SSMs) like Mamba present a promising alternative offering linear-time sequence modeling and improved efficiency for handling long sequences, but focus mostly on mixing sequence-level information rather than channel-level data. To overcome these challenges, we propose HyMaTE (A Hybrid Mamba and Transformer Model for EHR Representation Learning), a novel hybrid model tailored for representing longitudinal data, combining the strengths of SSMs with advanced attention mechanisms. By testing the model on predictive tasks on multiple clinical datasets, we demonstrate HyMaTE's ability to capture an effective, richer, and more nuanced unified representation of EHR data. Additionally, the interpretability of the outcomes achieved by self-attention illustrates the effectiveness of our model as a scalable and generalizable solution for real-world healthcare applications. Codes are available at: https://github.com/healthylaife/HyMaTE.

11.
arXiv (CS.AI) 2026-06-11

Compiler-First State Space Duality and Portable $O(1)$ Autoregressive Caching for Inference

arXiv:2603.09555v2 Announce Type: replace-cross Abstract: High-throughput Mamba-2 inference is usually tied to fused CUDA and Triton kernels, limiting portability across accelerator backends. We show that the state space duality (SSD) recurrence has a compiler-friendly structure: diagonal per-head dynamics, fixed-size chunking, einsum-dominated compute, and static control flow. Expressing this structure in standard JAX primitives gives a single-source inference path with no custom kernels, a registered JAX PyTree cache, and a compiled on-device autoregressive loop. On a single Google Cloud TPU v6e, batch-1 prefill reaches approximately 140 TFLOPS, or 15% model FLOP utilisation (MFU), the roofline ceiling for this regime, and cached decode reaches up to 64% hardware bandwidth utilisation (HBU). At a 4096-token context, cached decode is 27x–36x faster than full-prefix recomputation across five Mamba-2 checkpoints from 130M to 2.7B parameters. The same source runs unmodified on NVIDIA L40S, where cached decode remains sequence-length independent across all model scales. WikiText-103 validation perplexity matches the Triton reference mamba_ssm v2.2.2 within +/-0.0005 points, and hidden states agree to float32 rounding tolerance. Code is available at https://github.com/CosmoNaught/mamba2-jax.

12.
arXiv (CS.CV) 2026-06-15

Improving Lunar Topography with Deep Learning Schrödinger Bridges

Increasing the resolution of planetary topography models can enable a better understanding of surface processes and geomorphology; however, existing analytical super-resolution methods are expensive and difficult to apply at large scales. Generative models provide the tools to learn complex relationships within data and can be applied at scale due to hardware accelerators and parallelization. We present a diffusion-based Schrödinger Bridge (SB) generative modeling approach for lunar topography super-resolution, connecting the distribution of low-resolution topography to that of high-resolution topography, incorporating physically-constraining optical imagery. Our approach is inspired by existing Shape-from-Shading methods, which improve a priori low-resolution topography by using optical images at the target resolution. We train SBs on a novel dataset of rendered lunar topography, emulating optical imagery from the Lunar Reconnaissance Orbiter Narrow Angle Camera. The result is a flexible approach for topography super-resolution which can provide pixel-level uncertainties in the reconstruction.

13.
arXiv (CS.AI) 2026-06-11

MoCA-Agent: A Market-of-Claims Code Agent for Financial and Numerical Reasoning

arXiv:2606.11537v1 Announce Type: new Abstract: Financial and tabular question answering requires more than fluent reasoning: answers must be grounded in the exact facts, formulas, units, signs, and scales that support them. A single misread cell or incorrect operation can silently produce a plausible but wrong result. We introduce \textsc{MOCA-Agent}, a market-of-claims code agent that replaces free-form multi-agent debate with claim-level verification. The system decomposes each question into typed atomic claims, asks specialist trader agents to buy or sell those claims, clears their orders into confidence-weighted accept/reject decisions, and synthesizes an executable Python program from market-supported evidence. A code-aware verifier then checks the program for execution, structural consistency, and common financial reasoning errors, with at most one market-aware repair round. Across ten public benchmarks spanning financial numerical reasoning, general tabular reasoning, ESG question answering, and multimodal chart reasoning, \textsc{MOCA-Agent} achieves strong performance using a fixed Qwen3.6-27B backbone, including $78.3\%$ on FinQA, $76.0\%$ on FinanceMath, $71.2\%$ on MultiHiertt, $86.9\%$ on ESGenius, and $85.6\%$ average on FinChart-Bench. These results show that aggregating evidence at the level of atomic claims, rather than whole answers, improves robustness in high-stakes numerical reasoning.\footnote{The code and data are available: https://github.com/UBC-NLP/MoCA-Agent.

14.
arXiv (CS.CV) 2026-06-11

EvoLMM: Self-Evolving Large Multimodal Models with Continuous Rewards

Recent advances in large multimodal models (LMMs) have enabled impressive reasoning and perception abilities, yet most existing training pipelines still depend on human-curated data or externally verified reward models, limiting their autonomy and scalability. In this work, we strive to improve LMM reasoning capabilities in a purely unsupervised fashion (without any annotated data or reward distillation). To this end, we propose a self-evolving framework, named EvoLMM, that instantiates two cooperative agents from a single backbone model: a Proposer, which generates diverse, image-grounded questions, and a Solver, which solves them through internal consistency, where learning proceeds through a continuous self-rewarding process. This dynamic feedback encourages both the generation of informative queries and the refinement of structured reasoning without relying on ground-truth or human judgments. When using the popular Qwen2.5-VL as the base model, our EvoLMM yields consistent gains upto $\sim$3\% on multimodal math-reasoning benchmarks, including ChartQA, MathVista, and MathVision, using only raw training images. We hope our simple yet effective approach will serve as a solid baseline easing future research in self-improving LMMs in a fully-unsupervised fashion. Our code and models are available at https://github.com/mbzuai-oryx/EvoLMM.

15.
arXiv (CS.LG) 2026-06-15

DTVEM-RE: A Hierarchical Random-Effects Extension of the Differential Time-Varying Effect Model for Person-Specific Multi-Lag Estimation in Intensive Longitudinal Data

arXiv:2606.14116v1 Announce Type: new Abstract: The Differential Time-Varying Effect Model (DTVEM) of Jacobson et al. (2019) is a popular tool for finding the best time lag in intensive longitudinal data, but it assumes everyone shares the same lag structure. The original authors named fixing this as future work, and it clashes with the premise of modern clinical research, which is that people differ. We present DTVEM-RE, an extension that lets each person have their own lag coefficients, with two versions of the confirmatory step: a discrete-time hierarchical Bayesian VAR in Stan, which pools across people and gives calibrated uncertainty, and a continuous-time per-person Ornstein-Uhlenbeck model in ctsem, which handles unevenly spaced beeps directly. We report four results. A simulation shows the Bayesian version recovers the between-person spread tau_a with bias below 0.01 and coverage of 90 to 93 percent. On the Fisher et al. (2017) EMA dataset (N=40), person-specific lag-1 effects vary by an order of magnitude across three mood items, the Bayesian and GAMM estimates agree closely (r=0.87 to 0.92), and DTVEM-RE gives the best one-step-ahead prediction among four discrete-time methods. A multi-lag version shows all nine tau_k values have credible intervals excluding zero, and the lag where people differ most changes across items, something lag-1-only methods like mlVAR cannot detect. Finally, the two versions agree almost exactly on person-specific lag-1 estimates (r >= 0.995), differing only as shrinkage predicts. DTVEM-RE is, to our knowledge, the first person-specific implementation of DTVEM-style lag detection, and it contains standard DTVEM as a special case.

16.
arXiv (CS.LG) 2026-06-16

If These Walls Could Talk: Critical Play with Large Language Models in Museums

arXiv:2606.15565v1 Announce Type: cross Abstract: Large Language Models (LLMs) are increasingly being used in museums to as role playing chatbots which let visitors talk to simulated versions of people and artefacts from the past. While such installations can be playful and engaging, they are also problematic because LLMs cannot be trusted to speak truthfully. I identify a fundamental dilemma for the use of LLMs in museum chatbots: LLMs cannot be trusted to tell the truth, and efforts to make them more reliable may ruin that which is attractive about the bots in the first place - their ability to engage in life-like conversation. In response, I propose designing for critical play with LLM-based bots: Designing for playful interactions with bots that are unreliable but still able to represent the past in an adequate and engaging manner - as fictional characters representing historical narratives, styles of discourse, diverse perspectives, humor and satire.

17.
bioRxiv (Bioinfo) 2026-06-11

An AI-Powered Trisomy 21 Research Assistant

Down syndrome, caused by trisomy 21, increases the risk of diverse co-occurring conditions. With more than 34,000 related publications indexed in PubMed as of early 2026, keeping pace with this expanding literature is challenging. While general-purpose large language models are widely used for information retrieval, they often rely on broad training data rather than specific evidence. Retrieval-augmented generation (RAG) improves rigor and reliability of responses by linking model outputs to source texts. In research, source texts are peer-reviewed articles. Standard implementations treat all manuscript sections equally, allowing background text to rank as highly as experimental results. To focus model outputs on experimentally supported responses, we developed the T21 Research Assistant, a section-aware RAG system that prioritizes Results sections to ground responses in primary experimental evidence. The system draws exclusively from 1,789 open-access Down syndrome publications from PubMed Central, including 327 NIH INCLUDE-funded studies, and uses a multistage pipeline for query validation, retrieval, reranking, synthesis, and citation verification. Built on NVIDIA Nemotron models, it generates structured, cited responses. Evaluation using expert-curated questions demonstrated strong performance, achieving a BERTScore F1 of 0.712 and recall of 0.758, comparable to or exceeding leading proprietary and open-source models. T21 Research Assistant is available at: https://bioinformatics.cuanschutz.edu/t21-res-assi/

18.
arXiv (CS.AI) 2026-06-15

Minim: Privacy-Aware Minimal View for Agents via Trusted Local Sanitization

arXiv:2606.13949v1 Announce Type: new Abstract: Modern LLM-powered autonomous agents increasingly rely on rich user interface (UI) state observations to achieve reliable action grounding in complex digital environments. However, many deployments transmit the full UI state to remote inference servers even when most elements are irrelevant to the current task, which can leak sensitive but unnecessary context such as authentication codes, private notifications, and background application states. We propose MINIM, a trusted local broker that performs privacy-aware minimization on the client side before any observation leaves the device. Grounded in Contextual Integrity (CI), MINIM learns a dual-score representation for each UI element by predicting an inherent sensitivity score (s) and a task-conditioned necessity score (n). These scores drive a ternary disclosure policy that keeps essential elements, abstracts sensitive attributes when needed, and removes task-irrelevant content. We optimize a CI-aware objective that penalizes necessity errors more strongly on high-risk content, enabling aggressive pruning while preserving task-critical information. Experiments on real-world UI observations derived from WebArena show that MINIM substantially reduces task-irrelevant sensitive leakage while preserving task-critical semantic context and the interactive affordances required for reliable agent actions.

19.
arXiv (CS.CL) 2026-06-18

Depth-Width tradeoffs in Algorithmic Reasoning of Graph Tasks with Transformers

Transformers have revolutionized the field of machine learning. In particular, they can be used to solve complex algorithmic problems, including graph-based tasks. In such algorithmic tasks a key question is what is the minimal size of a transformer that can implement the task. Recent work has begun to explore this problem for graph-based tasks, showing that for sub-linear embedding dimension (i.e., model width) logarithmic depth suffices. However, an open question, which we address here, is what happens if width is allowed to grow linearly, while depth is kept fixed. Here we analyze this setting, and provide the surprising result that with linear width, constant depth suffices for solving a host of graph-based problems. This suggests that a moderate increase in width can allow much shallower models, which are advantageous in terms of inference and train time. For other problems, we show that quadratic width is required. Our results demonstrate the complex and intriguing landscape of transformer implementations of graph-based algorithms. We empirically investigate these trade-offs between the relative powers of depth and width and find tasks where wider models have the same accuracy as deep models, while having much faster train and inference time due to parallelizable hardware.

20.
medRxiv (Medicine) 2026-06-22

Midlife Measures of General Cognitive Performance in the National Longitudinal Study of Adolescent to Adult Health (Add Health)

Objective: The Add Health Cognitive Assessment, Physical, and Sensory Function Protocol (Add CAPS) was developed to assess cognitive, physical, and sensory function in early midlife in a nationally representative sample in the United States. Using Add CAPS, we developed two general cognitive performance measures. Methods: The sample included 2,525 participants from Add Health Wave VI who completed an in- home assessment of cognitive performance. Confirmatory factor analysis (CFA) was used to derive two general cognitive performance (GCP) scores: (1) a five-domain score based on originally designed cognitive domains (Add CAPS GCP), and (2) a modified score aligned with the Harmonized Cognitive Assessment Protocol (HCAP) framework (Add CAPS GCP-H). We evaluated model fit using Root Mean Square Error of Approximation (RMSEA), Standardized Root Mean Square Residual (SRMR), and Comparative Fit Index (CFI) and tested factor scores for criterion validity. Results: Both models showed good fit (Add CAPS GCP: RMSEA = 0.025, SRMR = 0.031, CFI = 0.968; Add CAPS GCP-H: RMSEA = 0.027, SRMR = 0.033, CFI = 0.962), indicating that they adequately represent the underlying GCP construct. Discussion: The Add CAPS cognitive battery captures a robust, hierarchical structure of GCP across alternative domain specifications. The derived factor scores provide a valuable method for characterizing a person's cognitive baseline during midlife. Importantly, the Add CAPS GCP-H enhances comparability with the HCAP network, supporting cross-cohort analyses of cognitive aging.

21.
Nature (Science) 2026-06-24

Zero-shot design of drug-binding proteins via neural iterative selection−expansion

Authors:

The design of proteins that bind to small molecules has been challenging because it requires simultaneous optimization of the protein sequence, protein structure and ligand conformation1–7. Current deep-learning algorithms have struggled to navigate this landscape, precluding the zero-shot design of binders. Here we show that by combining two neural networks in an iterative design algorithm, small-molecule binding proteins can be created from scratch with high accuracy. We trained a graph neural network—ligand-aware sequence engineering message-passing neural network (LASErMPNN)—to design compatible protein sequences for an input protein backbone and docked ligand. We paired  LASErMPNN with a structure predictor that models a three-dimensional protein–ligand complex for an input protein sequence and ligand identity. The closed-loop iteration of these reciprocal networks optimized sequence–structure–ligand compatibility, and outperformed a comparable design loop using a physics-based energy function. We used our strategy, termed neural iterative selection–expansion (NISE), to design proteins that, using different folds, specifically bind to two chemically distinct small-molecule drugs, exatecan and apixaban, with success rates of 100% and 83%, respectively. The tightest NISE binders had nanomolar-to-picomolar affinities, surpassing those of the next-leading method by 70-fold for exatecan and nearly 10,000-fold for apixaban. LASErMPNN then suggested two amino-acid substitutions that improved the affinity of the tightest exatecan binder by 100-fold without any experimental input. The optimized binder protected the labile lactone ring of exatecan from hydrolysis for days. Our work describes a general recipe for using neural networks to automate the design of small-molecule binding proteins for applications in drug delivery, sensing and catalysis.  By pairing two neural networks in an iterative optimization algorithm, small-molecule binding proteins can be designed from scratch with high accuracy, affinity and success rates, showing promise for applications in drug delivery and sequestration.

22.
bioRxiv (Bioinfo) 2026-06-16

Programmatic access to ICTV virus taxonomy through a public ontology API

The International Committee on Taxonomy of Viruses (ICTV) is responsible for developing and maintaining a universal virus taxonomy. As the reference framework for organising the viral world, it is essential for virology and related fields. Despite its widespread use in research and public health, programmatic access to ICTV taxonomy has remained limited, posing challenges for integration, versioning, and interoperability across databases and bioinformatics resources requiring up-to-date virus taxonomy. To address this, we developed a public and sustainable solution leveraging ontology-based APIs. Successive ICTV Master Species List (MSL) releases were transformed into a structured ontology and deployed as a unified representation through the Ontology Lookup Service (OLS). The framework also provides ICTV-NCBI mappings and helper libraries for integration into downstream systems. This enables, for the first time, public programmatic retrieval of current and historical virological taxon names, taxonomic relationships, metadata, and persistent identifiers through stable endpoints. More broadly, this work illustrates a general strategy for transforming structured biological datasets into semantically enriched graph resources exposed through scalable public APIs. These developments enhance interoperability, reduce manual curation, and support FAIR-aligned taxonomic data management in virology and pandemic preparedness.

23.
arXiv (CS.LG) 2026-06-12

Loss-Shift Transfer via Bayes Quotients

arXiv:2606.13178v1 Announce Type: new Abstract: Transfer learning is usually studied as a consequence of distribution shift. This paper identifies an orthogonal failure mode in which the data distribution is fixed and the loss changes. This setting is called loss shift. A loss determines which information in \(X\) is Bayes-relevant, and two losses may therefore require different representations even under the same joint law \(P(X,Y)\). The idea is formalized using Bayes quotients, which allow losses to be ordered by refinement. In the Bayes-quotient formulation, strict refinement gives an immediate qualitative obstruction. A source-minimal representation for a coarser loss is insufficient for a strictly finer target loss. For finite-output log loss, this obstruction becomes an exact quantitative identity. The excess risk is the conditional information about \(Y\) discarded by the representation. Experiments in controlled, learned, synthetic-image, and real-image settings show the predicted effect, i.e., classification-equivalent representations can have different optimal log-loss performance under a fixed data distribution.

24.
arXiv (CS.CL) 2026-06-15

CoRe: A Continuously Reward-Finetuned LLM Query Rewriter for Multi-Stage Context-Aware Relevance in Web-Scale Video Search

LLM-based query rewriters in production face a tension: the training reward must reflect how the rewrite is consumed by the production ranker, yet the training procedure must be cheap enough to support continuous redeployment as data drifts. We present CoRe (Context Relevance), such a system, redeployed weekly for over five months in a major short-video search engine. Our reward uses the deployed multimodal relevance model as its source and a multiplicative ratio form mirroring the production fusion algebra, closing the simulation-production gap that offline reward proxies leave open. A semi-online Mixed Preference Optimization loop makes this reward affordable at multi-million-instance weekly scale: a DPO-style pairwise objective restricts the gradient pass to a small top-k/bottom-k subset of sampled trajectories, and a phase structure reduces trainer/inference-server parameter syncs from per-step to per-phase. An automated promotion gate over reward-like and stability metrics detected and recovered from a real reward-hacking incident in production. Rewriter output is consumed as parallel relevance signals at recall, rawrank, and finerank without displacing the original signals, bounding rewriter-failure blast radius. Online A/B from two sequential production launches, first deploying the rewriter at finerank, then extending consumption to recall and rawrank, delivers statistically significant reductions in change-query rate on rewrite-impacted queries, with all headline relevance and engagement metrics moving in the expected direction.

25.
arXiv (quant-ph) 2026-06-12

Entanglement Detection by Approximate Entanglement Witnesses

arXiv:2402.14755v2 Announce Type: replace Abstract: The problem of determining whether a given quantum state is separable is known to be computationally difficult. We develop an approach to this problem based on approximations of convex polytopes in high dimensions. By showing that a convex polytope constructed from a finite number of hyperplanes approximates the Euclidean ball arbitrarily well in high dimensions, we find evidence that a finite set of approximate entanglement witnesses is potentially sufficient to determine the entanglement of a state with high probability.