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01.
Nature (Science) 2026-06-08

Fifty years since a simple equation described the chaos of biology

An exploration of chaos theory in population dynamics showed that unpredictable systems can often be modelled using surprisingly simple mathematics. An exploration of chaos theory in population dynamics showed that unpredictable systems can often be modelled using surprisingly simple mathematics.

02.
arXiv (math.PR) 2026-06-11

Capital Asset Pricing Model with Size Factor and Normalizing by Volatility Index

arXiv:2411.19444v5 Announce Type: replace-cross Abstract: The Capital Asset Pricing Model (CAPM) relates a well-diversified stock portfolio to a benchmark portfolio. We insert size effect in CAPM, capturing the observation that small stocks have higher risk and return than large stocks, on average. For some size-based stock portfolios, dividing their returns by the Volatility Index makes them closer to independent and normal. In this article, we combine these ideas to create a new discrete-time model, which includes volatility, relative size, and CAPM. We fit this model using real-world data, prove the long-term stability, and connect this research to Stochastic Portfolio Theory. We fill important gaps in our previous article on CAPM with the size factor.

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

GraphWorld: Long-Horizon Planning with World Models for End-to-End Autonomous Driving

End-to-end autonomous driving has made significant progress by unifying perception, prediction, and planning within a single learning framework, achieving strong performance in short-horizon decision making. However, most existing E2E-AD methods remain confined to short-horizon planning and lack the ability to model long-term temporal dependencies, which severely limits their generalization and security in complex and highly interactive driving scenarios. In this work, we propose GraphWorld, an E2E-AD framework that explicitly enhances long-horizon planning through latent world modeling. We introduce an Ego-Centric Interaction Graph, which adaptively models critical neighboring agents based on spatial proximity, and propagates relational context to planning queries via cross-node cross-attention. We present a World-State-Conditioned Planning that learns ego-centric latent world representations by modeling interactions between an ego vehicle and surrounding agents. This latent world state captures key interaction dynamics and safety-relevant semantics, and serves as a conditioning signal to guide long-horizon, safety-aware trajectory planning. Extensive experiments on Bench2Drive, NAVSIMv1/2, and nuScenes demonstrate that GraphWorld significantly reduces collision rates and improves long-horizon planning performance, validating its effectiveness in complex driving environments.

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

CAVEWOMAN: How Large Language Models Behave Under Linguistic Input and Output Compression

"Talk short. Drop grammar. Save token." This caveman style is widely promoted as a way to cut inference cost, but whether it actually saves anything depends on which channel (the user's prompt or the model's response) is being compressed. We present Cavewoman, a two-channel evaluation protocol that scores every generation on task accuracy, realized per-item cost, and reference-text agreement against the model's unconstrained reference. We evaluate eight models on five datasets at five reduction levels, with both channels measured on the same items. Output compression cuts realized cost on most API models (1.4-2.4x per model, up to 3x in the best case) and on all four open-weight models under public-tier pricing. Input compression has the opposite effect, a strict lose-lose: it raises net cost rather than lowering it (~1.15x on the five-benchmark mean, up to 1.8x on the worst dataset and 2.7x under stronger compression), because models compensate with longer responses even as accuracy collapses. Under the same setting, surface text diverges from the unconstrained reference: on the non-reasoning models, roughly half of all generations are correct yet their surface text no longer entails the model's own unconstrained baseline generation. The divergence survives length-controlled re-scoring, multiple-comparisons correction, and replication under complementary semantic measures. Code and data are available at https://github.com/danielle34/cavewoman.

05.
arXiv (quant-ph) 2026-06-11

Random Grover Search

arXiv:2606.11759v1 Announce Type: new Abstract: Grover's algorithm achieves a quadratic speedup for unstructured search given a global oracle for the target set. In many applications, however, the target set is specified as the intersection of multiple constraint sets. Constructing a global oracle for the intersection can be costly, whereas the individual constraint oracles are often much simpler to implement. We study a randomized Grover search algorithm that directly uses these constraint oracles. At each iteration, one of the corresponding Grover operators is selected at random. For the two-operator case with uniform sampling, we prove that the success probability approaches one after \[ \Theta \left(\frac\pi4\sqrt{\frac{N}{r}}\right) \] iterations, where $r$ is the size of the intersection. Thus, the algorithm achieves the same asymptotic query complexity as standard Grover search but without requiring a global oracle. We then generalize the analysis to arbitrary sampling distributions and an arbitrary number of Grover operators through an auxiliary operator that approximates the expected Grover evolution, while retaining the same asymptotic complexity. We further show that highly biased sampling distributions can still achieve near-unit success probability, enabling cheaper Grover operators to be used more frequently. Finally, we prove asymptotic optimality and support the theoretical results with numerical simulations.

06.
medRxiv (Medicine) 2026-06-12

Microbial etiology, antibiotic susceptibility profiles, and multidrug resistance of urinary tract infections at a secondary healthcare facility in Ghana

Background: Rising antibiotic resistance challenges empirical therapies for urinary tract infections (UTIs). This study evaluated the microbial etiology, susceptibility profiles, and multidrug resistance (MDR) patterns of uropathogens among outpatients at the Berekum Holy Family Hospital, Ghana. Methods: This cross-sectional study (February to August 2021) screened 263 symptomatic outpatients. Mid-stream urine samples underwent quantitative culture, biochemical identification, and antimicrobial susceptibility testing via the Kirby-Bauer disc diffusion method following the 2021 CLSI guidelines. Results: Significant bacteriuria prevalence was 22.8% (60/263). UTIs predominated in females (78.3%, 47/60; p = 0.1501) and individuals [≥]45 years (33.3%, 20/60). Gram-negative rods accounted for 90.0% of isolates, primarily Escherichia coli (26.7%), Citrobacter spp. (25.0%), and Enterobacter spp. (21.7%); Staphylococcus aureus (10.0%) was the only Gram-positive pathogen. Extreme phenotypic resistance was observed against piperacillin/tazobactam (98.3%), cefotaxime (93.3%), tetracycline (88.3%), and cefoperazone (85.0%). Conversely, highest therapeutic susceptibilities were retained by amikacin (78.3%), levofloxacin (61.7%), and gentamicin (58.3%). Conclusion: The high prevalence of MDR uropathogens against advanced beta-lactamase inhibitor combinations and cephalosporins necessitates an immediate re-evaluation of regional empirical protocols. Amikacin, levofloxacin, and gentamicin remain viable options prior to culture confirmation. These findings establish a crucial phenotypic baseline to guide localized prescribing policies and regional antimicrobial resistance tracking strategies.

07.
arXiv (CS.AI) 2026-06-15

A fully GPU-based workflow for building physics emulators of hypersonic flows

arXiv:2606.13742v1 Announce Type: cross Abstract: The ability to resolve complex physical phenomena with high fidelity and at low computational cost is central to addressing key challenges in modern engineering. A prime example lies in hypersonic flows, where the precise prediction of the full flowfield topology, in particular with respect to shock wave location and intensity, is critical. Yet supersonic and hypersonic flows continue to be a stumbling block for traditional reduced-order models and neural emulators that struggle to capture steep gradients in flow states with physical consistency in applications of industrial relevance. To that end, we introduce a fully GPU based workflow that integrates accelerated data generation with the training of neural emulators augmented by uncertainty quantification and physics-aware refinement. Our workflow is enabled by a differentiable high-fidelity solver (JAX-Fluids) which we employ for rapid dataset creation and residual-based improvement of the neural emulator to enhance physical consistency. Building on this framework, we first present a suite of model architectures and analyze their scaling behavior to expose their strengths and shortcomings. We then show that residual-based refinement enables training on cases where only mesh and input parameters are available, substantially reducing residuals and improving physical consistency. Together, differentiable simulation and residual-based refinement yield physics emulators that remain reliable beyond their training distribution, a key requirement for deploying surrogates in real-world engineering design loops.

08.
arXiv (CS.CV) 2026-06-15

Stream3D: Sequential Multi-View 3D Generation via Evidential Memory

View-conditioned 3D generators such as SAM 3D, TRELLIS, and Hunyuan3D produce high-quality object reconstructions from a single view, but real-world visual observation often arrives as long monocular streams. Naively applying these generators to each streaming frame independently leads to severe temporal inconsistency in the generated results. To address this problem, we propose Stream3D, the first training-free streaming mechanism that turns a frozen view-conditioned 3D generator into a streaming generator with constant cross-chunk memory. Stream3D achieves this by maintaining a compact evidential memory, which selectively caches the most informative historical frames based on a proposed evidence score mechanism. As the stream progresses, the memory dynamically updates to retain a fixed number of informative frames, preventing the memory footprint from growing linearly with sequence length. This also prevents degradation over long sequences and keeps the underlying generator completely unchanged without retraining, architectural modifications, or auxiliary losses. Evaluated on both realistic and synthetic streaming benchmarks, Stream3D outperforms latent-transport baselines, including KV-cache reuse and flow-based feature editing, across both photometric and geometric metrics. More details can be found at: https://stream-3d.github.io/stream3d.github.io/.

09.
arXiv (CS.LG) 2026-06-19

Pseudo-Formalization for Automatic Proof Verification

arXiv:2605.20531v2 Announce Type: replace-cross Abstract: Reliable verification of proofs remains a bottleneck for training and evaluating AI systems on hard mathematical reasoning. Fully formal proofs, in languages like Lean, are easy to verify because they are unambiguous and modular. Most proofs, particularly those written by AI systems, have neither property, and translating them into formal languages remains challenging in many frontier math settings. We propose Pseudo-Formalization (PF), a proof format that captures the modularity and precision of formal proofs while retaining the flexibility of natural language. A Pseudo-Formal proof is decomposed into self-contained modules, each stating its premises, conclusion, and proof in natural language. To verify the correctness of a regular natural language proof, an LLM translates it to Pseudo-Formal and then verifies each module independently, an algorithm we call Block Verification (BV). We evaluate PF+BV on two benchmarks spanning olympiad and research-level mathematics, where it pareto-dominates LLM-as-judge baselines on error-finding precision and recall. To support future work, we release our research-level proof verification benchmark ArxivMathGradingBench.

10.
arXiv (quant-ph) 2026-06-11

Single Photon Cross-Phase Shifts Can Be Enhanced by Localization in both Frequency and Time

arXiv:2606.11516v1 Announce Type: new Abstract: Single-photon optical nonlinearities face a fundamental trade-off: maximum nonlinearity requires both spectral resonance (narrow bandwidth) and high peak intensity (short duration), constraints that are incompatible due to the time-energy uncertainty relation. We demonstrate experimentally that this limitation does not need to exist in cases involving post-selection. We measure a cross-phase shift (XPS) produced by a resonant photon from a narrow-band source that is first transmitted through a cold atomic cloud and then localized in time through detection. The peak size of this XPS is greatly enhanced compared to that of Gaussian single-photon-level pulses without post-selection, benefiting from the narrow bandwidth of the resonant prepared state and the high intensity of the post-selected state simultaneously. We measure enhancements in the peak XPS of 6$\pm$1 at an optical depth (OD) of 2.4$\pm$0.1, and our results are in qualitative agreement across a range of optical depths with the recently developed weak value theory of atomic excitation [Thompson et al., APL Quantum 2, 036108 (2025)] for such post-selected photons. This work uncovers new consequences of having simultaneous knowledge of frequency and time, raising new foundational questions about how a particle behaves, and interacts with other systems, when its preparation and post-selection are non-commuting.

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

SAGE: Scalable AI Governance & Evaluation

arXiv:2602.07840v4 Announce Type: replace-cross Abstract: Evaluating relevance in large-scale search systems is fundamentally constrained by the governance gap between nuanced, resource-constrained human oversight and the high-throughput requirements of production systems. While traditional approaches rely on engagement proxies or sparse manual review, these methods often fail to capture the full scope of high-impact relevance failures. We present SAGE (Scalable AI Governance \& Evaluation), a framework that operationalizes high-quality human product judgment as a scalable evaluation signal. At the core of SAGE is a bidirectional calibration loop where natural-language Policy, curated Precedent, and an LLM Surrogate Judge co-evolve. SAGE systematically resolves semantic ambiguities and misalignments, transforming subjective relevance judgment into an executable, multi-dimensional rubric with near human-level agreement. To bridge the gap between frontier model reasoning and industrial-scale inference, we apply teacher-student distillation to transfer high-fidelity judgments into compact student surrogates at 92$\times$ lower cost. Deployed within LinkedIn Search ecosystems, SAGE guided model iteration through simulation-driven development, distilling policy-aligned models for online serving and enabling rapid offline evaluation. In production, it powered policy oversight that measured ramped model variants and detected regressions invisible to engagement metrics. Collectively, these drove a 0.25\% lift in LinkedIn daily active users.

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

ClinHallu: A Benchmark for Diagnosing Stage-Wise Hallucinations in Medical MLLM Reasoning

Building trustworthy medical multimodal large language models (MLLMs) is critical for reliable clinical decision support. Existing medical hallucination benchmarks mainly focus on data collection, but often ignore where hallucinations originate within the reasoning process. We find that hallucination sources vary across samples: errors may arise from visual misrecognition, incorrect medical knowledge recall, or flawed reasoning integration. To enable source-level hallucination diagnosis, we introduce ClinHallu, a benchmark for stage-wise hallucination diagnosis in medical MLLM reasoning. ClinHallu contains 7,031 validated instances, where each instance is augmented with a structured reasoning trace decomposed into Visual Recognition, Knowledge Recall, and Reasoning Integration. We also use stage-replacement interventions to measure how correcting specific stages affects the final answer. Beyond evaluation, we show that trace-supervised fine-tuning reduces stage-wise hallucinations. ClinHallu provides a fine-grained hallucination testbed for diagnosing and mitigating reasoning failures in medical MLLMs. The benchmark is publicly available at https://github.com/alibaba-damo-academy/ClinHallu.

13.
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.

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

EvoBrowseComp: Benchmarking Search Agents on Evolving Knowledge

Search Agents – large language models augmented with search tools – have intensified the need for future-proof evaluation benchmarks. Existing benchmarks such as BrowseComp rely on static knowledge, making them vulnerable to test-set contamination and parametric memorization. Consequently, models can achieve high scores through fact recall rather than genuine retrieval, obscuring true browsing competence via reasoning shortcuts. In this paper, we introduce EvoBrowseComp, an evolving benchmark of 400 English and 400 Chinese contamination-free complex questions synthesized via live-web traversal. To collect these questions, we design a three-agent collaborative framework: (1) a QA synthesis agent that retrieves fresh knowledge from the live web to synthesize QA pairs; (2) an information filtering agent that filters retrieved knowledge in terms of credibility and popularity to block parametric shortcuts; and (3) a high-level guidance agent that formalizes questions into reasoning graphs to reduce logical redundancy and shortcuts in synthesized QA pairs. Because the framework supports fully automated synthesis, EvoBrowseComp can be regularly updated to prevent data contamination and maintain temporal freshness. Extensive experiments confirm its great difficulty, requiring broad horizontal search. It establishes a scalable paradigm for auto-updatable, high-difficulty benchmarking that keeps pace with both evolving world knowledge and advancing agent capabilities.

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

Assessing Distribution Shift in Human Activity Recognition for Domain Generalization

arXiv:2606.24781v1 Announce Type: new Abstract: While the field of Human Activity Recognition (HAR) continues to draw interest from researchers and advance in important ways, some key challenges remain. One of the most difficult aspects of building HAR models that show good performance in real-world settings is dealing with data diversity from device and sensor heterogeneity, and contextual changes that are intrinsic to real-world applications. While data diversity in HAR has been well-acknowledged in the literature, there remains a gap in understanding the effect of various types of distribution shifts on HAR models and the domain generalization problem that arises. Towards that end, this paper systematically evaluates 4 different types of distribution shifts, including variations in device type, sensor placement, sampling rate, and user behavior. Quantifying their effects, we illustrate that diversity shifts predominantly define all types of shifts, indicating the existence of unique features that are not shared across different domains. We then introduce a uniform HAR-based distribution shift benchmarks and conduct a comprehensive evaluation of up to 28 domain generalization methods. Our analysis exposes the limitations of current domain generalization algorithms in achieving model generalizability, marginally outperforming the empirical risk minimization baseline. This work represents the first systematic exploration of domain generalization and adaptation concerning specific distribution shifts in sensor-based HAR, offering an open-source benchmark platform and datasets to spur further research.

16.
arXiv (CS.CL) 2026-06-25

Paid Voices vs. Public Feeds: Interpretable Cross-Platform Theme-Based Analysis of Climate Discourse

Climate discourse online shapes public understanding of climate change and informs political and policy debate, yet it unfolds across structurally different environments: paid advertising platforms host targeted, institutionally produced messaging, while public social media reflects largely organic, user-driven discussion. We present a comparative analysis of climate discourse across paid advertisements on Meta (previously Facebook) and public posts on Bluesky from July 2024 to September 2025. To support it, we develop an interpretable thematic discovery pipeline that clusters texts by semantic similarity and uses large language models (LLMs) to label clusters with concise, human-interpretable themes, requiring no predefined topic inventory or seed set. Using these themes, we find the two environments diverge systematically: paid advertising centers on strategic promotion of specific solutions in a formal, forward-looking register, whereas organic discourse centers on systemic critique in a crisis-oriented, scientifically grounded one. We also evaluate the utility of the discovered themes through downstream stance prediction and theme-guided retrieval tasks. While our analysis focuses on climate communication, the framework generalizes to comparative thematic analysis across heterogeneous communication environments.

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

Stochastic Expectation Maximization for Robust State-Space Radio Interferometric Imaging

arXiv:2606.23944v1 Announce Type: cross Abstract: State–space models provide a flexible framework for analyzing dynamical systems, yet they often rely on Gaussian assumptions that fail to capture heavy-tailed or outlier-prone measurement noise. We propose a robust estimation scheme for linear state–space models subject to compound-Gaussian noise, as encountered for instance in radio interferometry affected by radio-frequency interference (RFI). The method relies on a Stochastic Approximation Expectation–Maximization (SAEM) algorithm in which the standard E-step is replaced by Monte Carlo sampling of the latent states and noise texture through closed-form Gibbs updates, enabling tractable inference despite the heavy-tailed likelihood. Numerical experiments show that the proposed method significantly improves reconstruction fidelity and robustness to RFI, outperforming a Gaussian EM algorithm and even an oracle RTS smoother. These results highlight the benefits of heavy-tailed state–space modeling and SAEM-based inference in interference-dominated imaging scenarios.

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

ROSE: Benchmarking the Perception-to-Action Gap in Multimodal Models

arXiv:2606.19965v1 Announce Type: cross Abstract: Multimodal large language models (MLLMs) are increasingly expected to act on visual information, yet the same scene may require different actions under different task contexts. How reliably can a model turn the same visual evidence into the action required by the current context? To answer this question, we introduce \textsc{ROSE} (Reference-conditioned Oddity and Symbolic Execution), a controlled benchmark that holds the visual scene fixed while varying region constraints and required symbolic outputs. Through coupled counting and coordinate-action tasks, \textsc{ROSE} tests whether models can infer an implicit majority reference and act on the resulting fine-grained visual evidence under changing contexts. Across nine recent MLLMs, performance drops by as much as 44.5 percentage points from counting-oriented tasks to region-conditioned action, despite 98.8\% human performance. The gap persists on paired scenes and regions for which the same model returns the correct count, while global-click and matched local controls show that coordinate grounding explains only part of the loss, revealing a distinct, model-dependent bottleneck in turning shared visual evidence into context-specific actions.

19.
arXiv (CS.AI) 2026-06-11

Resource-Aware LLM Reasoning for Mobile Edge General Intelligence

arXiv:2509.23248v3 Announce Type: replace Abstract: The rapid advancement of large language models (LLMs) has enabled an emergence of agentic artificial intelligence (AI) with powerful reasoning and autonomous decision-making capabilities. This integration with edge computing has led to the development of Mobile Edge General Intelligence (MEGI), which brings real-time, privacy-preserving reasoning to the network edge. However, deploying LLM-based agentic AI reasoning in MEGI environments poses significant challenges due to the high computational demands of reasoning and the limited resources of edge devices. To address these challenges, we propose a joint optimization framework for efficient LLM reasoning deployment in MEGI. First, we systematically review enhancement methods to identify mechanisms suitable for edge adaptation. Subsequently, we present a distributed framework that synergizes reasoning enhancement via adaptive CoT prompting with scalable deployment through a distributed MoE architecture. An important innovation of this approach involves modeling reasoning depth as a dynamic network resource variable, which is optimized jointly with expert activation and transmission power. This mechanism allows the system to dynamically regulate expert networks and reasoning complexity according to task requirements and device capabilities. Experimental evaluations in mobile edge environments demonstrate that the proposed framework effectively balances reasoning quality and resource efficiency. The results show that with less than one second of additional inference time, both accuracy and latency satisfaction rate can reach 90\%, validating the practical viability of deploying sophisticated LLM reasoning in resource-constrained MEGI systems.

20.
arXiv (CS.LG) 2026-06-17

Searching Neural Architectures for Sensor Nodes on IoT Gateways

arXiv:2505.23939v2 Announce Type: replace Abstract: This paper presents an automatic method for the design of Neural Networks (NNs) at the edge, enabling Machine Learning (ML) access even in privacy-sensitive Internet of Things (IoT) applications. The proposed method runs on IoT gateways and designs NNs for connected sensor nodes without sharing the collected data outside the local network, keeping the data in the site of collection. This approach has the potential to enable ML for Healthcare Internet of Things (HIoT) and Industrial Internet of Things (IIoT), designing hardware-friendly and custom NNs at the edge for personalized healthcare and advanced industrial services such as quality control, predictive maintenance, or fault diagnosis. By preventing data from being disclosed to cloud services, this method safeguards sensitive information, including industrial secrets and personal data. The outcomes of a thorough experimental session confirm that – on the Visual Wake Words dataset – the proposed approach can achieve state-of-the-art results by exploiting a search procedure that runs in less than 10 hours on the Raspberry Pi Zero 2.

21.
Nature Medicine 2026-06-10

Dual-target gene therapy in Parkinson’s disease: a multicenter phase 1 trial

作者:

Restoring striatal dopamine synthesis is a promising gene therapy strategy for Parkinson’s disease. Previous adeno-associated virus-mediated aromatic L-amino acid decarboxylase (AADC) monotherapies remain dependent on exogenous levodopa, whereas multigene delivery is constrained by strict adeno-associated virus packaging limits. A ‘dual approach’ targeting the two rate-limiting enzymes, tyrosine hydroxylase (TH) and AADC, offers the potential for autonomous dopamine synthesis. We report the 12-month primary safety and tolerability outcomes of a multicenter, open-label, dose-escalation, phase 1 trial evaluating BBM-P002, a new adeno-associated virus vector—AAVT42—codelivering constitutively active TH and AADC. Ten participants with moderate-to-advanced Parkinson’s disease were enrolled and received bilateral intraputaminal infusions across doses of 4.0 × 1011 vg (Cohort 1; n = 1), 6.0 × 1011 vg (Cohort 2; n = 2), 1.0 × 1012 vg (Cohort 3; n = 2) and 1.2 × 1012 vg (Cohort 4; n = 5). The trial achieved its primary outcome, as BBM-P002 demonstrated a favorable safety and tolerability profile within 12 months post-treatment. No dose-limiting toxicities or drug-related serious adverse events occurred. A total of 23 adverse events were reported, all judged unrelated to BBM-P002 and primarily mild and transient. Systemic toxicity and clinically meaningful immunogenicity were absent. In conclusion, intraputaminal delivery of BBM-P002 was safe and well tolerated in this phase 1 trial, supporting continued clinical development. ClinicalTrials.gov registration: NCT05822739 . Phase 1 results reveal that BBM-P002, a dual-target gene therapy co-delivering TH and DDC, is safe and well tolerated in Parkinson’s disease, with 12-month motor improvements signaling therapeutic potential.

22.
arXiv (CS.AI) 2026-06-12

Mechanical Conscience: A Mathematical Framework for Dependability of Machine Intelligenc

arXiv:2605.03847v2 Announce Type: replace Abstract: Distributed collaborative intelligence (DCI), encompassing edge-to-edge architectures, federated learning, transfer learning, and swarm systems, creates environments in which emergent risk is structurally unavoidable: locally correct decisions by individual agents compose into globally unacceptable behavioral trajectories under uncertainty. Existing approaches such as constrained optimization, safe reinforcement learning, and runtime assurance evaluate acceptability at the level of individual actions rather than across behavioral trajectories, and none addresses the multi-participant, uncertainty-laden nature of DCI deployments. This paper introduces mechanical conscience (MC), a novel concept and simplified mathematical framework that operationalizes trajectory-level normative regulation for both single-agent and distributed intelligent systems. Mechanical conscience is defined as a supervisory filter that minimally corrects a baseline policy's actions to reduce cumulative deviation from a normatively admissible region, while accounting for epistemic uncertainty. We introduce associated constructs, conscience score, mechanical guilt, and resonant dependability, that provide an interpretable vocabulary and computable governance signals for this emerging field. Core theoretical properties are established: admissibility equivalence, existence of optimal regulation, and monotonic deviation reduction. Illustrative results demonstrate that MC-regulated agents maintain trajectory-level normative acceptability where conventional controllers drift outside admissible bounds, and that the framework naturally extends to suppress interaction-induced emergent risk in multi-agent DCI settings.

23.
medRxiv (Medicine) 2026-06-22

Discovering Novel intracranial EEG Biomarkers of Seizure Generating Tissue through Time-Frequency Analysis

Objective: EEG biomarkers for seizure-generating tissue have historically been identified visually, which lacks objectivity and limits utility of automated approaches. For example, high frequency oscillations and interictal epileptiform discharges were promising markers to improve surgical outcomes for refractory epilepsy, but low specificity has hindered clinical implementation, and automated algorithms have not improved this. Methods: We developed Intracranial EEG Pattern Identification and Categorization, an automated, data-driven time-frequency framework for EEG biomarker discovery. It detects transient high-power intracranial EEG waveforms (1-500 Hz) and characterizes them using eight features. In seizure-free patients, waveforms occurring predominantly in resected intracranial EEG channels are candidate biomarkers. Results: In retrospective data from 14 seizure-free post-surgical patients from University of California, Los Angeles, we identified 9 waveform categories strongly associated with resected intracranial EEG channels. These included beta, gamma, and ripple band bursts, sometimes co-occurring with interictal epileptiform discharges; however, many were visually imperceptible in the broadband EEG. Using a support vector machine, we generated a unified classification metric based on these waveforms and tested it on 87 seizure-free subjects from Detroit Medical Center. This metric achieved higher area under the precision-recall curve than six state-of-the-art benchmark algorithms (p

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

S-GBT: Smooth Growth Bound Tensor for Certified Robustness Against Word Substitution Attacks in NLP

Despite recent progress in Natural Language Processing (NLP), models remain vulnerable to word substitution attacks. Most existing defenses focus on first order sensitivity and measure how much the output changes when the input is slightly perturbed. However, they ignore how this sensitivity evolves, which is described by curvature. When gradients vary sharply, models can still fail. This paper introduces the Smooth Growth Bound Tensor (S-GBT), a second order method that bounds the Hessian element-wise, for which we provide formal theoretical proofs on the resulting robustness bounds. A regularization term is added during training to minimize these bounds. This yields tighter certified robustness against word substitution attacks. The change in the output under word substitution is bounded by both a linear term and a quadratic term. S-GBT is derived for two architectures: Long Short-Term Memory (LSTM) and Convolutional Neural Networks (CNN). The method is integrated directly into the training objective. Its effectiveness is evaluated on multiple benchmark datasets. The results show that combining first and second order regularization improves certified robust accuracy by up to 23.4% compared to prior methods, while clean accuracy remains competitive. These findings indicate that controlling both the gradient and its variation is a promising direction for building more robust models.

25.
arXiv (CS.CL) 2026-06-17

Fine-tuning LLMs for Passive Depression Severity Estimation from AI Mental Health Dialogue

Depression is the leading cause of disability worldwide, and early detection of symptom change is essential for timely intervention. Validated instruments such as the Patient Health Questionnaire-9 (PHQ-9) support symptom monitoring at scale, but real-world completion rates are low, introducing response bias and systematic missingness. Passive approaches that infer severity from routinely generated data could close this gap. We address this by predicting PHQ-9 total scores directly from transcripts of conversations between users and an AI mental health application, requiring only conversation text and no additional clinical data. We fine-tune a Qwen3.5-27B backbone with a regression head, augment 3,111 ground-truth labels with pseudolabels generated by a reasoning model (Claude Opus) and iteratively trained intermediate models, for a combined dataset of 6,283 users. On a held-out test set of 842 users, our best model achieves MAE = 2.6, RMSE = 4.0, Pearson r = 0.80, and AUC = 0.91 at the PHQ-9 >= 10 clinical threshold. We also find AUC > 0.87 at every severity threshold from PHQ-9 >= 3 to PHQ-9 >= 24, demonstrating that the model captures depression severity across the full clinical spectrum. This work opens the door to passive, continuous symptom monitoring in AI mental health platforms, without requiring users to complete self-report measures.