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01.
medRxiv (Medicine) 2026-06-22

Nutrient Composition of Foods Represented in the U.S. Food and Nutrient Database for Dietary Studies, 2013-2023

Background: The U.S. Food and Nutrient Database for Dietary Studies (FNDDS) is updated across NHANES dietary cycles and is central to U.S. nutrition surveillance. However, multi-cycle food-code-level changes in nutrient composition have not been comprehensively characterized across the full WWEIA nutrient panel. Objective: To characterize ten-year temporal patterns in nutrient composition across five FNDDS cycles, evaluate pandemic-period food-code compositional stability, and distinguish exploratory mean-level signals from distributional heterogeneity that may reflect reformulation, database coverage, or food-code definition changes. Methods: We analyzed five consecutive FNDDS biennial releases: 2013-14, 2015-16, 2017-18, 2019-20, and 2021-23. Nutrient values were extracted from the public FNDDS/FoodData Central release files and standardized to per-100-g food-code-level records. Cycle midpoints, 2013.5, 2015.5, 2017.5, 2019.5, and 2022.0, served as the independent variable in an exploratory ordinary least squares (OLS) regression. Mann-Kendall testing assessed monotonic rank trends, Welch's ANOVA assessed food-code-level distributional heterogeneity, and pairwise Welch comparisons with Cohen's d summarized pre-pandemic, pandemic-period, and post-pandemic differences. Equivalence testing using TOST with +/-10% bounds was restricted to the 2019-20 versus 2021-23 stability comparison. OLS sensitivity analyses were repeated after excluding the structurally atypical 2017-18 cycle. Results: Sixty-three nutrients were analyzed. Eight nutrients showed nominal OLS trends, p < 0.05, but none remained significant after Bonferroni correction. Mann-Kendall testing identified two nominal monotonic signals, and none after adjustment. Welch's ANOVA detected cycle-level distributional differences for 61 of 63 nutrients at nominal p < 0.05 and 57 of 63 after adjustment. Pairwise pandemic-period analyses showed many adjusted differences when the pre-pandemic baseline was compared with 2019-20 or 2021-23, but standardized effects were small, with all absolute Cohen's d values < 0.20. No nutrient differed after adjustment between 2019-20 and 2021-23, and 39 of 48 primary analytes met +/-10% TOST equivalence criteria for that comparison. Slope estimates were directionally stable after excluding 2017-18, but nominal significance status remained sensitive to the short time series. Conclusions: FNDDS food composition varied across cycles, but there was no clear decade-long linear trend for most nutrients. The main signal was a possible increase in total PUFA and linoleic acid, which may reflect changes in fat quality. The 2021-23 cycle was very similar to 2019-20, suggesting no major post-pandemic shift in the foods represented. These findings should be interpreted as food-database signals, not as direct estimates of what people consumed.

02.
arXiv (CS.LG) 2026-06-17

Damage Adaptation in Seconds for Architected Materials

arXiv:2606.17394v1 Announce Type: cross Abstract: Adaptation to damages and in-situ physical repairs is essential for long-term robot autonomy, yet challenging outside of narrowly defined and well-anticipated bounds. In this work we proprioceptively adapt to catastrophic damage in soft-actuated systems in under one minute. Architected materials are well equipped for adaptation: actuator failure occurs gradually rather than acutely, and damage can be described in a low-dimensional, discrete coordinate space. Surprisingly, latent damage representations plus a simple yet robust ensemble method is sufficient for adapting to unseen damage in real-time. Moreover, we identify conditions under which exponential sample complexity collapses to linear sample complexity for learned representations of architected materials, a concrete advantage over rigid components or continuum soft mechanisms. We demonstrate LEAP, our method for adaptive proprioception, via a tracing task for a 6DoF soft wrist based on Handed Shearing Auxetic (HSA) actuators. Our algorithm is able to adapt to cuts, burns, and actuator repairs, enabling simulation-free real-time adaptation that is critical for realizing the promise of soft robots outside the lab. Videos and more information are available at https://murpheylab.github.io/leap.

03.
arXiv (CS.AI) 2026-06-16

NVMOS: Non-Verbal Vocalization Quality Assessment in Speech

arXiv:2606.15888v1 Announce Type: cross Abstract: Non-verbal vocalizations (NVs), such as laughter, sighs, and coughs, are important acoustic cues for emotion and intent. Existing speech quality assessment methods typically focus on overall naturalness, while non-verbal TTS evaluations mainly examine whether a target NV appears with the correct type and position. However, the perceptual quality of NV events themselves remains underexplored. To address this gap, we construct an NV-MOS dataset containing outputs from multiple NV-TTS systems and naturally occurring NV samples, with ratings collected from three acoustic experts on a perceptual quality scale. We further analyze audio-capable multimodal large language models such as Gemini and find clear inconsistencies between their scores and expert ratings. These results suggest that general-purpose multimodal models cannot reliably replace human judgments for NV quality assessment. We then propose NVMOS, to our knowledge the first model that can reliably predict the perceptual quality of NV events in speech. Experimental results show that, with a local NV-event focusing module, NVMOS reaches expert-level or stronger agreement with human MOS.

04.
arXiv (CS.CL) 2026-06-15

Automatic identification of diagnosis from hospital discharge letters via weakly supervised Natural Language Processing

Identifying patient diagnoses from hospital discharge letters is essential for large-scale cohort selection and epidemiological research, but traditional supervised approaches require extensive manual annotation, which is often impractical for large textual datasets. We present a weakly supervised Natural Language Processing (NLP) pipeline for classifying Italian discharge letters without document-level manual annotation. The method extracts diagnosis-related sentences, generates semantic embeddings using a transformer model further pre-trained on Italian medical documents, and applies a two-level clustering procedure to derive weak labels that are then used to train a document-level classifier. The approach was evaluated in a case study on bronchiolitis using 33,176 discharge letters of children admitted to 44 emergency rooms or hospitals in the Veneto Region, Italy, between 2017 and 2020. The best weakly supervised model achieved an AUROC of 77.68% ($\pm4.30\%$), an AUPRC of 73.13% ($\pm4.93\%$), and an F1-score of 78.14% ($\pm4.89\%$) against manually annotated data. Performance surpassed unsupervised baselines and approached fully supervised models, while reducing the need for manual annotation by more than 1,500 hours for a dataset of this size. Similar model rankings were observed in a secondary validation on a smaller bronchitis dataset (3,188 discharge letters, 2020-2025), where the best weakly supervised model achieved an AUPRC of 76.72% ($\pm 5.02\%$). These results suggest the potential of weakly supervised NLP methods for scalable disease identification from clinical discharge letters.

05.
arXiv (CS.LG) 2026-06-18

Shrinkage priors for Bayesian Substitute Confounders

arXiv:2606.18535v1 Announce Type: cross Abstract: Multi-cause observational studies contain information about unmeasured confounding through the dependence structure among causes. However, literal imputation of the unobserved confounder is often more complex than learning a lower-dimensional substitute score that preserves the shared assignment variation needed for stable causal adjustment. The deconfounder (Wang and Blei, 2019) and related substitute confounder methods exploit this idea, but flexible assignment models can fit the joint distribution of the causes while producing scores that over-encode the treatment vector, collapse overlap, or capture single-cause variation. We develop a Bayesian factor assignment framework for learning sparse substitute confounders that retain coarse multi-cause dependence with shrinkage priors. The theory is stated at the level of posterior concentration, factor score contraction, and overlap-preserving assignment geometry and therefore does not rely on a particular shrinkage prior. Under these conditions, the proposed regression-adjusted estimators are consistent for mean potential outcomes when the corresponding latent variable identification assumptions hold. Shrinkage priors provide a natural tool for latent structural learning: they favour low-dimensional factors supported by multiple causes, discourage effectively single-cause factors, and induce an ordering of the latent factors through progressive shrinkage. Synthetic experiments illustrate the roles of signal strength, outcome validity, and geometry-aware regularization. In an Alzheimer's Disease Neuroimaging Initiative (ADNI) baseline analysis, sparse substitute scores recover much of the adjustment obtained by directly conditioning on invasive cerebrospinal-fluid biomarkers, while collapse diagnostics identify when fitted factors reduce to individual observed measurements.

06.
bioRxiv (Bioinfo) 2026-06-17

DNA-binding specificity recognition from predicted homologous protein-DNA structures

Predicting protein DNA-binding specificity is essential for understanding gene regulation and disease mechanisms. Existing deep learning methods typically infer specificity from a single protein-DNA complex structure, which limits their ability to capture the diverse geometric patterns underlying protein-DNA recognition. Homologous protein-DNA interfaces provide complementary structural evidence and richer geometric features related to interatomic interactions. To address the limited diversity and coverage of experimentally determined complexes, we constructed a large-scale library of predicted homologous protein-DNA complex structures. Building on this resource, we propose HomoDSP, a template-retrieval-based framework for accurate DNA-binding specificity prediction. Benchmark evaluations and validation on newly released JASPAR 2026 samples indicate that HomoDSP outperforms existing methods in both accuracy and generalization, with particularly substantial gains on high-error samples. Moreover, this performance is largely retained when AlphaFold3-predicted complex structures are used as input. Template- and residue-level interpretability analyses suggest that HomoDSP improves prediction by focusing on DNA-affinity residues across multiple homologous templates. Finally, universal Protein Binding Microarrays evaluations on AI-designed DNA-binding proteins show that HomoDSP rescues a baseline failure mode in which the baseline method produces incorrect predictions because of training-set bias. Together, these results support the use of homologous template interfaces as informative structural priors for decoding protein DNA-binding specificity.

07.
arXiv (CS.CV) 2026-06-11

Temporal2Seq: A Unified Framework for Temporal Video Understanding Tasks

With the development of video understanding, there is a proliferation of tasks for clip-level temporal video analysis, including temporal action detection (TAD), temporal action segmentation (TAS), and generic event boundary detection (GEBD). While task-specific video understanding models have exhibited outstanding performance in each task, there remains a dearth of a unified framework capable of simultaneously addressing multiple tasks, which is a promising direction for the next generation of AI. To this end, in this paper, we propose a single unified framework, coined as Temporal2Seq, to formulate the output of these temporal video understanding tasks as a sequence of discrete tokens. With this unified token representation, Temporal2Seq can train a generalist model within a single architecture on different video understanding tasks. In the absence of multi-task learning (MTL) benchmarks, we compile a comprehensive co-training dataset by borrowing the datasets from TAD, TAS, and GEBD tasks. We evaluate our Temporal2Seq generalist model on the corresponding test sets of three tasks, demonstrating that Temporal2Seq can produce reasonable results on various tasks and achieve advantages compared with single-task training on this framework. We also investigate the generalization performance of our generalist model on new datasets from different tasks, which yields superior performance to the specific model.

08.
arXiv (CS.CL) 2026-06-17

Structural Role Injection in Handlebars-Templated LLM Prompts: Triple-Brace Interpolation, Delimiter Family, and the Limits of HTML Auto-Escaping

Large language model applications build prompts from templates, and Handlebars is a widely used templating engine and the default prompt-template format in Microsoft Semantic Kernel. Its double-brace {{x}} expression HTML-escapes the interpolated value and is documented as the safe default; its triple-brace {{{x}}} expression inserts the value raw. We show that this choice silently governs an application's exposure to structural role injection, where attacker-controlled data carries chat role delimiters that forge a higher-privilege turn. A model-free analysis establishes the mechanism: Handlebars escaping rewrites angle brackets but not square brackets, colons, or Markdown hashes, so it neutralises ChatML, Llama-3, and XML role delimiters (survival rate 0.00) while leaving Llama-2 [INST], legacy Human:/Assistant:, and Markdown ### delimiters intact (survival rate 1.00 for the last two). We then run 5760 trials across seven delimiter families, two attack objectives, and four models (GPT-3.5 Turbo, GPT-4o mini, GPT-4.1 mini, Claude Haiku 4.5) at a combined API cost of 1.63 USD. GPT-3.5 Turbo follows the task-hijack instruction in 97% of raw and 91% of escaped trials, with the escaping protection concentrated in the angle-bracket families and absent for the colon- and Markdown-based families; the harder secret-exfiltration objective, which does not saturate, exposes the same family interaction more cleanly. Claude Haiku 4.5 resists both objectives almost entirely. The escaped default protects only the delimiter schemes whose characters HTML escaping happens to cover, gives no protection for the rest, and cannot substitute for a structural separation of instruction and data.

09.
Nature Biotechnology 2026-06-19

Efficient site-specific gene addition using R2 retrotransposons in tobacco and rice

Authors:

Precise integration of multikilobase DNA fragments remains a major technical barrier in plants. Here we introduce non-long terminal repeat (non-LTR) R2 retrotransposons as a versatile system for targeted gene integration in plants. We reconstituted R2 activity in Nicotiana benthamiana and benchmarked insertion efficiency and fidelity using a TMV-based episomal reporter system. We demonstrate site-specific integration of GFP (2.2 kb) and recombinase-compatible landing pads (0.6 kb) into 28S rDNA arrays, with intact cassette insertion frequencies up to 75% and 53%, respectively. To temporally constrain donor availability and avoid DNA intermediates, we combined in planta effector expression with recombinant RNA virus-mediated donor delivery. We apply R2 retrotransposons for targeted insertion of resistance cassettes within the rDNA of rice callus, achieving integration efficiencies up to 17%. These results position R2 retrotransposons as a double-strand break-free system for RNA-templated insertion of multikilobase gene cassettes at rDNA loci, for safe-harbor trait stacking in plants with potential applications in crop improvement and synthetic biology. Retrotransposons are applied in plants for safe-harbor transgene integration.

10.
arXiv (CS.LG) 2026-06-15

On the Influence of the Feature Computation Budget on Per-Instance Algorithm Selection for Black-Box Optimization

arXiv:2605.04954v2 Announce Type: replace-cross Abstract: Per-instance algorithm selection (PIAS) takes advantage of complementarity between a set of algorithms by deciding which algorithm to run on a given instance. This decision is based on features of the instances, which, in the context of black-box optimization (BBO), require a part of the optimization budget to be computed. This raises two questions: (a) from which fraction of the budget spent on feature computation does PIAS become worth it for BBO, and (b) which fraction of the budget optimizes the tradeoff between feature accuracy and PIAS performance. To this end, we perform a broad study where PIAS with varying sampling budgets for feature computation is compared to the single best algorithm on a broad range of algorithm selection scenarios. These scenarios consist of two portfolio sizes, three problem sets, 4 dimensionalities, and 10 target budgets. We find that PIAS is viable for the majority of tested scenarios, even when as much as a quarter of the total budget is spent on feature computation. The tradeoff for the fraction of the budget spent on feature computation to maximize the benefit of PIAS is highly dependent on the specific AS scenario. Further, on average 20 percent of PIAS loss to the virtual best solver is explained by the budget spent on feature computation, highlighting the importance of properly accounting for the feature budget.

11.
arXiv (CS.LG) 2026-06-18

Generalised Eigenvalue Geometry of Semantic Adversarial Attacks

arXiv:2606.19212v1 Announce Type: cross Abstract: Recent empirical work shows that semantically equivalent paraphrases can fool financial sentiment classifiers: although a paraphrase remains close to the original under a strong reference embedding, it may shift the target model's representation enough to change the predicted class. Existing robustness theory either assumes a single-model threat model or focuses mainly on empirical attack algorithms. We develop a continuous local model of semantic paraphrase perturbations that captures this two-model structure. We show that the worst-case local displacement of the target representation, subject to a proxy-model budget, is governed by the largest generalised eigenvalue of a matrix pencil $(A,B)$ constructed from the Jacobians of the two embedding maps. The resulting attackability index $\lambda^*(x)$ is intrinsic to the local paraphrase geometry and the chosen embedders, yields a closed-form prediction-flip condition for affine readouts, and supports conservative population and finite-sample attackability certificates. For uniform control over classes of affine readouts, we derive a distribution-free VC bound for binary attackability indicators and a scale-sensitive margin bound based on an attackability-adjusted margin that subtracts a local geometric penalty from the standard classifier margin. We also connect the continuous theory to discrete paraphrase search, identify an asymmetry between successful and unsuccessful finite searches, and give a covering condition under which the discrete and continuous settings agree. Finally, we propose an empirical verification framework using soft-token relaxations and generated paraphrase sets to assess the local eigenvalue geometry, prediction-flip condition, and finite-search approximation on a deployed financial-text classifier.

12.
arXiv (CS.CL) 2026-06-16

The BD-LSC Dataset: Facilitating the Benchmarking of Models for Lexical Semantic Change Detection in Slang and Standard Usage

Automatic semantic change detection aims to identify how word meanings shift over time, offering insights into both linguistic and societal change. Despite recent progress in computational lexical semantic change (LSC), existing benchmarks and methods struggle to capture bi-directional semantic change, particularly cases where words simultaneously gain and lose senses. This problem is especially challenging for words that have both slang and standard meanings. To address these gaps, we introduce two complementary benchmark datasets. The Bi-Directional Lexical Semantic Change (BD-LSC) dataset captures sense gain, sense loss, and stability across three time periods, enabling the study of complex semantic trajectories. The SlangTrack Word Sense Disambiguation (ST-WSD) dataset provides fine-grained, instance-level sense annotations for words combining slang and standard usages, supporting systematic benchmarking of WSD and semantic change detection models. Using these benchmarks, we systematically evaluate models across different methodological families: unsupervised clustering using contextualised embeddings, supervised machine learning, transformer-based models, and state-of-the-art large language models. Among the evaluated systems, the few-shot GPT-4o model achieved the strongest aggregate performance on Exact Sense Match (ESM) and multi-label accuracy; however, Macro-F1 scores near 0.5 across all systems show that rare slang senses remain difficult, which we identify as the central open challenge.

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

Judging Against the Reference: Uncovering Knowledge-Driven Failures in LLM-Judges on QA Evaluation

While large language models (LLMs) are increasingly used as automatic judges for question answering (QA) and other reference-conditioned evaluation tasks, little is known about their ability to adhere to a provided reference. We identify a critical failure mode of such reference-based LLM QA evaluation: when the provided reference conflicts with the judge model's parametric knowledge, the resulting scores become unreliable, substantially degrading evaluation fidelity. To study this phenomenon systematically, we introduce a controlled swapped-reference QA framework that induces reference-belief conflicts. Specifically, we replace the reference answer with an incorrect entity and construct diverse pairings of original and swapped references with correspondingly aligned candidate answers. Surprisingly, grading reliability drops sharply under swapped references across a broad set of judge models. We empirically show that this vulnerability is driven by judges' over-reliance on parametric knowledge, leading judges to disregard the given reference under conflict. Finally, we find that this failure persists under common prompt-based mitigation strategies, highlighting a fundamental limitation of LLM-as-a-judge evaluation and motivating reference-based protocols that enforce stronger adherence to the provided reference.

14.
arXiv (CS.LG) 2026-06-16

IBAD: Interpretable Behavioral Anomaly Detection on Human Mobility Data

arXiv:2606.16023v1 Announce Type: new Abstract: Human mobility appears highly diverse, yet much of a person's daily mobility can be explained by a small set of recurring behavioral templates, such as commuting, school-centered activities, caregiving, nightlife, or errand patterns. We present \texttt{IBAD} (\underline{I}nterpretable \underline{B}ehavioral \underline{A}nomaly \underline{D}etection), a framework that learns interpretable daily mobility templates and represents each individual as a distribution over mixtures of these templates. Rather than focusing on specific locations, IBAD characterizes activities that individuals perform across locations. This approach first discovers global behavioral templates using Latent Dirichlet Allocation (LDA), then employs a hierarchical self-supervised model to learn normal behavior of individuals from their soft behavioral templates. We also introduce a splicing benchmark that creates controlled behavioral mismatches between an individual's historical profile and injected mobility patterns. Experiments on real-world and synthetic datasets show that daily behavior can be effectively decomposed into a small number of interpretable templates. Crucially, we show that the learned behavioral archetypes transfer across distinct geographic and demographic contexts. Furthermore, IBAD maintains a robust competitive performance across all settings. For reproducibility purposes, the code is accessible at ~\href{https://github.com/USC-InfoLab/IBAD}{https://github.com/USC-InfoLab/IBAD}.

15.
arXiv (CS.CL) 2026-06-16

Revisiting the Systematicity in Negation in the Era of In-Context Learning

Understanding the meaning of negated sentences remains one of the challenges for language models, even in the era of large language models (LLMs). We analyze systematicity regarding LLM understanding of negation from two perspectives: behavioral systematicity and representational systematicity. For behavioral systematicity, we confirm that through demonstrations and in-context learning, LLMs can recognize negation expressions and scope within sentences to some extent, but they fail to achieve perfect performance. In particular, the difficulty of the negation scope recognition for models varies depending on the output format. For representational systematicity, we analyze the extent to which function vectors can be robustly constructed from in-context examples for tasks that are essential to understanding negation. The experiments suggest that while function vectors can be composed for negation cue extraction tasks, extracting function vectors for recognizing scope is more challenging.

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

DDTNet: Degradation Disentanglement and Transfer Network for Test-Time All-in-One De-weathering Adaptation

All-in-one adverse weather image restoration aims to remove multiple degradations, such as rain, haze, and snow, using a single unified model. Despite their broad applicability, existing methods typically compromise performance, delivering balanced but suboptimal results for individual degradation types. This issue becomes more pronounced when a domain gap exists between training and testing data. Motivated by the observation that modeling degradation patterns is more feasible than recovering clean content, we propose the Degradation Disentanglement and Transfer Network (DDTNet), which focuses specifically on degradation transfer. By disentangling degradation patterns from target-domain degraded images and transferring them to source domain clean images, DDTNet generates domain-adaptive paired training data. These pairs are then used to fine-tune restoration models, significantly enhancing their adaptability across diverse weather conditions and domains. The core of DDTNet is the Degradation Disentanglement Module (DDM), which comprises Degradation Coupled Attention (DCA) to capture both general and weather-specific features, thereby enabling effective disentanglement and transfer of degradation patterns. Experimental results demonstrate that DDTNet significantly and consistently improves existing all-in-one models across real-world deraining, desnowing, and dehazing datasets.

17.
medRxiv (Medicine) 2026-06-22

Why drinking episodes escalate differently: Event-level pathways linking hazardous alcohol consumption and sexual risk

Background: Alcohol-involved drinking episodes vary in whether they involve hazardous alcohol consumption alone, near-miss sexual risk, or sexual risk behavior, but the within-event mechanisms underlying this variability remain unclear. Methods: Guided by syndemic theory, we conducted a qualitative event-level analysis using modified grounded theory among adults in the San Francisco Bay Area who reported hazardous alcohol consumption, defined as an Alcohol Use Disorder Identification Test score [&ge;]16. In-depth interviews elicited narratives of recent heavy drinking episodes and yielded 64 discrete drinking events across 22 participants. We focused on 35 events with evidence of within-event interaction between biopsychosocial and contextual factors. Using constant comparison, we identified escalation pathways, characterized interruption, and examined how events diverge into three outcomes: hazardous alcohol consumption only, hazardous alcohol consumption with near-miss sexual risk (when risk was plausible but not enacted), and hazardous alcohol consumption with sexual risk behavior. Results: Two primary escalation pathways emerged. Dose-driven escalation involved cumulative alcohol or substance exposure that progressively impaired awareness and self-regulation. Meaning-driven escalation involved prioritizing connection, intimacy, or belonging despite awareness of risk. Time-driven continuation extended exposure across contexts and amplified both pathways. Hazardous alcohol consumption-only events more often followed dose-driven pathways, whereas events involving sexual risk behavior more often followed meaning-driven pathways. Near-miss events occurred across both pathways and illustrated how interruption before the escalation constraint point, when the capacity to modify behavior became reduced, could redirect escalation before sexual risk behavior occurred. Across events with similar levels of intoxication narratives, outcomes diverged according to when the interruption occurred and whether it altered escalation. Conclusion: Hazardous drinking episodes diverge into different outcomes based on escalation pathways and the timing and effectiveness of interruption. Early and effective interruption before the escalation constraint point may represent a key target for harm-reduction strategies to prevent progression to sexual risk behavior.

18.
medRxiv (Medicine) 2026-06-16

Daily Healthy Eating Index (HEI-2020) scoring reveals diet quality patterns masked by aggregation

The Healthy Eating Index (HEI-2020) is conventionally computed by aggregating intake across days before scoring. Digital food logging enables an alternative: scoring each day and averaging daily scores. These methods are not equivalent. The HEI's density-based structure and component caps cause aggregation to inflate adequacy scores when intake is irregular. Using Food & You data, we show daily HEI correlates more strongly with microbiome diversity, and recommend co-reporting both metrics.

19.
bioRxiv (Bioinfo) 2026-06-12

The Geometry of Allostery: A Laplacian Minor Hierarchy for Many-Body Protein Communication

Quantifying how cooperative, many-body relationships drive allostery in protein networks remains a major challenge. To address this, we develop the Laplacian minor hierarchy, a mathematical framework that characterizes the geometric invariants of a protein network. Lower-order minors yield standard metrics including the partition function and effective distances, whereas higher-order minors define novel topological measures: cooperation indices, each bounded between zero and one, that characterize pathway correlations at increasing levels of complexity, the third-order minor determines whether allosteric pathways are correlated or uncorrelated, and the fourth-order minor quantifies how distinct pathways communicate through intermediary residues. We apply this framework to analyze the evolutionary adaptation of the PSD95pdz3 domain from Class I to Class II ligand specificity via mutations G330T and H372A. The cooperation index demonstrates a distinct evolutionary hierarchy: the G330T mutation establishes distributed pathway couplings that the H372A mutation subsequently exploits, whereas H372A alone produces minimal global changes. Furthermore, the fourth-order analysis identifies His317 as a critical intermediary node bridging the class-switching (330-372) and class-bridging (330-400) allosteric pathways. These results demonstrate that allosteric dependencies emerge only when mutations accumulate in specific combinations, with a hierarchical organization of pathways structured around position 330 and intermediary nodes His317 and Phe400. Rather than predicting allosteric mechanisms, this framework provides a mechanistic explanation for why and how allostery emerges during protein evolution.

20.
arXiv (CS.AI) 2026-06-12

scLLM-DSC: LLM-Knowledge Enhanced Cross-Modal Deep Structural Clustering for Single-Cell RNA Sequencing

arXiv:2606.13007v1 Announce Type: cross Abstract: Clustering is fundamental to scRNA-seq analysis, serving as a cornerstone for identifying cell populations and resolving tissue heterogeneity. However, existing methods focus on mining numerical statistical patterns, suffering from semantic agnosticism by neglecting the intrinsic biological functions encoded by genes. While Large Language Models (LLMs) offer promising semantic capabilities, their direct adaptation to cell clustering is hindered by the structural mismatch between generative pre-training objectives and discriminative downstream tasks. To bridge this gap, we propose scLLM-DSC, a novel LLM-Knowledge Enhanced Cross-Modal Deep Structural Clustering framework. Diverging from data-driven paradigms, scLLM-DSC establishes a semantically-grounded representation by synergizing two views: a Knowledge-Driven Semantic View derived from NCBI gene priors and contextualized Cell2Sentence embeddings, and a Structure-Aware Topological View extracted via a graph-guided encoder. Crucially, we introduce a cross-modal contrastive alignment mechanism to enforce consistency between biological semantics and transcriptomic features within a unified latent space. Extensive benchmarks demonstrate that scLLM-DSC significantly outperforms eleven state-of-the-art baselines in clustering accuracy.

21.
arXiv (CS.CL) 2026-06-11

The Language You Ask In: Language-Conditioned Ideological Divergence in LLM Analysis of Contested Political Documents

Authors:

Large language models (LLMs) are increasingly deployed as analytical tools across multilingual contexts, yet their outputs may carry systematic biases conditioned by the language of the prompt. This study presents an experimental comparison of LLM-generated political analyses of a Ukrainian civil society document, using semantically equivalent prompts in Russian and Ukrainian administered to two frontier models from different developers, ChatGPT 5.2 and Claude Opus 4.5. Despite identical source material and parallel query structures, both models diverged along the same axis: Russian-language outputs leaned toward delegitimizing framings, characterizing civil society actors as externally funded elites constraining a democratic mandate, while Ukrainian-language outputs treated the same actors as legitimate stakeholders in democratic contestation. The magnitude of this divergence, however, was model-dependent. ChatGPT's Russian output reproduced vocabulary characteristic of Russian state discourse; Claude Opus's stayed in a mainstream critical idiom and hedged its judgments in both languages. These findings demonstrate that prompt language alone can systematically shift the ideological orientation of an unchanged model analyzing identical content. The shift is a general property of multilingual LLMs whose severity, and whose alignment with propaganda narratives, varies across systems. The implications reach AI deployment in polarized information environments, cross-lingual research, and AI governance in multilingual societies.

22.
arXiv (CS.LG) 2026-06-19

Learning to Emulate Chaos: Adversarial Optimal Transport Regularization

arXiv:2604.21097v2 Announce Type: replace-cross Abstract: Chaos arises in many complex dynamical systems, from weather to power grids, but is difficult to accurately model with data-driven methods such as machine learning emulators. While emulators are promising tools for accelerating simulations and solving inverse problems, they still struggle to learn chaotic dynamics, where sensitivity to initial conditions renders exact long-term forecasts infeasible, especially given noisy data. Recent work instead trains emulators to match the statistical properties of chaotic attractors, but these approaches often rely on handcrafted summary statistics or large, diverse multi-environment datasets. In this work, we propose a family of adversarial optimal transport objectives that can jointly learn high-quality summary statistics and a physically consistent emulator from a single noisy trajectory. We theoretically analyze and experimentally validate a Sinkhorn divergence formulation (2-Wasserstein) and a WGAN-style dual formulation (1-Wasserstein) of our approach. Numerical experiments across a variety of chaotic systems, including ones with high-dimensional spatiotemporal chaos, show that emulators trained using our proposed objectives have significantly improved long-term statistical fidelity.

23.
medRxiv (Medicine) 2026-06-19

A soluble bi-specific fusion protein for the improved expansion of human CD8+ CAR-T cells

The success of Chimeric Antigen Receptor (CAR) T cell therapy is heavily dependent on the quality of the final cellular product. Current expansion protocols often rely on reagents that require removal from cell culture media, posing logistical challenges in manufacturing, and can also lead to terminal differentiation. Here, we evaluate the use of a soluble, bead-free T cell activator, T cell expansion protein (T-CEP), as a streamlined alternative for generating potent CAR-T cells. Human T cells were activated with T-CEP or known T cell activators (Dynabeads and TransAct) and transduced with either CD19 or interleukin-13 (IL-13) mutein (tetravariant-13; TV-13)-based CAR lentiviral vectors. Our results demonstrate that T-CEP supports robust CAR-T cell expansion and achieves transduction efficiencies comparable to commercial reagents for both types of CAR-T cells. Notably, T-CEP significantly favored the expansion of CD8+ T cells, yielding an enhanced CD27+ phenotype and a lower CD4:CD8 ratio compared to TransAct. Cytotoxicity assays confirmed that T-CEP-expanded CAR-T cells possess cytolytic function equivalent to commercial reagents for both CARs, while exhibiting lower levels of inflammatory cytokine secretion. In summary, T-CEP represents a competitive alternative to existing expansion agents, as it does not require its removal during CAR-T manufacturing and generates a CD8+ dominant, less-differentiated phenotype without compromising efficacy.

24.
arXiv (CS.CV) 2026-06-12

MaskWAM: Unifying Mask Prompting and Prediction for World-Action Models

World Action Models (WAMs) present a promising paradigm for robotic control via video prediction. However, current WAMs suffer from fundamental spatial bottlenecks: standard text inputs introduce referential ambiguity in cluttered scenes, while unstructured RGB predictions lack semantic grounding and remain biased by task-irrelevant backgrounds. To overcome these limitations, we introduce MaskWAM, an object-centric world-action model. By jointly integrating masks as both explicit inputs and predictions via a unified Mixture of Transformers (MoT), MaskWAM unlocks robust policy generalization. This design provides two key benefits: (1) predicting future masks yields object-centric semantic supervision that suppresses visual noise, significantly enhancing even standard text-conditioned WAMs; and (2) coupling this predictive supervision with first-frame visual prompts, such as target object masks, establishes a precise spatial anchor that substantially reduces language ambiguity. Crucially, as WAMs are inherently vision-driven architectures, direct mask conditioning yields substantially stronger guidance than text alone, establishing a precise and robust paradigm for manipulating unseen objects. Evaluations on LIBERO, RoboTwin, and real-world tasks demonstrate that MaskWAM significantly outperforms baselines in both language-clear and language-ambiguous tasks.

25.
arXiv (CS.CL) 2026-06-12

NaturalFlow: Reducing Disruptive Pauses for Natural Speech Flow in Simultaneous Speech-to-Speech Translation

Simultaneous speech-to-speech translation aims to enable near-real-time communication by minimizing latency, offering a compelling, real-time alternative to the high latency of consecutive translation. However, the excessive pursuit of low latency often results in fragmented chunk-wise speech. Consequently, listeners are subjected to an unnatural acoustic flow punctuated by frequent pauses, which could increase their cognitive load. To bridge this gap, we introduce a fluency-aware optimization framework designed to discover the sweet spot between the low-latency benefits of simultaneous translation and the natural flow of consecutive translation. Our framework minimizes inter-chunk silences by leveraging model-internal signals, including linguistic diversity and induced temporal variability in speech durations. Experiments on short- and long-form benchmarks show that our framework produces natural speech flow while maintaining competitive latency and translation quality.