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01.
arXiv (CS.CL) 2026-06-11

Food4All: An Agentic Framework and Benchmark for Food Resource Navigation with Adaptive User Understanding

Food assistance referral requires conversational agents to translate underspecified, often noisy help-seeking dialogues into locally valid resource recommendations. We present Food4All, an agentic food-resource referral framework and benchmark grounded in 686 structured Indiana food resources. Food4All couples a food-specific search tool with 300 multi-turn evaluation tasks spanning single food needs, composite cases with access or document constraints, and five non-ideal user interaction traits: unreasonable demands, rambling responses, impatience, incomplete answers, and inconsistent information. We evaluate six Large Language Models (LLMs) on requirement grounding, resource retrieval, final referral correctness, and interaction efficiency. Although the strongest model achieves 96.33% referral accuracy, our diagnostics reveal persistent failures in grounding schedule, eligibility, intake, and document constraints, as well as failures to preserve valid retrieved resources in the final recommendation. Trait-level analysis further shows that different non-ideal behaviors stress different parts of the referral pipeline. Food4All provides a controlled testbed for studying tool-calling agents in constraint-sensitive food assistance referral under realistic user interaction challenges.

02.
arXiv (quant-ph) 2026-06-11

Exploring Variational Entanglement Hamiltonians

arXiv:2505.10530v3 Announce Type: replace Abstract: Recent advances in analog and digital quantum-simulation platforms have enabled exploration of the spectrum of entanglement Hamiltonians via variational algorithms. In this work we analyze the convergence properties of the variationally obtained solutions and compare them to numerically exact calculations in quantum critical systems. We demonstrate that interpreting the cost functional as an integral permits the deployment of iterative quadrature schemes, thereby reducing the required number of measurements by more than an order of magnitude even in the presence of noise. We further show that a modified ansatz captures deviations from the Bisognano-Wichmann form in lattice models, improves convergence, improves trainability and provides a cost-function-level diagnostic for quantum phase transitions. Finally, we establish that a low cost value does not by itself guarantee convergence in trace distance. Nevertheless, it faithfully reproduces degeneracies and spectral gaps, which are essential for applications to topological phases.

03.
arXiv (CS.AI) 2026-06-12

Otters++: A Time-to-first-spike Based Energy Efficient Optical Spiking Transformer

arXiv:2606.13016v1 Announce Type: new Abstract: Spiking neural networks (SNNs) are promising for energy-efficient inference, and time-to-first-spike (TTFS) coding is especially attractive because each neuron fires at most once. In practice, however, this benefit is often reduced by the cost of computing a temporal decay term and multiplying it by the synaptic weight. We address this issue by turning a physical hardware "bug," the natural signal decay in optoelectronic devices, into the main computation of TTFS, named Otters++. Specifically, we use the measured decay of a custom In$_2$O$_3$ optoelectronic synapse to directly realize the TTFS temporal term, removing the need for explicit digital decay computation. To scale this idea to Transformer models, we establish a layer-wise functional equivalence between the Otters++ and a quantized neural network (QNN), and develop a hybrid training method that uses device-faithful SNN computation in the forward pass and QNN straight-through gradients through the equivalent QNN path in the backward pass, together with model distillation. This avoids differentiation through discrete first-spike events and reduces the over-sparsity problem in direct TTFS-SNN training. We further make training aware of measured device noise by sampling run-to-run variation, and refine the system-level energy model by accounting for device sharing and multi-hop communication. On GLUE dataset, Otters++ improves the average score to 84.17\% while maintaining a clear energy advantage over prior spiking Transformer baselines. These results show that physically grounded TTFS computing can be efficient, trainable, and robust under realistic hardware effects.

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

GMN4AD: Graph Matching Network for Alzheimer's Disease Diagnosis with Test-Time Domain Adaptation using Multi-centered Structure Magnetic Resonance Imaging

Alzheimer's Disease (AD) is a progressive neurodegenerative disorder that affects millions of older adults, with prevalence expected to rise significantly in the coming years. Early diagnosis, particularly during the mild cognitive impairment (MCI) stage, is critical for timely intervention. Structural Magnetic Resonance Imaging (sMRI) has emerged as a key modality for detecting AD-related brain changes, but traditional graph-based approaches often struggle with modality and inter-site heterogeneity, limiting diagnostic performance. In this paper, we propose Graph Matching Network for Alzheimer's Disease Diagnosis (GMN4AD), designed to model interactions between heterogeneous brain graphs derived from neuroimaging data. Unlike conventional methods that treat each brain graph independently, GMN4AD leverages graph matching to capture cross-graph relationships, enhancing diagnostic precision. Furthermore, we introduce a test-time domain adaptation strategy that combines contrastive learning to mitigate domain shifts during inference. Extensive experiments on three public AD datasets demonstrate that GMN4AD achieves superior performance compared to state-of-the-art methods, offering a robust and generalizable solution for AD diagnosis.

05.
arXiv (CS.CL) 2026-06-12

A Survey on Long-Term Memory Security in LLM Agents: Attacks, Defenses, and Governance Across the Memory Lifecycle

The emergence of writable, cross-session persistent memory in LLM agents introduces a qualitatively different threat landscape from conventional input-centric security concerns, characterized by three properties: persistence, statefulness, and propagation. To systematically characterize this landscape, we propose a Memory Lifecycle Framework that organizes attacks, defenses, and their cross-phase dependencies along two axes: six lifecycle phases (Write, Store, Retrieve, Execute, Share & Propagate, Forget & Rollback) and four security objectives (Integrity, Confidentiality, Availability, Governance). This analysis in turn exposes the need for formal security guarantees at the system level, motivating Verifiable Memory Governance(VMG), a framework of five architectural primitives that specifies what verifiable mechanisms a long-term-memory system must provide to maintain auditable, recoverable control over its memory state. Our analysis indicates that robust Long-Term Memory (LTM) security cannot be retrofitted at retrieval or execution time alone, but must be anchored in storage-time provenance, versioning, and policy-aware retention from the outset.

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

ADORE: Iterative Query Expansion with Retrieval-Grounded Relevance Feedback

LLM-based query expansion improves retrieval by enriching the original query with additional context. Yet most methods remain generation-driven, producing plausible pseudo-documents or expansions without checking how the target corpus responds. This can introduce retrieval drift, amplify misleading vocabulary, or miss terms that distinguish relevant from non-relevant documents. We argue that effective expansion requires retrieval-grounded feedback, not just single-pass generation or unverified iteration. We introduce ADORE (ADapt, Observe, Relevance Evaluate), an iterative framework that turns retrieval outcomes into feedback for the next expansion. At each round, an LLM generates pseudo-passages, a retriever exposes the corpus response, and a relevance assessor evaluates retrieved documents against the original query. These judgments identify what to reinforce, what remains undercovered, and what to suppress. Across TREC Deep Learning, BEIR, and BRIGHT, ADORE consistently outperforms strong query expansion baselines with notable improvements across nearly all evaluation settings, improving average nDCG@10 by 24.5% over BM25 and 3.6% over the strongest prior query expansion method on BEIR, and by 122.9% over BM25 and 9.2% over the best query expansion baseline on BRIGHT. Our code and data are publicly available.

07.
arXiv (math.PR) 2026-06-11

Large deviations for marked sparse random graphs with applications to interacting diffusions

arXiv:2204.08789v2 Announce Type: replace Abstract: We consider the empirical neighborhood distribution of marked sparse Erdős-Rényi random graphs, obtained by decorating edges and vertices of a sparse Erdős-Rényi random graph with i.i.d. random elements taking values on Polish spaces. We prove that the empirical neighborhood distribution of this model satisfies a large deviation principle in the framework of local weak convergence. We rely on the concept of BC-entropy introduced by Delgosha and Anantharam~(2019) which is inspired on the previous work by Bordenave and Caputo~(2015). Our main technical contribution is an approximation result that allows one to pass from graph with marks in discrete spaces to marks in general Polish spaces. As an application of the results developed here, we prove a large deviation principle for interacting diffusions driven by gradient evolution and defined on top of sparse Erdős-Rényi random graphs. In particular, our results apply for the stochastic Kuramoto model. We obtain analogous results for the sparse uniform random graph with given number of edges.

08.
arXiv (CS.LG) 2026-06-12

From Parameters to Feature Space: Task Arithmetic for Backdoor Mitigation in Model Merging

arXiv:2606.12498v1 Announce Type: cross Abstract: Model merging (MM) has gained significant attention as a cost-effective approach to integrate multiple task-specific models into a unified model. However, recent work reveals that MM is highly susceptible to backdoor attacks. Existing defenses based on task arithmetic often fail to eliminate backdoors without substantially degrading clean-task performance, owing to their reliance on direct parameter-space editing. To address this gap, we propose Linear Feature Path Minimization (LFPM), a backdoor mitigation framework for model merging, which introduces an anti-backdoor task vector into the backdoored merged model. Unlike prior approaches, LFPM formulates the backdoor robustness of the merged model from a unified feature-space perspective under the Cross-Task Linearity (CTL) framework, which leverages the approximate linearity of features across tasks. This perspective guides the optimization of the anti-backdoor task to suppress backdoors while preserving clean-task performance. Furthermore, we introduce an effective optimization mechanism based on gradient accumulation and loss path-integral, ensuring robust backdoor suppression along the interpolation path. Extensive experiments demonstrate that LFPM consistently exhibits strong robustness against backdoor attacks in both full fine-tuning and Parameter-Efficient Fine-Tuning (PEFT) settings.

09.
arXiv (CS.CL) 2026-06-18

Probing Semantic Alignment, Lexical Invariance, and Syntactic Influence in LLM Metaphor Processing

Large language models (LLMs) achieve strong performance on metaphor detection and interpretation tasks, yet it remains unclear what such behavioral success reveals about metaphor processing. We present a diagnostic analysis that examines the limits of behavioral evidence by probing three complementary dimensions: semantic attribute alignment, lexical invariance, and syntactic sensitivity. Using geometric probing, we assess whether model-generated interpretations align with reference semantic attributes; through context-varying substitution, we analyze the stability of lexical associations between metaphorical and literal expressions; and via controlled syntactic perturbations, we examine sensitivity in metaphor detection. Our analysis reveals that LLM-generated interpretations can exhibit semantic drift relative to reference attributes; stable lexical anchors persist across contextual conditions, potentially supporting conventional metaphors while biasing novel metaphors requiring contextual integration; and detection performance is sensitive to syntactic irregularities. These findings suggest that strong behavioral performance may reflect heterogeneous underlying signals, highlighting the need for caution when interpreting metaphor benchmarks as evidence of robust, integrated semantic understanding.

10.
arXiv (quant-ph) 2026-06-17

Photon anti-bunching in high harmonic generation

arXiv:2606.17620v1 Announce Type: new Abstract: Photon anti-bunching is the direct evidence for the existence of photons without having a classical counterpart. Unlike bunching of photons, which can have a semi-classical description, the effect of photon anti-bunching can only be understood with quantized electromagnetic fields. However, for the process of high harmonic generation (HHG), where many photons of the driving field are upconverted to a single photon of higher energy, there is yet no clear evidence for the presence of individual photon emission. The key result of this work is the prediction of photon anti-bunching in the process of HHG, marking it the first theoretical discovery of non-classicality in the temporal correlations of HHG photons. While other non-classical signatures in HHG, such as sub-Poissonian statistics or squeezing, have been discussed for an ensemble of photons, the anti-bunching signature reported here is a signature of a single photon. This is achieved by using the recently developed Heisenberg picture approach for quantum optical HHG, revealing clear anti-bunching signatures in the intensity correlation function across the entire harmonic spectrum.

11.
arXiv (CS.AI) 2026-06-15

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

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

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

AI4SE and SE4AI Exploration: A Decade Looking Back and Forward

arXiv:2606.19630v1 Announce Type: new Abstract: The March 2020 INCOSE INSIGHT special issue on AI and Systems Engineering (SE) became the most downloaded issue in the publication's history and launched a research community that now draws over 250 registrants to its annual workshop. In this article, we trace the progress in AI and SE across three phases (labeled here foundational, applied, and LLM inflection) based on the authors' reading of the field's core papers, and describe our opinions of where the community has converged and where critical gaps remain. Separately, a human-AI agreement literature review leveraging both human expertise and six AI models was performed to assess the relevance of 1,712 INCOSE INSIGHT articles and 889 SERC publications. The results identify five critical research gaps and offer guidance for practitioners navigating AI adoption, assurance, and workforce transformation in SE. We share the agreement data and the AI4SE/SE4AI Explorer web application so readers can compare their own relevance judgments with the human and AI raters.

13.
medRxiv (Medicine) 2026-06-11

Advancing Clinical Implementation of Cardiovascular Polygenic Risk Scores Through Patient-Level Robustness Assessment

Background and Aims: Polygenic risk scores (PRSs) for atherosclerotic cardiovascular disease (ASCVD) can perform equivalently at the population level yet disagree for individual patients. We examined whether such intra-individual variability reflects genuinely complementary risk information or mainly statistical and methodological uncertainty, and whether it affects clinical classification once PRSs are integrated into SCORE2-OP. Methods: In 4,137 ASCVD-free participants of the CoLaus|PsyCoLaus cohort (478 incident events over a median 14.4 years), we identified 16 ASCVD-PRSs with practically equivalent population-level performance using Bayesian equivalence testing. We quantified intra-individual variability (standard deviation, coefficient of variation, intraclass correlation, Cohen's kappa, extreme discordance), tested whether discordance exceeded chance, decomposed scores into shared and unique genetic components, and assessed variability after integration into SCORE2-OP, benchmarked against perturbation of systolic blood pressure. Results: For a typical individual, risk estimates varied by 18 percentile points across PRSs. Discordance matched chance expectations under a shared-signal model, with no distinct phenotypic profile among discordant individuals, and predictive power resided overwhelmingly in the shared genetic component. Variability tracked PRS size and weighting rather than distinct variants. After integration into SCORE2-OP, 75.6% of participants were placed in different categories by at least one model and 54.6% as both low and high risk; instability was concentrated near guideline thresholds and far exceeded that from blood-pressure measurement error. Conclusions: Equivalent population-level performance is not sufficient to treat PRSs as interchangeable at the individual level, and methodological standardisation and pragmatic clinical trials remain necessary to determine whether PRS integration improves long-term cardiovascular outcomes.

14.
arXiv (CS.CL) 2026-06-19

A Layered Security Framework Against Prompt Injection in RAG-Based Chatbots

Prompt injection is ranked as the most critical vulnerability in large language model (LLM) deployments by the OWASP Top 10 for LLM Applications, yet existing defenses operate at isolated pipeline stages and remain incomplete. Input filters cannot inspect retrieved documents, while output monitors cannot prevent malicious payloads from reaching the model. Consequently, retrieval-augmented generation (RAG) chatbots remain vulnerable to indirect injection, where a poisoned knowledge-base document compromises every user whose query retrieves it. We present a three-layer framework that intercepts both direct and indirect prompt injection throughout the inference pipeline. Layer 1 screens user input using a rule-based pattern library and a fine-tuned semantic anomaly classifier. Layer 2 enforces a provenance-based instruction hierarchy during context assembly, preventing retrieved content from overriding operator policy. Layer 3 audits model output using a policy rule engine and semantic drift detector before delivery. A continuous audit loop aggregates structured logs and supports retraining to adapt the classifier to emerging attack patterns. The framework is model-agnostic and deploys as middleware without modifying the underlying LLM. Evaluation on 5,080 samples across GPT-4o, Llama 3, and Mistral 7B shows that the framework reduces Attack Success Rate (ASR) from 71.4\% to 11.3\%, outperforming the best single-layer baseline by 27.3 percentage points and a published guardrail system by 23.8 percentage points, while maintaining a 4.8\% false positive rate and a median latency overhead of 61.2 ms. Ablation studies confirm that all three layers provide complementary protection and that their combined effect exceeds the sum of individual contributions.

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

Convex Approximation of Two-Layer ReLU Networks for Hidden State Differential Privacy

arXiv:2407.04884v4 Announce Type: replace Abstract: The hidden state threat model of differential privacy (DP) assumes that the adversary has access only to the final trained machine learning (ML) model, without seeing intermediate states during training. However, the current privacy analyses under this model are restricted to convex optimization problems, reducing their applicability to multi-layer neural networks, which are essential in modern deep learning applications. Notably, the most successful applications of the hidden state privacy analyses in classification tasks have only been for logistic regression models. We demonstrate that it is possible to privately train convex problems with privacy-utility trade-offs comparable to those of 2-layer ReLU networks trained with DP stochastic gradient descent (DP-SGD). This is achieved through a stochastic approximation of a dual formulation of the ReLU minimization problem, resulting in a strongly convex problem. This enables the use of existing hidden state privacy analyses and provides accurate privacy bounds also for the noisy cyclic mini-batch gradient descent (NoisyCGD) method with fixed disjoint mini-batches. Empirical results on benchmark classification tasks demonstrate that NoisyCGD can achieve privacy-utility trade-offs on par with DP-SGD applied to 2-layer ReLU networks.

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

EffGen: Enabling Small Language Models as Capable Autonomous Agents

Most existing language model agentic systems today are built and optimized for large language models (e.g., GPT, Claude, Gemini) via API calls; while powerful, this approach faces several limitations including high token costs and privacy concerns for sensitive applications. We introduce EffGen, an open-source agentic framework optimized for small language models (SLMs) that enables effective, efficient, and secure local deployment. EffGen makes four major contributions: (1) Enhanced tool-calling with prompt optimization that compresses input prompts by up to 70-80% (and 57% on average across our benchmarks) while preserving task semantics, (2) Intelligent task decomposition that breaks complex queries into parallel or sequential subtasks based on dependencies, (3) Complexity-based routing using five factors to make smart pre-execution decisions, and (4) Unified memory system combining short-term, long-term, and vector-based storage. Additionally, EffGen unifies multiple agent protocols (MCP, A2A, ACP) for cross-protocol communication. Results on 13 benchmarks show EffGen outperforms LangChain, AutoGen, and Smolagents with higher success rates, faster execution, and lower memory. Our results reveal that prompt optimization and complexity routing have complementary scaling behavior: optimization benefits SLMs more (11.2% gain at 1.5B vs 2.4% at 32B), while routing benefits large models more (3.6% at 1.5B vs 7.9% at 32B), providing consistent gains across all scales when combined. EffGen is released under the Apache 2.0 License, ensuring broad accessibility for research and commercial use, with the code available at https://github.com/ctrl-gaurav/effGen, the Python package at https://pypi.org/project/effgen/ (pip install effgen), and the project website and documentation at https://effgen.org/ and https://docs.effgen.org/.

17.
arXiv (CS.CV) 2026-06-19

SSD: Spatially Speculative Decoding Accelerates Autoregressive Image Generation

Autoregressive models excel in visual generation by treating images as 1D sequences of discrete tokens, mirroring language modeling. However, this flattening discards the intrinsic 2D spatial locality of visual signals, creating severe computational bottlenecks during inference. We introduce Spatially Speculative Decoding (SSD), a framework that aligns the predictive objective with the natural geometry of images. Rather than predicting only the immediate next token in a 1D sequence, our model simultaneously predicts the adjacent horizontal token and the token directly below it. By capitalizing on this 2D spatial correlation, spatially speculative decoding overcomes the memory wall in visual inference. Our approach accelerates autoregressive image generation by up to 13.3x while maintaining high fidelity on DPG-Bench and GenEval. Our results suggest that respecting the underlying geometry of vision unlocks massive computational efficiencies, paving the way for real-time, high-resolution autoregressive generative models.

18.
arXiv (quant-ph) 2026-06-12

Continuum Neural Momentum Eigenstate for Variationally Solving Quasiparticles

arXiv:2606.12928v1 Announce Type: cross Abstract: We design the first neural quantum state for continuum particles that, for any chosen allowed momentum $\mathbf{k}$, is by construction an exact eigenstate of total momentum with eigenvalue $\mathbf{k}$. Our architecture, EVE, enables off-the-shelf VMC to solve for momentum-sector ground states. We test EVE on 2D bosons with mutual $1/r$ interactions, finding that a single unified ansatz is capable of describing four qualitatively different states: superfluid, roton, crystal, and phonon. At different densities, we extract the underlying phase of matter from the dispersion's shape. At $r_s = 20.0$, we see the roton minimum at finite $k$ expected of a superfluid. At $r_s = 100.0$, we see striking zone folding indicative of crystalline order, with periodically spaced minima representing floating crystals connected by phonon arcs in between. Using density-density correlation functions, we confirm the phase diagnoses and probe the excitations' correlation structures. Finally, we analyze the roton's phase texture and find unexpected multi-particle phase strings, formed when several vortex dipoles merge, leaving two vortices connected by a phase slip.

19.
arXiv (CS.LG) 2026-06-17

Can Vision Foundation Models Navigate? Zero-Shot Real-World Evaluation and Lessons Learned

arXiv:2603.25937v2 Announce Type: replace-cross Abstract: Visual Navigation Models (VNMs) promise generalizable, robot navigation by learning from large-scale visual demonstrations. Despite growing real-world deployment, existing evaluations rely almost exclusively on success rate, whether the robot reaches its goal, which conceals trajectory quality, collision behavior, and robustness to environmental change. We present a real-world evaluation of five state-of-the-art VNMs (GNM, ViNT, NoMaD, NaviBridger, and CrossFormer) across two robot platforms and five environments spanning indoor and outdoor settings. Beyond success rate, we combine path-based metrics with vision-based goal-recognition scores and assess robustness through controlled image perturbations (motion blur, sunflare). Our analysis uncovers three systematic limitations: (a) even architecturally sophisticated diffusion and transformer-based models exhibit frequent collisions, indicating limited geometric understanding; (b) models fail to discriminate between different locations that are perceptually similar, however some semantics differences are present, causing goal prediction errors in repetitive environments; and (c) performance degrades under distribution shift. We will publicly release our evaluation codebase and dataset to facilitate reproducible benchmarking of VNMs.

20.
arXiv (quant-ph) 2026-06-11

Mathematical Basis for Analyzing Superconducting Phase Transitions Using Catastrophe Theory

arXiv:2606.11810v1 Announce Type: cross Abstract: We establish a rigorous mathematical bridge from quantum many-body path integrals to the cusp catastrophe model by Lyapunov-Schmidt reduction, which provides a theoretical foundation for analyzing superconducting phase transition using the catastrophe theory. First, it is proved that, near the critical point the infinite-dimensional effective action is diffeomorphic to a finite-dimensional catastrophe. Secondly, starting from Ginzburg-Landau free energy functional, the Euler-Lagrange partial differential equation can be reduced to the cusp catastrophe model. Thirdly, the fermionic imaginary-time path integral to the cusp catastrophe is derived through the Hubbard-Stratonovich transformation, Matsubara frequency expansion, and Grassmann algebra. Furthermore, we connect this framework with the adsorption potential theory we proposed, elucidating the catastrophic topological nature of the electron pairing mechanism in high-temperature superconductivity. The precise microscopic derivation of the adsorption potential from first-principles electronic structure calculations would strengthen the predictive power of the theory.

21.
Nature (Science) 2026-06-10

Molecular glue degraders of HuR suppress BRAF-mutant colorectal cancer

作者:

BRAF gain-of-function mutations, particularly BRAF(V600E), affect roughly 10% of all patients with colorectal cancer (CRC), and portend poor prognosis with limited therapeutic interventions. BRAF inhibitors such as encorafenib are ineffective due to MAPK pathway reactivation driven by BRAF dimerization. Combined inhibition of BRAF and EGFR, although approved therapies, results in short survival benefits and frequent treatment resistance and relapse1–3. Here, through rational chemical library design coupled with parallel proteomic screening, we identified dHuR as a molecular glue degrader of human antigen R (HuR), an RNA-binding protein that drives tumour growth, invasion and therapy resistance. dHuR binds to the CRBN ubiquitin ligase to create a unique benzofuran-tethered composite surface to recruit HuR as a neosubstrate by engaging its β-hairpin G-loop degron, as revealed by the cryo-electron microscopy structure of the ternary complex. dHuR abrogated BRAF expression by inducing its exon 18 skipping, and demonstrated superior suppression of BRAF-mutant CRC tumours including those gaining resistance to BRAF inhibitors. Finally, we performed kinome library CRISPR screening and revealed that inactivation of EGFR or MEK enhanced dHuR cytotoxicity, thus establishing a combinatorial strategy to treat patients with refractory BRAF-mutant CRC. Molecular glue degraders of the RNA-binding protein HuR have therapeutic potential for BRAF-mutant cancers.

22.
arXiv (CS.LG) 2026-06-15

Arbitrary control over multimode wave propagation for machine learning

arXiv:2402.17750v2 Announce Type: replace-cross Abstract: Controlled multimode wave propagation can enable more space-efficient photonic processors than architectures based on discrete components connected by single-mode waveguides. Instead of defining discrete elements, one can sculpt the continuous substrate of a photonic processor to perform computations through multimode interference in two dimensions. Here we designed and demonstrated a device with a refractive index that can be rapidly reprogrammed across space, allowing arbitrary control of wave propagation. The device, a two-dimensional programmable waveguide, uses parallel electro-optic modulation of the refractive index of a slab waveguide with about $10^4$ programmable spatial degrees of freedom. We implemented neural network inference on benchmark tasks with up to $49$-dimensional vectors in a single pass, without digital pre-processing or post-processing. Theoretical and numerical analyses further indicated that two-dimensional programmable waveguides may offer not only a constant-factor reduction in device area but also a scaling benefit, with the area required growing as $N^{1.5}$ rather than $N^2$.

23.
arXiv (CS.LG) 2026-06-11

Scaling Laws of Global Weather Models

arXiv:2602.22962v2 Announce Type: replace Abstract: Data-driven models are revolutionizing weather forecasting. To optimize training efficiency and model performance, this paper analyzes empirical scaling laws within this domain. We investigate the relationship between model performance (validation loss) and three key factors: model size ($N$), dataset size ($D$), and compute budget ($C$). Across a range of models, we find that Aurora exhibits the strongest data-scaling behavior: increasing the training dataset by 10x reduces validation loss by up to 3.2x. GraphCast demonstrates the highest parameter efficiency, yet suffers from limited hardware utilization. Our compute-optimal analysis indicates that, under fixed compute budgets, allocating resources to more total training data yields greater performance gains than increasing model size. Furthermore, we analyze model shape and uncover scaling behaviors that differ fundamentally from those observed in language models: weather forecasting models consistently favor increased width over depth. These findings suggest that future weather models should prioritize wider architectures and larger effective training datasets to maximize predictive performance.

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

Sobolev Approximation by Fixed-Size Neural Networks with Arbitrary Accuracy

arXiv:2606.16975v1 Announce Type: cross Abstract: In this work, we investigate new activation functions for achieving arbitrary-accuracy Sobolev approximation by fixed-size neural networks. We first show that any function in $W^{2,\infty}((a,b)^d)$ can be approximated with arbitrary accuracy, measured in the $W^{1,\infty}$-norm, by a fixed-size neural network using the Elementary Universal Activation Function ($\mathrm{EUAF}$). To extend this result to $W^{s,\infty}((a,b)^d)$ for $s\in\mathbb{N}$, we introduce a smooth activation $\mathrm{DUAF}_{\infty}$ from the family of Differentiable Universal Activation Functions ($\mathrm{DUAF}_n$). We prove that any function in $W^{s,\infty}((a,b)^d)$ can be approximated with arbitrary accuracy in the $W^{s-1,\infty}$-norm by a fixed-size $\mathrm{DUAF}_{\infty}$-activated network. We further construct sigmoidal variants $\widetilde{\mathrm{DUAF}}_n$ and show that, for every $1\leq s\leq n$, fixed-size $\widetilde{\mathrm{DUAF}}_n$-activated networks still approximate any $f\in W^{s,\infty}((a,b)^d)$ with arbitrary accuracy in the $W^{s-1,\infty}$-norm. In all these results, the width and depth bounds are computed explicitly, and the proposed activations are elementary.

25.
arXiv (quant-ph) 2026-06-17

A Quantum Approach to Stochastic Optimization in Insurance Underwriting

arXiv:2605.01169v2 Announce Type: replace Abstract: The presence of stochastic elements in combinatorial optimization problems makes them particularly challenging, as such problems quickly become intractable for classical computers even at relatively small sizes. In this work, we propose a novel quantum-classical hybrid scheme for solving a class of stochastic optimization problems known as chance-constrained knapsack problems, in which item weights follow probability distributions and constraints may be violated within a specified risk tolerance. Our method employs knapsack-specific QAOA-based circuits to generate samples which, when combined with a new self-consistent classical recovery scheme introduced in this work, produce high-quality solutions. Experiments carried out on IBM Heron processors, using circuits with depths up to 177 and comprising 3443 gates acting on as many as 150 qubits, yield solutions that indicate performance comparable to classical optimization schemes. The proposed quantum-classical scheme paves the way to tackling such problems, with the potential to outperform approaches that rely solely on classical computation.