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01.
bioRxiv (Bioinfo) 2026-06-14

TopoMIL: Topology Improves Multiple Instance Learning in Diagnostic Microscopic Images

Microscopic images of cells and tissues are central to disease diagnosis. In computational pathology, multiple instance learning (MIL) has emerged as a key paradigm for analyzing numerous images within a single patient sample. While the representative distribution of cells in a sample is important for diagnosis, existing MIL frameworks largely overlook it. We introduce TopoMIL, a framework that extracts the representative topological structure of the sample and integrates it into the MIL classifier. Three topological representations are assessed, each with distinct advantages and computational costs. We evaluate TopoMIL on four histopathology and cytomorphology datasets, each presenting unique challenges. Integrating the sample's topological information into MIL enhances classification across average, max, attention-based, and transformer pooling, yielding AUCROC gains of 3.3%, 4.2%, 5.9%, and 0.5%, respectively, with moderate computational cost. Our work underscores the potential of TopoMIL as a scalable extension to existing morphology-based models in computational pathology.

02.
arXiv (CS.CL) 2026-06-19

Your Mouse and Eyes Secretly Leak Your Preference: LLM Alignment using Implicit Feedback from Users

To align a Large Language Model (LLM), most existing methods collect explicit human feedback and train a reward model to predict the human preference based on the response text. These existing methods have two key limitations. First, the users rarely provide explicit feedback for LLM responses, which makes the high-quality preference annotation expensive to collect. Second, the methods do not leverage implicit human feedback, which has proven vital to the economic moats of Internet giants. To quantify the value of implicit feedback, we build a new dataset called IFLLM, which collects 1336 multi-turn questions from the 59 Mechanical Turk workers, their mouse trajectories, and eye gazing points to the LLMs' responses from their webcams. IFLLM shows that the users have very diverse types of gazing behavior and mouse trajectories. Our reward model based on the implicit user feedback boosts the accuracy of the text-based reward model from 55% to 64% and nearly triples the relative response quality improvements after applying the DPO to eight LLMs, demonstrating the value of implicit feedback in the wild. Our data collection website, dataset, and codes can be found at https://github.com/themehulpatwari/llm-implicit-feedback/.

03.
arXiv (quant-ph) 2026-06-19

Optimal multi-spectral squeezing via deterministic 2D-phase optimization

arXiv:2606.20192v1 Announce Type: new Abstract: Optimization routines are ubiquitous in quantum information technologies and essential to reach the resource levels required by quantum protocols. Specifically, multi-spectral squeezing for use in such protocols requires that losses be kept minimal at every stage, including coherent detection, which is performed by interfering the signal with a classical local-oscillator beam. This in turn requires control over all optical degrees of freedom of the beam in order to optimize the detection. The most general framework for this optimization relies on agnostic, off-the-shelf machine-learning techniques. Here we take the opposite approach: by focusing on a physical description of the specific optical process, we develop a deterministic sequential algorithm that provably reaches the global maximum of the visibility in a pixel basis and scales linearly with the number of pixels, thereby offering an efficient and theoretically grounded alternative to black-box optimization. In our waveguide-based setup, the optimized mask increases the visibility from 76% to 84%, corresponding to a 20% gain in mode-matching efficiency. Multi-spectral squeezing measurements confirm that this improvement translates directly into quantum readout: for the most squeezed spectral mode, the squeezing increases from $-2.08$ dB to $-2.64$ dB, consistent with the inferred efficiency gain. These results establish deterministic spatial phase shaping as an effective, interpretable route to enhanced multimode squeezing in waveguide platforms.

05.
bioRxiv (Bioinfo) 2026-06-08

TRACEY: an updated resource for SNARE protein domain annotation with improved HMMs and expanded sequence coverage

Motivation: SNARE proteins catalyse membrane fusion across the eukaryotic endomembrane system, from synaptic vesicle exocytosis to intracellular trafficking, endosomal and vacuolar transport, and autophagy, and their accurate domain annotation depends on the quality of profile models and the sequence diversity behind them. The original SNARE domain classification predates the recent expansion of eukaryotic sequence data, leaving its HMM profiles and subgroup coverage unable to resolve divergent and lineage-specific paralogs. Results: We present an updated release of TRACEY built on a resynchronized, non-redundant collection of 18,915 curated SNARE proteins spanning 1,188 species, together with a consolidated set of 83 HMM profiles, including 43 models for newly defined subgroups, reconstructed through an iterative, mixture-model-driven procedure. In direct comparison with the legacy models, at least ~75% of sequences in every overlapping group scored better with the new HMMs, indicating systematic gains in domain detection. A redesigned web interface adds multiparameter querying, FASTA download, and direct scanning of user-submitted sequences against the curated profiles. Availability and implementation: TRACEY is freely available at https://tracey.unil.ch.

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

SwitchBraidNet: Quantisation-Aware Lightweight Architecture for Hybrid Brain-Computer Interface

arXiv:2606.18816v1 Announce Type: cross Abstract: Hybrid brain-computer interfaces (BCIs) that integrate motor imagery (MI) and steady-state visual evoked potentials (SSVEP) provide high-dimensional neural decoding but typically exceed the computational limits of embedded hardware. To address this, we propose SwitchBraidNet, a compact EEG classification architecture designed for low-power deployment. The model employs a dual-path temporal braid to extract multiscale oscillatory features, an adaptive squeeze-and-excitation spatial switch for electrode gating, and a log-variance readout layer for direct band-power encoding. Furthermore, through systematic quantisation-aware training on the OpenBMI dataset, we compared SwitchBraidNet against four established baselines across FP32, FP16, and INT8 precisions. Experimental results demonstrate superior efficiency and performance, achieving MI accuracy of 69.49% (FP16), SSVEP accuracy of 93.48% (FP32), and a hybrid information transfer rate of 64.82 bits/min (FP16). With an INT8 footprint of only 3.03 KB, SwitchBraidNet maintains high accuracy across varying numerical precisions, demonstrating its suitability for low-power embedded BCI deployment.

07.
arXiv (CS.AI) 2026-06-19

ScaffoldAgent: Utility-Guided Dynamic Outline Optimization for Open-Ended Deep Research

arXiv:2606.20122v1 Announce Type: new Abstract: Open-ended deep research (OEDR) requires systems to acquire knowledge through multi-round retrieval and generate coherent long-form reports. The outline plays a central role as a structural scaffold that coordinates retrieval, evidence organization, and generation. However, existing methods either fix the outline before writing or refine it with local heuristics, leading to scaffold drift under continuous information accumulation and delayed feedback for evaluating outline modifications. We propose ScaffoldAgent, a utility-guided dynamic outline optimization framework for OEDR. ScaffoldAgent models outline evolution as a structured decision process with three operations: Expansion, Contraction, and Revision, enabling controlled updates to the report scaffold. It further introduces a utility-guided feedback mechanism that estimates the downstream value of each outline operation from retrieval gain, structural coherence, and trial-generation quality. The resulting utility signal guides node selection, operation scheduling, and termination during inference. Experiments on DeepResearch Bench and DeepResearch Gym show that ScaffoldAgent consistently improves long-form report generation and factual grounding over existing deep research agents.

08.
medRxiv (Medicine) 2026-06-15

Recruitment, Retention Approaches and Community Engagement in the THRIVE pilot Trial: Lessons Learned from a Food is Medicine Trial

Background: Recruitment of underrepresented populations, including Black and Hispanic populations, for Food is Medicine (FIM) and cardiovascular trials, may pose significant challenges. Methods: We implemented a multi-component recruitment approach for the THRIVE (AdapTive personalized dietitian coacHing and messaging with pRoduce prescrIptions to improVE healthy dietary behaviors) pilot trial to engage primarily Black and Hispanic adults in a Food is Medicine for hypertension intervention. The recruitment approaches included community engagement at approximately 40 community events (cultural festivals and neighborhood gatherings); partnerships with 8 community and faith-based service hubs and food distribution sites; recruitment through safety net primary care clinics, digital outreach via the study website, and social media campaigns; and direct recruitment at places of worship. We report lessons learned from the community engagement process, recruitment efficiency, representativeness, and retention outcomes. Results: Within 6 months, the enrollment target was exceeded by 40%, with an accrual index of 1.04. Over 1,000 individuals were reached through the direct-to-community engagement process, while faith-based partnerships engaged about 900 adults. There were 2,673 visits to the study webpage, and social media achieved 12,259 impressions with 399 clicks. About 95% of participants resided within 10 miles of the faith-based recruitment sites. Face-to-face engagement at the food distribution sites within faith-based organizations or community service hubs outperformed digital methods. Faith leader endorsements and follow-up in-person meetings (following unsuccessful email outreach) dramatically increased recruitment. Regarding retention, pre-randomization attrition was 6%, and 82% of participants completed the study. Conclusion: Culturally tailored, community-engaged recruitment grounded in faith-based and local community partnerships, was highly effective in engaging Black and Hispanic populations in this FIM cardiovascular trial. This provides a replicable model for implementing equitable and sustainable cardiovascular health interventions.

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

ForecastBench-Sim: A Simulated-World Forecasting Benchmark

Forecasting benchmarks for general-purpose AI systems usually inherit the constraints of the real world: outcomes resolve slowly, tail events are rare, and counterfactual questions are difficult to score. We introduce ForecastBench-Sim, a simulated-world forecasting benchmark built on game rollouts from Freeciv, a turn-based strategy game modelled on the Civilization series. Forecasters receive a fixed world report (a structured snapshot of the current game state) and answer questions about hidden future states; the benchmark then continues the simulation and scores forecasts. Because the world is simulated, the same setup can generate continuous or binary forecasting questions at arbitrary time horizons, paired intervention worlds for conditional or causal questions, and resolved examples of rare or disruptive outcomes. We describe the benchmark pipeline, question families, scoring protocol, and release artifacts, and report validation slices from model evaluations and an anonymized human pilot. ForecastBench-Sim is intended to complement real-world forecasting benchmarks by providing controlled, immediately resolvable tasks for studying probabilistic reasoning under dynamic world states.

10.
arXiv (CS.LG) 2026-06-11

Mechanisms of Introspective Awareness

arXiv:2603.21396v5 Announce Type: replace Abstract: Recent work has shown that LLMs can sometimes detect when steering vectors are injected into their residual stream and identify the injected concept – a phenomenon termed "introspective awareness." We investigate the mechanisms underlying this capability in open-weights models. First, we find that it is behaviorally robust: models detect injected steering vectors at moderate rates with 0% false positives across diverse prompts and dialogue formats. Notably, this capability emerges specifically from post-training; we show that preference optimization algorithms like DPO can elicit it, but standard supervised finetuning does not. We provide evidence that detection cannot be explained by simple linear association between certain steering vectors and directions promoting affirmative responses. We trace the detection mechanism to a two-stage circuit in which "evidence carrier" features in early post-injection layers detect perturbations monotonically along diverse directions, suppressing downstream "gate" features that implement a default negative response. This circuit is absent in base models and robust to refusal ablation. Identification of injected concepts relies on largely distinct later-layer mechanisms that only weakly overlap with those involved in detection. Finally, we show that introspective capability is substantially underelicited: ablating refusal directions improves detection by +53%, and a trained bias vector improves it by +75% on held-out concepts, both without meaningfully increasing false positives. Our results suggest that this introspective awareness of injected concepts is robust and mechanistically nontrivial, and could be substantially amplified in future models. Code: https://github.com/safety-research/introspection-mechanisms.

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

The ASE-LSE Disagreement Landscape: An End-to-End Characterisation of Extremes and Structural Drivers

arXiv:2605.22346v3 Announce Type: replace-cross Abstract: Two of the most widely used methods for analysing graph data, Adjacency Spectral Embedding and Laplacian Spectral Embedding, often produce different results when applied to the same graph. Yet the structural reasons behind this disagreement remain incompletely understood. This paper provides an end-to-end account of ASE-LSE latent subspace disagreement. We first prove that the two methods produce identical latent subspaces for every embedding dimension whenever the Laplacian is a scalar multiple of the adjacency matrix, and show that this scalar relationship holds if and only if the graph is either regular or bipartite biregular. This anchor result identifies a sufficient condition for perfect agreement that pins down the floor of the disagreement spectrum and supplies the baseline for the perturbation analysis. We then prove that no maximal-disagreement graph or family of graphs exists: the disagreement is always strictly below its theoretical ceiling, and we exhibit a witness family demonstrating that no finite maximum is attainable, so the disagreement landscape has no maximiser. With both endpoints established, we derive a Regularity Departure Bound whose two terms isolate degree heterogeneity and eigengap as the primary structural factors influencing disagreement in the middle regime. Empirical validation across thousands of simulated graphs confirms the mechanisms predicted by the bound: heterogeneity pushes disagreement up, eigengap suppresses it, and their joint ratio emerges as a unified predictor of ASE-LSE disagreement, suggesting when the two embeddings can be treated as interchangeable and when they cannot.

12.
arXiv (CS.CV) 2026-06-17

Theoretical Grounding of Out-Of-Distribution Detection With Reinforcement Learning Optimizer

Out-of-distribution (OOD) detection in dynamic open-world environments requires a model to continually adapt to evolving data distributions while generalizing to covariate-shifted inputs and rejecting semantic-shifted OOD examples. Most existing OOD detection methods optimize only the current-step objective and do not explicitly account for how post-deployment environment changes affect future OOD behavior. In this paper, we establish a theoretical grounding for dynamic OOD detection using a reinforcement learning (RL)-guided optimizer that explicitly favors updates that reduce the semantic OOD false positive rate over time. We develop a novel augmented optimizer that uses an RL-guided correction term on top of standard gradient descent (GD) and show its improvement over both future-domain generalization and semantic-OOD rejection. We analyze temporal error decomposition in terms of model-change and environment-change generalization errors and develop a new theoretical framework for comparing the generalization errors under both GD and RL-guided optimizers.

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

Graph Regularized Non-negative Reduced Biquaternion Matrix Factorization for Color Image Recognition

Non-negative reduced biquaternion matrix factorization (NRBMF) uses the product of reduced biquaternion (RB) matrices to incorporate the non-negativity constraints of color image pixels into the factorization process. However, NRBMF mainly focuses on reconstruction accuracy and does not explicitly exploit the local geometric structure of image data, which may limit the discriminative ability of the obtained low-dimensional coefficient representations. To address this issue, we propose a graph regularized non-negative reduced biquaternion matrix factorization (GNRBMF) model for color image recognition. The proposed model incorporates a graph Laplacian regularizer into the reduced biquaternion coefficient matrix, encouraging nearby samples in the original space to have similar coefficient representations. Meanwhile, GNRBMF retains the non-negativity property of NRBMF in the reduced biquaternion algebra. To solve the optimization problem, a component-wise alternating projected gradient algorithm is derived, and its convergence properties are analyzed. Experimental results on three color image datasets show that the proposed GNRBMF model achieves competitive or superior recognition performance compared with several methods in most tested settings.

14.
arXiv (CS.AI) 2026-06-11

Bimanual Robot Manipulation via Multi-Agent In-Context Learning

arXiv:2604.20348v2 Announce Type: replace-cross Abstract: Language Models (LLMs) have emerged as powerful reasoning engines for embodied control. In particular, In-Context Learning (ICL) enables off-the-shelf, text-only LLMs to predict robot actions without any task-specific training while preserving their generalization capabilities. Applying ICL to bimanual manipulation remains challenging as the high-dimensional joint action space and tight inter-arm coordination constraints rapidly overwhelm standard context windows. To address this, we introduce BiCICLe (Bimanual Coordinated In-Context Learning), the first framework that enables standard LLMs to perform few-shot bimanual manipulation without fine-tuning. BiCICLe frames bimanual control as a multi-agent leader-follower problem, decoupling the action space into sequential, conditioned single-arm predictions. Evaluated on 13 tasks from the TWIN benchmark, BiCICLe achieves 70.5% average success rate, outperforming the best training-free baseline by 6.1 percentage points and surpassing most supervised methods. We also demonstrate superior real-world performance on 3 tasks without hardware-specific retraining.

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

The algebra of Krom logic programs

arXiv:2606.15719v1 Announce Type: cross Abstract: This paper investigates the algebraic structure of Krom logic programs, consisting only of facts and rules with at most one body atom. We show that sequential composition endows the class of Krom programs with a natural monoid structure and that this structure admits rich algebraic extensions to Krom seminearrings, Krom quemirings, Krom-Conway seminearrings, and Krom-Conway omegaseminearrings. Furthermore, we establish explicit generating sets and canonical decompositions, study the associated ${}^\omega$-operator, characterize the Kleene star in graph-theoretic terms, and relate finite Krom monoids to transformation monoids and finite-state automata. These results provide new connections between logic programming, algebraic automata theory, and algebraic graph theory.

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

FitText: Evolving Agent Tool Ecologies via Memetic Retrieval

arXiv:2605.02411v2 Announce Type: replace Abstract: A semantic gap separates how users describe tasks from how tools are documented. As API ecosystems scale to tens of thousands of endpoints, static retrieval from the initial query alone cannot bridge this gap: the agent's understanding of what it needs evolves during execution, but its tool set does not. We identify this retrieval interface, not planning, as the binding constraint on end-to-end agent performance, and introduce FitText, a training-free framework that makes retrieval dynamic by embedding it directly in the agent's reasoning loop. FitText treats retrieval as test-time evolution of hypotheses: the agent generates natural-language pseudo-tool descriptions (revisable beliefs about the tool it needs), refines them iteratively using retrieval feedback, and explores diverse alternatives through stochastic generation. Memetic Retrieval adds evolutionary selection pressure over candidate descriptions, guided by a tool memory that avoids redundant search. On ToolRet (three domains), FitText's reformulation strategies improve NDCG@5 by 2.7 to 10.6 points over static query retrieval across all base models; on StableToolBench (16,464 APIs) with GPT-5.4-mini, Memetic reaches an 84.3% pooled pass rate, a 26.7-point absolute gain over static query retrieval.

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

Skill-Constrained Model Predictive Control for Resilient Manufacturing Supply Chains

arXiv:2606.17269v1 Announce Type: new Abstract: In skill-constrained production-inventory systems, the qualified human capacity available tomorrow depends on training decisions made today: production requires certified workers, certifications decay unless maintained, and training consumes the same scarce worker hours that production needs now. We study a closed-loop skill-constrained model predictive controller that, at every shift, solves a finite-horizon mixed-integer program over production, inventory, backlog, and training, with binary predicted certification, hard production eligibility, and an interpretable terminal value that prices certified-capacity gaps at the horizon boundary; only the first-period action is applied before replanning. On synthetic, seed-controlled SkillChain-Gym scenarios - announced and surprise new-skill shocks, demand shocks, absenteeism, forecast- and availability-quality modes, capacity-boundary and training-rate sweeps, and negative controls - we evaluate the controller against production-only and maintenance-only ablations, static cross-training insurance plans, and a strong reactive heuristic, under an ex-ante locked configuration and paired statistics. The result is regime dependence, not superiority: no policy class dominates. Predictive control helps when skill or labor bottlenecks are forecastable early enough for training to complete; lean static insurance remains hard to beat under surprise shocks, near the demand-capacity boundary, and wherever pre-shock slack makes insurance cheap. Attribution ablations separate certification maintenance, re-acquisition of lapsed certifications, and greenfield skill acquisition. Forecastability, not adaptivity per se, decides when predictive control pays.

18.
arXiv (CS.LG) 2026-06-16

Near-Optimal Regret for Distributed Adversarial Bandits: A Black-Box Approach

arXiv:2602.06404v2 Announce Type: replace Abstract: We study distributed adversarial bandits, where $N$ agents cooperate to minimize the global average loss while observing only their own local losses. We show that the minimax regret for this problem is $\tilde{\Theta}(\sqrt{(\rho^{-1/2}+K/N)T})$, where $T$ is the horizon, $K$ is the number of actions, and $\rho$ is the spectral gap of the communication matrix. Our algorithm, based on a novel black-box reduction to bandits with delayed feedback, requires agents to communicate only through gossip. It achieves an upper bound that significantly improves over the previous best bound $\tilde{O}(\rho^{-1/3}(KT)^{2/3})$ of Yi and Vojnovic (2023). We complement this result with a matching lower bound, showing that the problem's difficulty decomposes into a communication cost $\rho^{-1/4}\sqrt{T}$ and a bandit cost $\sqrt{KT/N}$. We further demonstrate the versatility of our approach by deriving first-order and best-of-both-worlds bounds in the distributed adversarial setting. Finally, we extend our framework to distributed linear bandits in $R^d$, obtaining a regret bound of $\tilde{O}(\sqrt{(\rho^{-1/2}+1/N)dT})$, achieved with only $O(d)$ communication cost per agent and per round via a volumetric spanner.

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

SoftMoE: Soft Differentiable Routing for Mixture-of-Experts in LLMs

arXiv:2606.17952v1 Announce Type: cross Abstract: Sparse Mixture-of-Experts (MoE) architectures enable scaling LLM parameters under a fixed inference budget by activating only a small subset of experts via top-$k$ routing. While this preserves causality and suits autoregressive language models, the discrete top-$k$ operator is not differentiable, forcing a fixed number of active experts per input and resulting in inefficient use of computation. We propose SoftMoE, which replaces discrete routing with a truncated soft top-$k$ LapSum relaxation, allowing gradient-based optimization of expert routing. We further parameterize the mean number of active experts per layer and impose a global budget constraint, enabling the model to learn how to allocate expert capacity across layers. SoftMoE remains fully compatible with autoregressive modeling and achieves performance comparable to or better than sparse MoE on language modeling and downstream tasks, while activating significantly fewer experts. Notably, the learned allocation is highly non-uniform, with later layers activating more experts. The source code is publicly available$^\dagger$.

20.
arXiv (quant-ph) 2026-06-17

Acceleration-induced spectral blind spots in stimulated atomic transitions

arXiv:2606.17396v1 Announce Type: cross Abstract: Stimulated transitions are among the most fundamental processes in light-matter interaction, underlying resonant absorption and emission in atomic systems. Here we show that uniform acceleration can convert this familiar response into a frequency-selective absence of response. Specifically, when an incident photon has a nonzero momentum component transverse to the acceleration, the stimulated transition probability vanishes at a discrete set of frequencies fixed by the acceleration, the atomic transition frequency, and the photon propagation angle. At these spectral blind spots, both ordinary stimulated absorption and acceleration-induced excitation are simultaneously suppressed, rendering the atom effectively unresponsive to the incident radiation. The effect arises from the nontrivial response of accelerated atoms to quantum vacuum fluctuations and provides a distinctive signature of the Unruh effect through the absence, rather than the enhancement, of stimulated transitions. We further provide an order-of-magnitude estimate showing that an electron-based implementation with spin splitting in combined electric and magnetic fields could access the required parameter regime. These results reveal an unexplored form of acceleration-modified light-matter interaction and identify spectral blind spots as a new manifestation of the Unruh effect.

21.
arXiv (CS.CL) 2026-06-12

Self-Distillation Zero: Self-Revision Turns Binary Rewards into Dense Supervision

Current post-training methods in verifiable settings fall into two categories. Reinforcement learning (RLVR) relies on binary rewards, which are broadly applicable and powerful, but provide only sparse supervision during training. Distillation provides dense token-level supervision, typically obtained from an external teacher or using high-quality demonstrations. Collecting such supervision can be costly or unavailable. We propose Self-Distillation Zero (SD-Zero), a method that is substantially more training sample-efficient than RL and does not require an external teacher or high-quality demonstrations. SD-Zero trains a single model to play two roles: a Generator, which produces an initial response, and a Reviser, which conditions on that response and its binary reward to produce an improved response. We then perform on-policy self-distillation to distill the reviser into the generator, using the reviser's token distributions conditioned on the generator's response and its reward as supervision. In effect, SD-Zero trains the model to transform binary rewards into dense token-level self-supervision. On math and code reasoning benchmarks with Qwen3-4B-Instruct and Olmo-3-7B-Instruct, SD-Zero improves performance by at least 10% over the base models and outperforms strong baselines, including Rejection Fine-Tuning (RFT), GRPO, and Self-Distillation Fine-Tuning (SDFT), under the same question set and training sample budget. Extensive ablation studies show two novel characteristics of our proposed algorithm: (a) token-level self-localization, where the reviser can identify the key tokens that need to be revised in the generator's response based on reward, and (b) iterative self-evolution, where the improving ability to revise answers can be distilled back into generation performance with regular teacher synchronization. Code: https://github.com/princeton-pli/Self-Distillation-Zero.

22.
bioRxiv (Bioinfo) 2026-06-11

Combinatorial docking and molecular generation to navigate over 100-billion molecules for prospective ligand discovery

Commercially available make-on-demand libraries now exceed 100 billion compounds, requiring over 50 years to screen on 2,000 CPU cores using conventional docking. We present two complementary approaches to address this challenge. CombiDOCK, a combinatorial docking framework, enables exhaustive screening at the 100-billion scale within 40 days. MINT-Dock, a generative framework, accelerates navigation of this space by integrating CombiDOCK with Monte Carlo Tree Search. Benchmarked on 46 diverse targets, CombiDOCK matched full-molecule docking accuracy, and MINT-Dock achieved a 4,800-fold enrichment over random selection. Compared with prior billion-scale brute-force campaigns against {sigma}2, VMAT2, and VAChT, prospective CombiDOCK screens of the 100-billion-molecule library yielded higher hit rates and more potent ligands, while MINT-Dock achieved comparable outcomes across single- and multi-target objectives with >20-fold computational cost reductions. Docking-predicted poses of the best VAChT-binding compounds were confirmed by cryo-EM structures. These methods provide exhaustive and generative paths for navigating the trillion-molecule frontier of drug discovery.

23.
arXiv (quant-ph) 2026-06-12

Non-Hermitian skin effect induced by spatial noncommutativity

arXiv:2606.12961v1 Announce Type: new Abstract: In all known schemes for the non-Hermitian skin effect, the non-Hermitian ingredient that drives the skin localization, whether asymmetric hopping or gain and loss, is invariably introduced by hand as an independent model parameter along the skin direction. Here we show that when two spatial coordinates do not commute, the skin effect can break free of this paradigm: a gain-loss potential applied along one coordinate automatically generates non-reciprocity along the other through the coordinate noncommutativity, driving all eigenstates to pile up exponentially at a boundary. We term this phenomenon the noncommutative skin effect. The inverse skin length is proportional to the noncommutativity parameter and is given by an analytic formula, exact in the thermodynamic limit and verified by exact diagonalization of lattice models; the reflection symmetry of the imaginary potential furnishes an exact criterion for the presence or absence of the effect, valid rigorously for finite-size systems. For a sinusoidal imaginary potential, the skin direction of all eigenstates flips collectively at parameter points fixed purely by geometry. Because the flip point is independent of the potential strength, the reversal constitutes a zero-crossing measurement scheme intrinsically robust against systematic errors, from which the noncommutativity parameter can be extracted directly. The qualitative transition of the eigenstates from uniform to exponentially localized renders the effect a nonperturbative probe of spatial noncommutativity, and the Peierls-phase structure of its lattice model is in principle accessible to cold-atom synthetic dimensions, photonic resonators, and topolectrical circuits.

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

SPARK: Security Knowledge Priming and Representation-Guided Knowledge Activation for LLM-based Secure Code Generation

arXiv:2606.16244v1 Announce Type: cross Abstract: Large language models routinely generate code with exploitable security flaws. Prior literature attributes this limitation to a lack of security expertise, steering current defense mechanisms toward heavy fine-tuning or external knowledge retrieval, which introduces significant computational overhead and data bias through redundant code examples. Contrary to this view, we argue that pretraining corpora are already rich in security material. The bottleneck is activation: without an explicit and brief cue, statistical pressure toward common training-distribution patterns suppresses the model's safety-relevant representations. We present SPARK, an inference-time security harness that activates this latent knowledge without any retraining. The harness has two parts. Component~I retrieves a few of the relevant Common Weakness Enumeration (CWE) entries for each coding task and appends a short structured cue to the prompt; this alone is enough to surface the model's existing security representations. Component~II adds a precomputed token bias to the logits at every decoding step. We obtain the bias by projecting a safe-direction vector, the unit difference between the mean safe and mean unsafe last-layer hidden states, through the language model head. The bias is computed once offline; applying it costs a single vector addition per generated token. We evaluate SPARK on 9 open-source models across C++, Java, and Python, and compare with 7 baselines spanning fine-tuning and retrieval-augmented methods. SPARK matches or improves on the best baseline in every setting while preserving HumanEval utility. We further test Component~I in a black-box setting on 7 of today's strongest models, including Claude, DeepSeek, and GPT, demonstrating the bottleneck of insecure code generation and the improvements enabled by our method.

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

Looking Is Not Picking: An Attention-Segment Account of Tool-Selection Failures in LLM Agents

作者:

arXiv:2606.16364v1 Announce Type: new Abstract: LLM agents mis-call tools, and the natural guess is that the model failed to see the right tool in a crowded harness. We show the opposite through a lens concurrent work sets aside – the model's attention to labeled tool-definition segments. On real BFCL failures, by per-candidate attention argmax the model attends most to the correct tool 80% of the time (vs. 21% chance), and the gold is the under-attended segment on only 10%: it looks at the right tool and still picks wrong. This directly refutes the intuitive "crowded-harness / lost-in-the-middle" explanation: the failure is at the decision readout, not the harness, and we pin it there three ways. (1) Input vs. readout: repairing the prompt (reordering or duplicating the gold tool) recovers