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

From Shield to Target: Denial-of-Service Attacks on LLM-Based Agent Guardrails

arXiv:2606.14517v1 Announce Type: cross Abstract: LLM-based guardrails have emerged as a highly effective defense against prompt injection and jailbreak attacks in autonomous agents. However, we reveal that the very reasoning and task-following capabilities enabling this protection introduce a novel vulnerability: attackers can inject crafted data to trap the guardrail in extended reasoning loops, effectuating a systematic denial-of-service (DoS) attack. To systematically expose this threat, we design a beam-search optimization framework that crafts natural-language payloads to maximize guardrail reasoning length, utilizing an LLM proposer guided by a strategy bank. Based on the observation of guardrail's schema-following nature, we also provide another attack framework driven by mechanism-aware structural mutations with less computational load. The attack efficacy is systematically evaluated in two parts. First, in standalone evaluations, the attack generalizes across diverse guardrail architectures, safety templates, and agent benchmarks. Payloads optimized on a single open-source surrogate successfully transfer to eight leading model backbones (e.g., Claude, GPT, Gemini, DeepSeek, and Qwen), achieving a 13–63$\times$ token amplification. Second, in end-to-end real-world agent deployments (web, desktop, code, and multi-agent systems), the attack reveals up to a 148$\times$ latency amplification. We show that a single poisoned document can saturate shared guardrail infrastructures, effectively starving co-located agents and paralyzing the entire system. By uncovering this availability flaw, our work underscores the urgent need to develop cost-bounded, reasoning-robust guardrails.

02.
arXiv (CS.AI) 2026-06-18

NAVI-Orbital: First In-Orbit Demonstration of a Zero-Shot Vision-Language Model for Autonomous Earth Observation

arXiv:2606.18271v1 Announce Type: new Abstract: As Earth Observation data generation outpaces downlink bandwidth and human-in-the-loop processing, a widening gap has emerged between onboard collection and actionable ground intelligence. This paper presents NAVI-Orbital, a software system deployed on a Low Earth Orbit (LEO) spacecraft. On April 16, 2026, NAVI-Orbital achieved what is, to the authors' knowledge, the first in-orbit demonstration of a vision-language model performing autonomous multi-modal inference entirely onboard. NAVI-Orbital uses a local vision-language model (Gemma 3) to classify each captured scene, produce a text description of its content and the relationships between its features, and respond to operator follow-up via natural-language dialogue. The system is re-tasked through plain-English prompts in place of conventional command sequences, and is orchestrated by a graph-based state machine (LangGraph) coordinating dedicated agents for detection and dialogue. Results across ground benchmarking (88.16% accuracy on the 7,960-image curated AID benchmark), Flatsat validation, and live in-orbit captures of newly acquired, previously unseen Earth imagery (including uncorrected YAM-9 imagery, processed onboard with hardware-accelerated GPU inference and no fine-tuning for the flight instrument) demonstrate the feasibility of running foundation models on satellite-class edge computers to invert the conventional acquire-then-downlink-everything bandwidth profile through semantic compression of Earth observations in-orbit.

03.
arXiv (CS.AI) 2026-06-17

Adaptive Domain Models: Bayesian Evolution, Warm Rotation, and Principled Training for Geometric and Neuromorphic AI

arXiv:2603.18104v5 Announce Type: replace Abstract: Prevailing AI training assumes reverse-mode automatic differentiation over IEEE-754 arithmetic. The memory overhead of training relative to inference, optimizer complexity, and structural degradation of geometric properties through training are consequences of this arithmetic substrate. This paper develops an alternative training architecture grounded in three prior results: the Dimensional Type System and Deterministic Memory Management framework (Haynes 2026), which establishes stack-eligible gradient allocation and exact quire accumulation as design-time verifiable properties; the Program Hypergraph (Haynes 2026), which establishes grade preservation through geometric algebra computations as a type-level invariant; and the b-posit bounded-regime design (Jonnalagadda et al. 2025), which makes posit arithmetic tractable across hardware targets conventionally considered inference-only. Their composition enables depth-independent training memory bounded to approximately twice the inference footprint, grade-preserving weight updates, and exact gradient accumulation, applicable uniformly to loss-function-optimized and spike-timing-dependent neuromorphic models. We introduce *Bayesian distillation*, a mechanism by which the latent prior structure of a general-purpose model is extracted through the ADM training regime, resolving the data-scarcity bootstrapping problem for domain-specific training. For deployment, we introduce *warm rotation*, an operational pattern in which an updated model transitions into an active inference pathway without service interruption, with correctness formalized through PHG certificates and signed version records. The result is a class of domain-specific AI systems that are smaller and more precise than general-purpose models, continuously adaptive, verifiably correct with respect to the physical structure of their domains, and initializable from existing models.

04.
arXiv (CS.LG) 2026-06-16

Scalar-Stepsize Nonuniform Monte Carlo Optimistic Policy Iteration: A Certified Counterexample

Authors:

arXiv:2606.15978v1 Announce Type: new Abstract: Tsitsiklis proved convergence of Monte Carlo optimistic policy iteration under a uniform update structure and identified nonuniform update frequencies as a delicate obstruction. We give a certified negative answer for the natural scalar-stepsize, unnormalized asynchronous state-value recursion with fixed nonuniform state-selection probabilities. In a three-state, two-action discounted MDP, the nonuniform update frequencies induce a diagonally scaled greedy-policy mean field with a certified nonconstant attracting hybrid periodic orbit. With a bounded unbiased geometric-horizon estimator and Robbins–Monro stepsizes, the original stochastic recursion remains trapped near the cycle with positive probability and therefore fails to converge. The example pinpoints a geometric obstruction: uniform sampling gives radial residual contraction, whereas scalar nonuniform sampling anisotropically distorts the residual dynamics and can generate switched attracting cycles.

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

Semantic Router: On the Feasibility of Hijacking MLLMs via a Single Adversarial Perturbation

Multimodal Large Language Models (MLLMs) are increasingly deployed in stateless systems, such as autonomous driving and robotics. This paper investigates a novel threat: Semantic-Aware Hijacking. We explore the feasibility of hijacking multiple stateless decisions simultaneously using a single universal perturbation. We introduce the Semantic-Aware Universal Perturbation (SAUP), which acts as a semantic router, "actively" perceiving input semantics and routing them to distinct, attacker-defined targets. To achieve this, we conduct theoretical and empirical analysis on the geometric properties in the latent space. Guided by these insights, we propose the Semantic-Oriented (SORT) optimization strategy and annotate a new dataset with fine-grained semantics to evaluate performance. Extensive experiments on three representative MLLMs demonstrate the fundamental feasibility of this attack, achieving a 66% attack success rate over five targets using a single frame against Qwen.

06.
medRxiv (Medicine) 2026-06-15

Non-Parametric Ancestry Adjustment for Polygenic Scores

Modern polygenic risk scores (PRS) exhibit shifts correlated with ancestry, leading to erroneous predictions for non-European individuals when models are trained on predominantly European cohorts. Such shifts arise from, among other factors, (1) algorithmic limitations in the ability of PRS model training to detect causal variants, rather than nearby variants with ancestry-dependent correlations to the causal one, (2) under-representation of alleles with higher prevalence in non-European populations in the association study training, and (3) gene-by-environment interactions where the environment is correlated with genetic ancestry. Current ancestry-adjustment methodologies often discretize individuals into population categories and apply a simple affine mapping to reduce these genetic ancestry biases. However, such approaches provide suboptimal adjustments, particularly for admixed individuals. In this work, we introduce a detailed theoretical characterization of ancestry-dependent biases and propose novel methods based on non-parametric neighborhood techniques that provide more accurate empirical results and admit statistical consistency guarantees. Extensive experiments using the UK Biobank demonstrate the effectiveness of the proposed methods.

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

ProGRank: Probe-Gradient Reranking to Defend Dense-Retriever RAG from Corpus Poisoning

arXiv:2603.22934v3 Announce Type: replace Abstract: Retrieval-Augmented Generation (RAG) improves large language model applications by grounding generation in retrieved evidence, but also introduces corpus poisoning as a new attack surface. In this setting, an adversary injects or edits passages so that they enter the Top-$K$ results for target queries and influence downstream generation. Existing defences often rely on content filtering, auxiliary models, or generator-side reasoning, which complicates deployment. We propose ProGRank, a post hoc, training-free retriever-side defence for dense-retriever RAG. ProGRank stress-tests each query–passage pair under mild randomized perturbations, extracts probe gradients from a small fixed parameter subset, and derives two instability signals: representational consistency and dispersion risk. It then combines these signals with a score gate for reranking. ProGRank preserves the original passage content, requires no retraining, and supports a surrogate-based variant when the deployed retriever is unavailable. Experiments across datasets, retrievers, attacks, and retrieval-stage and end-to-end settings show that ProGRank improves robustness and maintains a favorable robustness–utility trade-off, including under adaptive evasive attacks.

08.
medRxiv (Medicine) 2026-06-22

Exploring the association of Obesity on Cold and Warm Autoimmune Hemolytic Anemia in San Joaquin Valley: A Retrospective Cross-Sectional Study

The relationship between obesity and specific autoimmune diseases haas been well-established, specifically due to obesity's role in promoting pro-inflammatory states. Although not much literature has been documented regarding obesity association with AIHA. As such, this study aims to assess any correlations in patients with elevated body mass index (BMI) and autoimmune hemolytic anemia (AIHA). Here we present a retrospective cross-sectional study conducted over a four-year period, across four medical centers during which a new electronic medical record was implemented. The study included 25 patients who had a previously documented history of AIHA from another facility, DAT positive with indicators of hemolysis, or DAT positive with monomer specific antisera. The patients BMI was recorded at the time of presentation to the hospital. However, for patients with a prior history of AIHA or those transferred from another facility, the BMI that was closest to the time period of when the patient was diagnosed with AIHA was used as an adjunct. Our results show that there is an association of patients with elevated BMI (>25) and AIHA; however, various other confounding variables should be taken into consideration, and further research should be done to establish a causal relationship.

09.
arXiv (CS.CL) 2026-06-17

Smarter edits? Post-editing with error highlights and translation suggestions

As MT quality increases, interest in enhanced post-editing features such as QE-derived error highlights is growing, yet evidence for their usefulness remains limited. In this work, we explore the usefulness of LLM-derived error highlights and correction suggestions based on automatic post-editing (APE). We conduct a study where professional translators (En-Nl) post-edit translations using APE error highlights and correction suggestions and compare productivity, quality and user experience to regular PE and PE with QE-derived highlights. While no condition yielded productivity or quality gains compared to regular PE, APE highlights were better received than QE-derived highlights, and correction suggestions improved overall user experience.

11.
Nature (Science) 2026-06-17

Analysis of 173,303 exomes and genomes in the Pakistan Genome Resource

Naturally occurring loss-of-function variants in human genes enable drug target discovery because they mimic pharmacological inhibition of proteins. However, the study of these genetic variants is constrained by their rarity. Sequencing of diverse populations, particularly those enriched in familial relatedness, has been postulated to promote discovery of rare genetic variants1–3. Here we present the Pakistan Genome Resource, a South Asian biobank with high familial relatedness comprising 173,303 participants, who collectively carry naturally occurring homozygous loss-of-function variants in 6,476 genes. We describe the genetic architecture of this population, associations between genes and biomarkers, the distribution of loss-of-function variants across molecular pathways, and recall-by-genotype studies of therapeutically relevant genes. The Pakistan Genome Resource expands the catalogue of human genetic variants, provides a comprehensive genetic reference resource for the Pakistani population, and demonstrates the value of studying diverse cohorts to advance human health. The Pakistan Genome Resource compiles biobank data from 173,303 individuals with high familial relatedness, broadening the catalogue of human genetic variation and establishing a population-specific genomic reference for Pakistan.

12.
arXiv (CS.AI) 2026-06-18

IOAH3: Importance-Driven Adaptive Spatial Partitioning

arXiv:2606.18280v1 Announce Type: cross Abstract: We present IOAH3 (Importance-Oriented Adaptive H3 partitioning), a computational method for constructing data-driven spatial partitions of geo-referenced observation domains. Standard approaches to spatial aggregation adopt fixed areal units, such as administrative boundaries or uniform hexagonal grids at a single resolution, without regard to the informational content of the underlying observations in each region. This leads to the well-known modifiable areal unit problem: statistical and inferential results depend on the arbitrary choice of partition, and spatially concentrated phenomena are averaged out in coarse cells that obscure fine-scale structure. IOAH3 addresses this by constructing an adaptive partition in three stages: multi-source feature extraction and importance scoring via principal component analysis over road density, POI density, building density, and terrain roughness signals, with population and flood-hazard data entering as auxiliary inputs to cell filtering and spatial smoothness; spatial cell selection via Markov Random Field graph-cut optimisation, which jointly maximises per-cell importance while enforcing spatial contiguity; and data-driven hierarchical refinement of high-importance regions to finer H3 resolution levels, with neighbour-propagated support to avoid isolated fine-resolution islands. The resulting partitions serve as input to spatial inference pipelines and provide a principled resolution of the partition-sensitivity problem prior to any modelling step.

13.
arXiv (CS.AI) 2026-06-24

Fast and Slow Variational Continual Learning

arXiv:2606.24007v1 Announce Type: cross Abstract: Continual learning remains a major challenge for modern deep networks, partly because commonly used optimizers lack inherent mechanisms for continual adaptation. One such natural mechanism is fast and slow adaptation to balance stability and plasticity. This mechanism has deep roots in neuroscience and biology, but there is no consensus on how to best incorporate it in commonly used optimizers. Here, we show that this can be easily done via the VCL framework, where past posteriors are used as priors in the future. Our key idea is to incorporate slow adaptation via merging of past posteriors to slow down the drift in the knowledge as learning progresses. The merged posterior is then used as the prior in the VCL update to implement the fast-weight updates. These steps can be seamlessly implemented in the IVON optimizer, whose form and costs are nearly identical to that of Adam. We call this new optimizer the Continual IVON (CoVON) optimizer and show that it not only consistently improves over existing VCL optimizers, but also performs better than other weight-regularization strategies across domain-incremental learning, continual pre-training, and fine-tuning of large language models.

14.
arXiv (CS.LG) 2026-06-17

Geodesic Calculus on Implicitly Defined Latent Manifolds

arXiv:2510.09468v3 Announce Type: replace Abstract: Latent manifolds of autoencoders provide low-dimensional representations of data, which can be studied from a geometric perspective. We propose to describe these latent manifolds as implicit submanifolds of some ambient latent space. Based on this, we develop tools for a discrete Riemannian calculus approximating classical geometric operators. These tools are robust against inaccuracies of the implicit representation often occurring in practical examples. To obtain a suitable implicit representation, we propose to learn an approximate projection onto the latent manifold by minimizing a denoising objective. This approach is independent of the underlying autoencoder and supports the use of different Riemannian geometries on the latent manifolds. The framework in particular enables the computation of geodesic paths connecting given end points and shooting geodesics via the Riemannian exponential maps on latent manifolds. We evaluate our approach on various autoencoders trained on synthetic and real data.

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

A Solver-Free Training Method for Predict-then-Optimize

arXiv:2606.19587v1 Announce Type: cross Abstract: We propose a scalable method for training prediction (machine learning) models in the predict-then-optimize paradigm, where model outputs serve as coefficients for a subsequent linear optimization task. Directly minimizing the empirical decision regret is intractable for linear programming and combinatorial optimization since the decision mapping is piecewise constant, and the gradients are zero almost everywhere. While existing methods address this by smoothing the differentiation process, they suffer from scalability issues, since a computationally expensive solver call is required for every gradient evaluation. To address this, we propose a decision-focused learning pipeline based on a measure transformation principle, which yields a new surrogate loss that is completely optimization-solver-free during training. We establish theoretical guarantees, including Fisher consistency and excess risk bounds. Empirically, our method achieves decision quality competitive with state-of-the-art methods while reducing training time by orders of magnitude.

16.
arXiv (CS.CL) 2026-06-24

Sentence-Level Contextual Entrainment in Large Language Models

Contextual entrainment, which is a newly discovered phenomenon in large language models (LLMs), refers to the tendency of a model to assign higher probabilities to tokens that appear in its context. In this work, we extend this phenomenon from the token level to the sentence level by examining the per-token mean log-probability of a sentence instead of the probabilities of individual tokens. We investigate sentence-level contextual entrainment across 26 LLMs from seven families and two datasets, which cover both subjective and objective tasks. We find that sentence-level contextual entrainment exists. This means that the sentences in the prompt (even if they are counterfactual statements) can significantly increase their probability during model inference time. As the model size increases, contextual entrainment gradually decreases. We also find that contextual entrainment is controlled by 2% to 4% of the attention heads. Turning off these attention heads can effectively mitigate contextual entrainment without hurting the model's performance.

17.
PLOS Medicine 2026-05-21

U = U for all: Advancing equity in HIV prevention

by Thiago S. Torres, Paula M. Luz Suppression of HIV with antiretrovirals eliminates HIV transmission risk, summarized as Undetectable = Untransmittable (U = U). However, U = U literacy remains unevenly understood and shared, and stigmas persist. Equitable and accurate awareness of U = U requires culturally tailored interventions, improved provider education, and supportive policy environments beyond biomedical evidence alone. Suppression of HIV with antiretrovirals eliminates HIV transmission risk, summarized as Undetectable = Untransmittable (U=U). However, U=U literacy remains unevenly understood and shared, and stigmas persist. In this Perspective, Thiago Torres and Paula Luz outline what is needed to improve equity and accuracy in global awareness and education of U=U.

19.
arXiv (CS.LG) 2026-06-12

GenAutoML: An Agentic Framework for Dynamic Architecture Generation and Optimization in Time-Series Analysis

arXiv:2606.05860v2 Announce Type: replace Abstract: Designing neural architectures for time-series forecasting and anomaly detection remains a resource-intensive task that often requires substantial domain expertise. Traditional Automated Machine Learning (AutoML) systems typically rely on static, predefined search spaces, limiting their ability to adapt to diverse data characteristics. We present GenAutoML, an agentic framework that leverages Large Language Models (LLMs) as neural architects to bridge natural-language requirements and executable PyTorch implementations. The framework incorporates a Sandboxed Reflection Loop for autonomous code refinement and a Signature-Aware Runtime that enforces architectural consistency and execution safety. To improve robustness under non-stationary conditions, we further introduce a Dynamic Reversible Instance Normalization (Dyn-RevIN) wrapper. Experiments on the ETTh1, ETTm1, and Weather benchmarks demonstrate that GenAutoML can dynamically generate task-specific neural architectures tailored to dataset characteristics. Among the generated models, WaveInterferenceNet achieves inference latency below 0.01 ms per sample while maintaining competitive predictive performance. By emphasizing computational efficiency, architectural adaptability, and stable optimization behavior, GenAutoML enables the creation of ultra-lightweight neural networks suitable for resource-constrained and latency-sensitive Edge AI deployments.

20.
arXiv (CS.CL) 2026-06-19

S2D2: Fast Decoding for Diffusion LLMs via Training-Free Self-Speculation

Block-diffusion language models offer a promising path toward faster-than-autoregressive generation by combining block-wise autoregressive decoding with within-block parallel denoising. However, in the few-step regime needed for practical acceleration, standard confidence-thresholded decoding is often brittle: aggressive thresholds hurt quality, while conservative thresholds require unnecessary denoising steps. Existing approaches that address this issue either require additional training or incur extra test-time compute. We present S2D2, a training-free self-speculative decoding framework for block-diffusion language models. Our key observation is that a block-diffusion model becomes autoregressive when the block size is reduced to one, allowing the same pretrained model to act as both drafter and verifier. S2D2 inserts a speculative verification step into standard block-diffusion decoding and uses lightweight routing policies to decide when verification is worth its cost. This yields a hybrid decoding trajectory in which diffusion proposes tokens in parallel, while the autoregressive mode acts as a local sequence-level critic. Across three mainstream block-diffusion families, S2D2 consistently improves the accuracy-speed tradeoff over strong confidence-thresholding baselines. On SDAR, we observe up to $4.7\times$ speedup over autoregressive decoding, and up to $1.57\times$ over a tuned dynamic decoding baseline while improving accuracy by up to $4.5$ points. On LLaDA2.1-Mini, S2D2 remains complementary to built-in self-correction, including a conservative setting where it is $4.4\times$ faster than the static baseline with slightly higher accuracy.

21.
arXiv (quant-ph) 2026-06-12

Theoretical Study for Generating Optical GKP State via a Single-Photon-Added Squeezed Vacuum

arXiv:2606.12467v1 Announce Type: new Abstract: A theoretical framework is developed to analyze the generation of the optical GKP state using a single-photon-added squeezed vacuum. This state, defined by the squeezing parameter $r$, is injected into a 50:50 beam splitter, and the optical GKP state is obtained through conditional measurement at one output port. The single-photon-added squeezed vacuum is especially prominent in this context because it provides a simpler and more experimentally accessible ingredient than Schrodinger cat states, while conditional measurement ensures projection onto a state that closely approximates the finite-energy GKP form. Fidelity is employed to quantify this closeness, and the analysis demonstrates that the scheme achieves a maximum fidelity of 85% at a squeezing level of $3.76 \ dB$. This performance surpasses approaches based on squeezed optical odd Schrodinger cat states, underscoring the single-photon-added squeezed vacuum as a practical and effective pathway toward fault-tolerant photonic quantum computing.

22.
arXiv (math.PR) 2026-06-11

The Geometry of Admissible Short Selling in Discrete-Time Stochastic Portfolio Theory

arXiv:2606.11191v1 Announce Type: cross Abstract: While discrete-time Stochastic Portfolio Theory (SPT) provides a robust framework for market analysis, existing work on functional generation has predominantly focused on long-only portfolios defined on the entire unit simplex. This paper extends the geometric framework of functional generation to the broader class of bankruptcy-proof long-short portfolios defined on local market state spaces. We establish that, within this admissible setting, pseudo-arbitrage is fully characterized by the concavity of the generating function on the market state space, thereby relaxing the usual global domain requirement. A central contribution of this work is a geometric characterization of the short-selling mechanism. We prove that the presence of short selling is equivalent to the negativity of the maximal concave extension of the generating potential. This phenomenon is linked to the steepness of the logarithmic gradient as the market approaches a zero boundary nested inside the simplex. To systematically exploit this mechanism, we introduce the barycentric scaling transformation, a constructive methodology that maps classical long-only generating functions onto restricted domains to engineer admissible strategies with controlled short-selling exposure. Finally, through the analysis of specific shrunken portfolios, we identify a geometric phase transition: under suitable boundary conditions, admissible strategies exhibit a long-only core and a short-selling region in a qualitative sense (without asserting an exact partition of the state space). This provides a unified geometric perspective on relative arbitrage beyond the long-only constraint.

23.
PLOS Computational Biology 2026-06-02

PepAnno: A structure-aware deep learning framework for bioactive peptide prediction, structural visualization, and physicochemical profiling

Authors:

by Enyan Liu, Yueming Hu, Liya Liu, Yifan Chen, Shilong Zhang, Sida Li, Haoyu Chao, Luyao Xie, Yi Shen, Liangwei Wu, Julio Raúl Fernández Massó, Ming Chen Peptides are gaining prominence as therapeutic candidates due to their diverse physiological functions and structural simplicity. Although multiple computational tools exist for bioactive peptide prediction, many suffer from limitations such as non-intuitive interfaces, sequence-only representations, insufficient structural awareness, restricted interpretability, or fragmented analysis workflows, leading to reduced research efficiency and higher costs. To address these challenges, we present PepAnno (https://bis.zju.edu.cn/pepanno/), a comprehensive and user-friendly web server for multi-functional peptide annotation. PepAnno is powered by a novel structure-aware, multi-view geometric deep learning framework that integrates pre-trained sequence embeddings with predicted 3D structural graphs through a dual-stream architecture combining a Transformer and a GATv2 network. A cross-modal attention mechanism is employed to effectively fuse semantic and geometric representations, enabling accurate multi-task prediction across 7 key bioactivities, including antimicrobial and anticancer properties. Comprehensive evaluation on seven curated bioactivity datasets demonstrates that PepAnno achieves robust and competitive predictive performance across tasks, consistently outperforming or matching existing methods in terms of discrimination and stability. Beyond functional prediction, PepAnno provides automated calculation of physicochemical properties, structure visualization, and access to an integrated repository of peptide-related databases and tools. By enabling one-click peptide annotation, PepAnno offers an efficient and interpretable solution for large-scale peptide analysis and facilitates downstream experimental design and peptide-based drug discovery.

24.
arXiv (CS.AI) 2026-06-11

Sovereign Assurance Boundary: Certificate-Bound Admission for Agentic Infrastructure

arXiv:2606.11632v1 Announce Type: cross Abstract: Agentic infrastructure introduces a critical control-plane authorization problem: non-deterministic reasoning systems can propose high-stakes mutations to production resources, yet existing security mechanisms – such as identity and access management (IAM), policy engines, consensus protocols, and audit logs – either enforce static, context-unaware permissions or merely record actions post-execution. This paper introduces the Sovereign Assurance Boundary (SAB), a certificate-bound runtime admission layer for autonomous execution authority. SAB intercepts agent proposals at an assurance airlock, compiles them into typed execution contracts $C$, and binds these contracts to cryptographic evidence digests $H(E)$ and policy versions. The contracts are then routed through consequence-aware certification paths. Upon successful admission, the system emits a signed Sovereign Assurance Certificate ($\Omega$) that is strictly scoped to a specific execution identity, revocation epoch, and validity window. Finally, a sovereign execution broker verifies $\Omega$ and performs fresh pre-execution revocation and drift checks before invoking infrastructure APIs. We detail the airlock-broker architecture, formalize its admission and revocation invariants, and report preliminary feasibility measurements from a Go prototype evaluated over 2,500 admission attempts. Ultimately, this broker-enforced model prevents autonomous reasoning from directly mutating state, transforming delegated execution authority into a cryptographically verifiable, evidence-bound, revocable, and replayable runtime artifact.

25.
PLOS Medicine 2026-05-27

Sequential chemo-immunotherapy followed by standard versus reduced thoracic radiotherapy for older and/or frail stage III non-small-cell lung cancer: A randomized open-label cohort trial

Authors:

by Wei-Xiang Qi, Shuyan Li, Mengdi Wang, Huan Li, Feifei Xu, Lei Yao, Biao Yu, Linlin Chen, Gang Cai, Cheng Xu, Xianwen Sun, Zhiyao Bao, Jiayi Chen, Yi Xiang, Shengguang Zhao Background The appropriateness of concurrent chemoradiotherapy (cCRT) for older or clinically vulnerable stage III unresectable non-small-cell lung cancer (NSCLC) patients remains contentious. Furthermore, the survival implications of de-escalating thoracic radiotherapy (RT) intensity in this population have not been conclusively elucidated. Methods and findings We conducted a phase II randomized, open-label, two-cohort (non-comparative) trial at a tertiary hospital in China (NCT05557552). Between September 30, 2022 and April 30, 2024, we enrolled 56 older and/or frail patients with stage III NSCLC who were ineligible for cCRT. The primary endpoint was the 1-year progression-free survival (PFS) rate estimated using the Kaplan–Meier method. Secondary endpoints included objective response rate (ORR), overall survival (OS), and safety. In the intention-to-treat (ITT) set, which included all 56 randomized patients who received at least one dose of study treatment, the 1-year PFS was 84.3% (95% confidence interval [CI] [70.3%, 98.3%]) in the standard RT group and 70.7% (95% CI [54.3%, 87.1%]) in the reduced RT group. In the per-protocol set (53 patients), the 1-year PFS was 82.9% (95% CI [68.9%, 98.8%]) in the standard RT group and 73.4% (95% CI [58.3%, 92.4%]), with a median follow-up of 24 months. Among 56 patients in the safety analysis set, 71.4% of patients experienced grade 3/4 adverse events (AEs) in the standard RT group and 53.6% in the reduced RT group. One patient (3.6%) in the reduced RT and three patients (10.7%) in the standardized RT experienced grade 5 AEs. The main limitations are the non-comparative design, small sample size, and lack of power to establish non-inferiority or superiority. Conclusion The current study suggested that reduced RT combined with sequential chemo-immunotherapy might be feasible for older/frail patients intolerant to cCRT, showing numerically similar survival outcomes. These exploratory findings warrant confirmation in larger, adequately powered randomized trials. Trial registration The trial had been registered on ClinicalTrials.gov on Sep 30, 2022.ClinicalTrials.gov NCT05557552