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01.
arXiv (CS.CV) 2026-06-17

Recover Semantics First, Generate Better: Improved Latent Modeling for 3D MRI Reconstruction and Cross-Contrast Synthesis

Multi-contrast magnetic resonance imaging (MRI) provides complementary information for clinical diagnosis. However, acquiring all MRI sequences is often time-consuming and costly. Recent generative models perform cross-contrast synthesis to address this issue by inferring absent contrasts from the available ones. Nevertheless, synthesizing 3D MRI presents significant challenges. Due to the massive volume sizes, operating directly in the pixel space is computationally prohibitive; therefore, a common approach is to first compress the 3D volumes into a latent space and subsequently train generative models in that space. We observe that existing compression architectures face several critical issues: they under-preserve long-range anatomical coherence, discard clinically meaningful semantics, and rely on optimization objectives that lead to over-smoothed reconstructions. Ultimately, these shortcomings compromise the performance of subsequent generative models. In this work, we propose a semantics-first latent modeling framework for 3D MRI reconstruction and cross-contrast synthesis. Specifically, we introduce a Latent Harmonization Encoder (LHE) to capture global anatomical dependencies, ensuring coherent volumetric representations. To mitigate semantic degradation during latent compression, we further design a Semantic Recovery Block (SRB) that injects high-level priors from a self-supervised semantic teacher, enhancing contrast-aware separability in the latent space. Additionally, we propose an Anatomy-aware Frequency Loss (AFL) to adaptively preserve diagnostically relevant high-frequency structures. Extensive experiments on two public multi-contrast MRI datasets demonstrate consistent improvements in reconstruction fidelity and cross-contrast synthesis quality. Our code is available at https://github.com/script-Yang/RSF.

02.
arXiv (CS.CL) 2026-06-11

Self-Attention as Transport: Limits of Symmetric Spectral Diagnostics

When a language model processes a hallucinated response, its attention routing tends to fail in one of two shapes: over-concentrating on a narrow set of positions, or spreading so diffusely that relevance is diluted, and the shape of the failure carries diagnostic signal. We study these shapes as a diagnostic characterization, computed from attention matrices under forced scoring of benchmark-labeled responses rather than during live generation. A widely used family of spectral methods analyzes the symmetric component of the degree-normalized attention operator, which governs transport capacity; we prove that every transpose-invariant spectral diagnostic of this operator is structurally orientation-blind (it cannot distinguish an operator from its transpose, and therefore cannot detect information-flow direction), with a converse to the blindness theorem bounding any Lipschitz diagnostic's transpose sensitivity by the asymmetry coefficient $G$. Pairing this with a closed-form bipartite-Cheeger landscape for canonical causal architectures, we show that uniform causal attention satisfies an $n$-independent floor $\phi \ge 1/5$, while window attention pierces the floor as $O(w/n)$; failure modes are shape-different, not just value-different. This floor is an idealized-architecture benchmark, not an empirical attractor: the fraction of real attention heads that pierce it is itself an architectural signature. The resulting two-axis diagnostic ($\phi$ for capacity, $G$ for direction) yields a falsifiable polarity prediction: bottleneck- and diffuse-dominated benchmarks should exhibit opposite polarity. Under length-controlled evaluation, transport features retain interpretable signal (0.62-0.84 LC-AUROC) across the tested decoder-only, encoder-only, and encoder-decoder models, with polarity reversing as predicted between HaluEval and MedHallu.

03.
arXiv (CS.AI) 2026-06-25

When Multi-Sensor Fusion Fails to Generalize: Cattle Posture Classification Under Animal-Level and Temporal Distribution Shift

arXiv:2606.24986v1 Announce Type: cross Abstract: Automated cattle posture-classification systems frequently report near-perfect accuracy, yet their robustness under realistic deployment conditions remains largely unknown. In particular, it is unclear whether multimodal sensor fusion improves generalisation or leads models to rely on context-specific signals that fail under distribution shift. Here, we evaluate the robustness of automated posture classification (lying versus standing) using collar accelerometers, rumen-bolus sensors, and environmental measurements collected from a pasture-based beef cattle herd across two consecutive years (2024-2025). XGBoost served as the primary model, with Logistic Regression, Random Forest, and Long Short-Term Memory networks evaluated as comparative baselines. Model robustness was assessed under progressively more stringent evaluation protocols, ranging from conventional random train-test splits to leave-one-animal-out validation and cross-year evaluation on an independent cohort of previously unseen animals recorded one year later. While multimodal models achieved strong within-year performance (macro-F1 0.94), the performance declined substantially under cross-year evaluation (macro-F1 0.49). Explainability analysis revealed persistent reliance on rumen-bolus activity and environmental variables even when predictive performance deteriorated. Distribution-shift diagnostics further confirmed substantial differences in feature distributions between recording years. Our findings demonstrate that commonly used evaluation protocols can substantially overestimate real-world performance and that multimodal sensor fusion may reduce, rather than improve, robustness under temporal distribution shift. More broadly, the results highlight that benchmark accuracy alone is insufficient to assess deployment readiness and underscore the need for robustness-centred evaluation in livestock-monitoring research.

04.
arXiv (CS.CL) 2026-06-18

TopBench: A Benchmark for Implicit Predictive Reasoning in Tabular Question Answering

Large Language Models (LLMs) have advanced Table Question Answering, where most queries can be answered by extracting information or simple aggregation. However, a common class of real-world queries is implicitly predictive, requiring the inference of unobserved answers from historical patterns rather than mere retrieval. These queries introduce two challenges: recognizing latent intent and reliable predictive reasoning over massive tables. To assess LLMs in such Tabular questiOn answering with implicit Prediction tasks, we introduce TopBench, a benchmark consisting of 779 samples across four sub-tasks, ranging from single-point prediction to decision making, treatment effect analysis, and complex filtering, requiring models to generate outputs spanning reasoning text and structured tables. We evaluate diverse models under both text-based and agentic workflows. Experiments reveal that current models often struggle with intent recognition, defaulting to just lookups. Deeper analysis identifies that accurate intent disambiguation serves as the prerequisite for leading these predictive behaviors. Furthermore, elevating the upper bound of prediction precision requires the integration of more sophisticated modeling or reasoning capabilities.

05.
arXiv (CS.LG) 2026-06-25

Limitations of SGD for Multi-Index Models Beyond Statistical Queries

arXiv:2602.05704v2 Announce Type: replace Abstract: Understanding the limitations of gradient methods, and stochastic gradient descent (SGD) in particular, is a central challenge in learning theory. To that end, a commonly used tool is the Statistical Queries (SQ) framework, which studies performance limits of algorithms based on noisy interaction with the data. However, it is known that the formal connection between the SQ framework and SGD is tenuous: Existing results typically rely on adversarial or specially-structured gradient noise that does not reflect the noise in standard SGD, and (as we point out here) can sometimes lead to incorrect predictions. Moreover, many analyses of SGD for challenging problems rely on non-trivial algorithmic modifications, such as restricting the SGD trajectory to the sphere or using very small learning rates. To address these shortcomings, we develop a new, non-SQ framework to study the limitations of standard vanilla SGD, for single-index and multi-index models (namely, when the target function depends on a low-dimensional projection of the inputs). Our results apply to a broad class of settings and architectures, including (potentially deep) neural networks.

06.
arXiv (CS.AI) 2026-06-19

FlowFake: Liquid Networks for Audio Deepfake Detection

arXiv:2606.19579v1 Announce Type: cross Abstract: Audio deepfakes generated by neural text-to-speech and voice-cloning systems threaten speaker verification and public discourse at scale. The core challenge is cross-dataset generalization: detectors trained on one synthesis pipeline collapse on unseen forgeries. We argue that this failure is primarily because of structural synthetic speech artifacts which are multi-timescale trajectory anomalies. Though every existing detector aggregates a fixed-window frame statistics, this misaligns the architecture with the signal. We propose FlowFake, a Liquid Time-Constant (LTC) architecture whose hidden state evolves via a learned ODE, with per-neuron adaptive time constants simultaneously resolving spectral (10ms) and prosodic (2s) cues. At only 34K parameters FlowFake achieves formal BIBO stability and O(dt^4) integration error. On a four-dataset cross domain benchmark (ASVspoof2019-LA, FakeOrReal, InTheWild, MLAAD), FlowFake reaches 75.29% on ASVspoof2019 trained only on FakeOrReal and 79.97% trained only on MLAAD. It outperforms RawGAT-ST and Whisper-DF on every evaluated pair and matching SSL Wav2vec2 (300x larger) at 0.01% of its parameter count. The source code is available on : https://github.com/GhostRider2023/FlowFake

07.
arXiv (CS.AI) 2026-06-24

Navigating User Behavior toward Personalized Multimodal Generation

arXiv:2606.24196v1 Announce Type: new Abstract: Modern AIGC pipelines deliver high-fidelity images and videos but presuppose a well-formed creation instruction, while end users rarely articulate visual details, leaving generators misaligned with user demand. We study personalized content generation, which turns a user's interaction history into an executable instruction for downstream synthesis, and identify two obstacles: behavior must be encoded in a form legible to language reasoning, and the model must acquire instruction-writing skill absent from both pretraining and behavior data. We propose NaviGen, which represents each item with a dual identifier coupling a collaborative code and a textual code as a behavioral substrate and a semantic bridge in one token stream. On this representation, a two-stage SFT+RL pipeline first distills preference reasoning and instruction writing from evolutionarily searched supervision, then aligns generation with user intent through hierarchical and self-consistent rewards. Experiments across product, game, and short-video domains show that NaviGen improves personalized image and video generation, strengthens next-item prediction, and yields more specific, relevant, and visually generatable instructions. Our code is anonymously released at: https://github.com/iLearn-Lab/NaviGen.

08.
arXiv (quant-ph) 2026-06-11

Raw-Curve Quantum Fingerprints: A Mahalanobis Authentication Framework with Drift Early Warning and Adversarial Detection

arXiv:2606.11644v1 Announce Type: new Abstract: Quantum cloud platforms are poised to deliver powerful computing capabilities, but users have no direct means to verify which physical device executes their workload. This lack of transparency enables hardware substitution attacks, where a malicious adversary could redirect a job to a substituted or inferior processor. We present a general authentication framework that addresses this problem by constructing multi-dimensional quantum fingerprints from raw measurement data. Without any curve fitting, we directly concatenate the raw statistics of complementary experiments into a high-dimensional feature vector that preserves subtle device-specific information. A Mahalanobis nearest-neighbor classifier achieves 100\% benign authentication accuracy on three superconducting processors over a three-week chronological split. The classifier naturally yields an authentication confidence $C_{\mathrm{claimed}}$ which reveals device-specific safety margins and motivates per-device alert thresholds. We assess the framework's robustness under two distinct scenarios. Under additive isotropic Gaussian noise, $C_{\mathrm{claimed}}$ decays predictably at a rate explained by inverse covariance traces, enabling an early warning mechanism. Against white-box adversarial perturbations, the same confidence threshold detects $L_2$ targeted attacks with near-perfect success and reveals device-dependent empirical thresholds for $L_\infty$ attacks, while untargeted and sparse attacks are ineffective. The proposed framework thus unifies fingerprint extraction, drift-resilient authentication, proactive health monitoring, and adversarial defense, offering a practical step toward trustworthy quantum cloud computing.

09.
arXiv (math.PR) 2026-06-17

Analysis of the asymmetric shelf shuffle

arXiv:2606.18047v1 Announce Type: new Abstract: In an asymmetric shelf shuffle, a deck of $n$ cards is dealt sequentially from the bottom and assigned one of the $m$ shelves uniformly at random. The card is placed at the top of the assigned shelf with probability $p$, and at the bottom of the assigned shelf with probability $(1-p)$. Analysis of the shelf shuffle has gained much attention recently, and the case $p=1/2$ was first treated by Diaconis–Fulman–Holmes [Ann. Appl. Prob. 23 (2013), no. 4, 1692–1720]. In this paper, we extend the analysis of the shelf shuffle to general $p\in (0, 1)$. In particular, we study the distribution of cycles, cycle lengths, number of descents, number of valleys, number of inversions, and the RSK shape of a permutation obtained from an asymmetric shelf shuffle. Our results extend the analysis of Diaconis–Fulman–Holmes to arbitrary $p$. Furthermore, our analysis of the distribution of descents and inversions is new even for $p=1/2$.

10.
arXiv (CS.CV) 2026-06-19

Timage: A Generative Text-in-Image Paradigm for Fine-Tuning Vision-Language Models

Multimodal Large Language Models (MLLMs) often lose track of the right image regions during fine-grained spatial reasoning, because a textual query rarely carries any explicit geometric anchor into the pixel domain. Prevailing remedies either rewire the model's weights or pad the prompt with verbose instructions, yet neither reliably pins the language to the correct visual coordinates without eroding the backbone's general competence. We introduce Timage, a paradigm that recasts multimodal understanding as an alignment problem solved at the input: the query is drawn, as a typeset overlay, onto the image itself. The placement and appearance of this overlay are produced by a Constrained Schrödinger Bridge (cSB), an entropic optimal-transport sampler that factorizes layout synthesis into two coupled stochastic stages. The first stage, Region Search, transports noise toward query-aligned image zones while obeying a hard occlusion barrier that protects salient foreground content; the second stage, Appearance Shaping, sizes the glyphs through an ``ink-budget'' regularizer so that the rendered text stays legible and visually balanced. The resulting overlay behaves as an explicit attention beacon that channels the model's focus along spatial semantics. On the VMCBench suite, Timage paired with a modest 7B backbone clearly overtakes far larger proprietary systems as well as parameter-tuned baselines. The study positions deliberate input reconstruction as a powerful, architecture-neutral lever for strengthening multimodal reasoning.

11.
arXiv (math.PR) 2026-06-17

Absolute continuity, supports and idempotent splitting in categorical probability

arXiv:2308.00651v5 Announce Type: replace Abstract: Markov categories have recently turned out to be a powerful high-level framework for probability and statistics. They accommodate purely categorical definitions of notions like conditional probability and almost sure equality, as well as proofs of fundamental results such as the Hewitt–Savage 0/1 Law, the de Finetti Theorem and the Ergodic Decomposition Theorem. In this work, we develop additional relevant notions from probability theory in the setting of Markov categories. This comprises improved versions of previously introduced definitions of absolute continuity and supports, as well as a detailed study of idempotents and idempotent splitting in Markov categories. Our main result on idempotent splitting is that every idempotent measurable Markov kernel between standard Borel spaces splits across another standard Borel space, and we derive this as an instance of a general categorical criterion for idempotent splitting in Markov categories.

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

Misinformation Propagation in Benign Multi-Agent Systems

Multi-agent systems, in which multiple large language model agents solve problems through turn-based interaction, are increasingly deployed in high-stakes settings such as medical diagnosis, legal analysis, and forensic decision-making. Their reliability can be at risk when single agents reason from incorrect or misleading context, e.g., from tool calls, since errors may propagate through agent interactions. This work studies this risk by injecting intent-based misinformation into benign single-agent and multi-agent systems across reasoning, knowledge, and alignment tasks. We find that misinformation can degrade single-agent performance and persists across multi-agent debate, with agents often retaining answers introduced by misinformed peers. Nevertheless, multi-agent debate reduces the resulting performance degradation compared to single-agent prompting, especially when most agents are not exposed to misinformation. Robustness depends on group composition and decision protocol. Consensus can be more stable than voting under peer pressure, while majorities can often steer misinformed agents back toward correct answers. Our results show that misinformation robustness in multi-agent systems depends on the underlying model and also on how agents exchange information and aggregate decisions.

13.
arXiv (CS.LG) 2026-06-16

Formalizing and Mitigating Structural Distortion in LLM Attention for Zero-Shot Graph Reasoning

arXiv:2606.15633v1 Announce Type: new Abstract: Large Language Models (LLMs) have shown promise for reasoning over Text-Attributed Graphs (TAGs). However, applying LLMs to graphs requires linearizing their structure into sequences, introducing distortion rooted in the graph bandwidth problem. While this distortion has been shown to degrade performance, it is often attributed to prompt design or model scale, leaving the underlying mechanism unclear. In this work, we show how rotary positional embeddings turn graph linearization into bandwidth-dependent attention decay, suppressing attention between graph-adjacent nodes that are forced far apart in the serialized sequence. This shifts the focus of LLM-based graph reasoning from prompt engineering and scaling toward correcting attention misalignment. Motivated by this analysis, we propose Graph-aligned Language Attention (GaLA), a lightweight, inference-time modification for LLMs. GaLA biases attention toward graph-adjacent nodes while preserving the LLM's sequential inductive biases. Across TAG benchmarks, GaLA improves performance with negligible overhead, demonstrating that distortion is a correctable bottleneck in LLM-based graph reasoning.

14.
arXiv (CS.AI) 2026-06-12

FinSTaR: Towards Financial Reasoning with Time Series Reasoning Models

arXiv:2605.03460v3 Announce Type: replace Abstract: Time series (TS) reasoning models (TSRMs) have shown promising capabilities in general domains, yet they consistently fail in the financial domain, which exhibits unique characteristics. We propose a general 2 x 2 capability taxonomy for TSRMs by crossing 1) single-entity vs. multi-entity analysis with 2) assessment of the current state vs. prediction of future behavior. We instantiate this taxonomy in the financial domain-where the distinction between deterministic assessment and stochastic prediction is particularly critical-as ten financial reasoning tasks, forming the FinTSR-Bench benchmark based on S&P stocks. To this end, we propose FinSTaR (Financial Time Series Thinking and Reasoning), trained on FinTSR-Bench with distinct chain-of-thought (CoT) strategies tailored to each category. For assessment, which is deterministic (i.e., computable from observable data), we employ Compute-in-CoT, a programmatic CoT that enables models to derive answers directly from raw prices. For prediction, which is inherently stochastic (i.e., subject to unobservable factors), we adopt Scenario-Aware CoT, which generates diverse scenarios before making a judgment, mirroring how financial analysts reason under uncertainty. The proposed method achieves 78.9% average accuracy on FinTSR-Bench, substantially outperforming LLM and TSRM baselines. Furthermore, we show that the four capability categories are complementary and mutually reinforcing through joint training, and that Scenario-Aware CoT consistently improves prediction accuracy over standard CoT. Code is available at https://github.com/seunghan96/FinSTaR.

15.
arXiv (CS.CV) 2026-06-19

Vision-Reasoning-Guided Occlusion Removal from Light Fields

Occlusion-robust scene recovery remains a major challenge in computational imaging, particularly in natural environments where dense foreground vegetation severely limits visibility. We propose a vision-reasoning-guided light field occlusion removal framework that combines the visibility recovery capability of light field integration (LFI) with the semantic reasoning capacity of vision-language models (VLMs). Multi-view observations are first integrated via LFI to suppress foreground occlusions and produce an initial visibility-enhanced representation. A VLM is then incorporated as a conditional semantic prior to restore degraded structures and recover fine details, guided by the observed measurements. To improve recovery consistency and reduce hallucination artifacts, we introduce a multi-sample fusion strategy that aggregates multiple generated hypotheses into a unified estimate. Experimental results on synthetic and real-world datasets demonstrate state-of-the-art performance, achieving the highest average SSIM across four synthetic light field benchmark scenes (4-Syn) and strong generalization across structured and unstructured acquisition settings. These results highlight the effectiveness of combining physical imaging constraints with vision-language reasoning for robust perception under severe occlusion, with applicability to search-and-rescue and exploratory robotic navigation.

16.
arXiv (CS.LG) 2026-06-11

Persistent Homology as a Theory of Emergent Structure

Authors:

arXiv:2507.03065v2 Announce Type: replace Abstract: Why do some macroscopic structures remain identifiable even though their microscopic constituents continually change? Vortices persist while fluid parcels turn over, neural memories persist while spikes and synapses fluctuate, and institutions persist while individuals enter and leave. We propose a scale-relative answer: an emergent property is a persistent nontrivial homology class $[z]\in H_p=\ker\partial_p/\im\partial_{p+1}$, a macro-feature that is closed but not exact across a filtration of descriptions. This identification turns emergence into a measurement problem. Persistent bars detect stable macro-features, and we introduce a contractive-similarity (CS) graph operator to supply scaffold spectral gaps that predict robustness. Hodge decomposition separates harmonic macro-scaffold from exact and co-exact micro-flow; and functorial condensation explains when one level's emergent class becomes a unit for the next. The resulting scaffold-flow framework expresses six familiar signatures of emergence (i.e., inevitability, coherence, irreducibility, complementarity, robustness, and hierarchy) within one mathematical language. It also yields falsifiable predictions across atmospheric, neural, and social systems: genuine emergent structures should persist across filtrations, remain spectrally stable, respond disproportionately to harmonic interventions, and require timescale separation for hierarchical autonomy.

17.
arXiv (CS.CL) 2026-06-16

EIBench: A Simulator-Based Benchmark and Turn-Credit RL for Emotion Management

Emotional intelligence (EI) in Large Language Models (LLMs) is often evaluated through static understanding tasks or single-response dialogue generation. However, emotion management is interactive: a good model should not only recognize a user's emotion, but also improve the user's emotional and relational state over several turns. We introduce EIBench, a simulator-based benchmark for interactive emotion management. EIBench contains 2,222 scenarios, with 2,009 for training and 213 for held-out testing. The scenarios are organized by a 2x2 taxonomy covering Support, Defense, Repair, and Charm, which together capture different forms of support, boundary maintenance, trust repair, and rapport building. In each scenario, an LLM simulator plays the user, updates an emotion-relation state after each turn, and maps the final state to an anchor-based score. This design makes EIBench both an evaluation benchmark and a training environment: the final state gives the outcome reward, while the per-turn state updates provide dense feedback for RL. We evaluate 15 open- and closed-source LLMs. Current models perform well on support and rapport-building scenes, but struggle with boundary maintenance under user pressure. To improve the EI ability of LLMs, we propose Centered Turn-Credit GRPO (CTC-GRPO), a GRPO extension that reuses the simulator's per-turn state updates as dense turn-level feedback while preserving the final outcome reward. CTC-GRPO improves Qwen3-8B from -22.4 to +22.4 on EIBench and also improves on out-of-distribution evaluations including SAGE (+12.4) and EQBench3 (+20.9%). Our results show that simulator-tracked user states can support both evaluation and training for multi-turn emotion management.

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

Uncertainty Estimation and Generalization Bounds for Modern Deep Learning

arXiv:2606.13818v1 Announce Type: new Abstract: This thesis investigates how Bayesian principles can deepen our understanding of modern deep learning systems. While neural networks achieve remarkable predictive performance, their ability to generalize and to quantify uncertainty remains only partly understood. This thesis approaches this challenge from both methodological and theoretical angles: unifying Bayesian inference, function-space modeling, and large-deviation theory under a common probabilistic perspective. On the methodological side, the thesis introduces the Deep Variational Implicit Process (DVIP), a scalable Bayesian framework that extends implicit processes to deep architectures. Complementing this, two post-hoc methods – the Variational Linearized Laplace Approximation (VaLLA) and the Fixed-Mean Gaussian Process (FMGP) – are proposed to equip pretrained deterministic networks with calibrated uncertainty estimates. The theoretical contributions focus on one of the central open questions in modern machine learning: why do large, over-parameterized neural networks generalize so well? To address this, the thesis develops a unified probabilistic framework that connects three key mechanisms – diversity, smoothness, and stochasticity – within the language of PAC-Bayesian and large-deviation theory.

19.
arXiv (CS.AI) 2026-06-15

Q-Net: Queue Length Estimation via Kalman-based Neural Networks

arXiv:2509.24725v4 Announce Type: replace-cross Abstract: Estimating queue lengths at signalized intersections is a long-standing challenge in traffic management. Partial observability of vehicle flows complicates this task despite the availability of two privacy-preserving data sources: (i) aggregated vehicle counts from loop detectors near stop lines, and (ii) aggregated floating car data (aFCD) that provide segment-wise average speed measurements. However, how to integrate these sources with differing spatial and temporal resolutions for queue length estimation is rather unclear. Addressing this question, we present Q-Net: a queue estimation framework built upon a state-space formulation. This design addresses key challenges in queue modeling, such as violations of traffic conservation assumptions. Q-Net follows the Kalman predict-update structure and maintains physical interpretability in both the state evolution and measurement models. Q-Net uses an AI-augmented Kalman filter to learn time-varying gain dynamics from data. The framework supports real-time implementation and improves spatial transferability by grouping aFCD measurements into fixed-size local groups, making the number of learnable parameters independent of section length. Evaluations on urban main roads in Rotterdam, the Netherlands, show that Q-Net outperforms baseline methods, tracks queue formation and dissipation accurately, and mitigates aFCD-induced delays. By combining data efficiency, interpretability, real-time applicability, and spatial transferability, Q-Net makes accurate queue length estimation possible without costly sensing infrastructure like cameras or radar.

20.
bioRxiv (Bioinfo) 2026-06-18

A data-driven rediscovery of the specificity-conferring code of adenylation domains in nonribosomal peptide synthetases

Nonribosomal peptide synthetases (NRPSs) are large modular enzymes that assemble structurally diverse peptides, many of pharmacological importance, including antibiotics and immunosuppressants. Within each NRPS module, the adenylation (A) domain selects the substrate to be incorporated, a choice governed by a small set of residues lining the binding pocket. For two decades, computational prediction of A-domain substrate specificity has relied on residue sets - most prominently the Stachelhaus code and the 34-residue "8 Angstrom code" - that were defined by spatial proximity to the substrate rather than by demonstrated predictive value. Here we revisit which residues govern substrate specificity from a purely data-driven perspective. We assembled a non-redundant dataset of 5,366 A-domain sequences (4,693 bacterial and 673 fungal) and used information-theoretic measures to rank alignment positions by their statistical association with substrate identity, without restricting candidate positions to any predefined structural shell. This procedure yielded two compact, kingdom-specific codes: IG15B (15 positions) for bacterial and IG13F (13 positions) for fungal A-domains. Both match or exceed the predictive accuracy of the 34-residue 8 Angstrom code while using fewer than half its positions, and both independently recover the majority of the classical Stachelhaus positions. Notably, our analysis identifies four positions (242, 280, 281, and 284) that lie outside all conventional codes yet carry non-redundant specificity information and co-localize with classical determinants on two helices flanking the binding pocket. These positions provide new candidate sites for the rational engineering of A-domain specificity.

21.
medRxiv (Medicine) 2026-06-16

Recurrence After Hepatic Hydatid Cyst Surgery: Scolicidal Agent Application Technique and the Effect of Cystopiliary Fistula

Objective: This study aimed to evaluate long-term outcomes in patients who underwent surgical treatment for hepatic hydatid cyst (HCC) disease and, in particular, to investigate the effect of scolicidal agent (SA) application method and the presence of cystobiliary fistula (CBF) on the development of recurrence. Materials and Methods: This single-center, retrospective study included 197 patients who underwent surgical treatment for HCC disease. Hypertonic saline was used as SA in all patients and was classified as intracystic or pericystic application according to the application method. The presence of CBF was evaluated according to intraoperative and postoperative findings. Patients were followed for 86 months, and the development of recurrence was identified by radiological methods. Comparisons were made between the groups with and without recurrence in terms of SA application method and the presence of CBF. Results: The median age of the patients was 38 years, and the median follow-up period was 86 months. SA application was performed into the cyst in 51.3% of the patients and around the cyst in 48.7%. The presence of CBF was detected in 49.7% of the patients. No statistically significant difference was found between the recurrent and non-recurrent groups in terms of SA application method (p = 0.344). Similarly, no significant relationship was found between the presence of CBF and the development of recurrence (p = 0.721). Conclusion: This study showed that the SA application method and the presence of CBF are not determinants of recurrence in HCC disease. It is thought that recurrence rates can be kept low with appropriate surgical technique and effective biliary tract management.

22.
arXiv (math.PR) 2026-06-16

Collapsibility in Multiparametric Models of Random Simplicial Complexes

Authors:

arXiv:2606.15276v1 Announce Type: cross Abstract: We study collapsibility in the multiparametric models of random simplicial complexes, namely the lower and upper models. In the upper model, we improve upon a result of Farber and Nowik, and assert that the homology is a.a.s concentrated in a single dimension by proving that the complex collapses to that \di. In the lower model, we prove that the complex a.a.s collapses to the \di\ with maximal non-trivial cohomology. We then compare this threshold to the ones derived previously for the special cases of the clique complex (by Kahle) and the Linial-Meshulam model.

23.
Nature (Science) 2026-06-11

‘Footballers are not superheroes’: we must tackle the mental and physical pressures of elite sport

Authors:

As the men’s football World Cup gets under way, how the game weighs on the health of athletes still isn’t talked about enough, says player-turned-medic Vincent Gouttebarge. As the men’s football World Cup gets under way, how the game weighs on the health of athletes still isn’t talked about enough, says player-turned-medic Vincent Gouttebarge.

24.
arXiv (CS.AI) 2026-06-17

DiagFlowBench: Evaluating How Language Models Handle Off-Procedure Inputs in Grounded Diagnostic Dialogue

arXiv:2606.17904v1 Announce Type: new Abstract: Language models increasingly serve as advisory systems in maintenance operations. To prevent hallucination, recent systems ground these models in procedural documentation to constrain them to approved steps. In practice, however, operator queries frequently stray from this path, requiring models to recognise out-of-scope inputs mid-conversation, a dynamic that current benchmarks rarely prioritise. We introduce DiagFlowBench, a dataset of 50 industrial diagnostic flowcharts from a consumer manufacturer converted into 1,676 multi-turn conversations that contrast compliant with out-of-scope utterances. Evaluating a panel of ten commercial and open-weight models reveals high variability in abstention rates, with models commonly selecting a real but contextually inadequate step rather than fabricating facts. The inherent plausibility and authority of this mapped but wrong advice exposes a challenging vulnerability for grounding systems.

25.
arXiv (quant-ph) 2026-06-16

Against probability: A quantum state is more than a list of probability distributions

arXiv:2601.18872v2 Announce Type: replace Abstract: The state of a quantum system can be represented by listing the outcome probabilities for a tomographically complete set of measurements. Such representations appear throughout physics, for example, in quantum field theory via correlation functions and in quantum foundations within generalized probabilistic frameworks. In this paper, we show a no-go result: To enable useful statements, the probability representation must be topologically robust$\unicode{x2014}$preserving the notion of closeness between states. Yet, a topologically robust probability representation cannot simultaneously retain other essential structure, such as the subsystem structure.