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

Implicit Variational Rejection Sampling

arXiv:2606.14235v1 Announce Type: new Abstract: Variational Inference (VI) is a fundamental inference technique in Bayesian machine learning for approximating complex posterior distributions. Traditional VI often relies on the mean-field factorization, which can inadequately capture true posterior complexity. Recent advancements have leveraged neural networks to model implicit distributions, offering increased flexibility. However, the practical constraints of neural network architectures still produces inaccuracies. In this paper, we propose a method called Implicit Variational Rejection Sampling (IVRS), which integrates implicit distributions with rejection sampling to improve the posterior approximation. Our method uses neural networks to construct implicit proposal distributions, and rejection sampling with a discriminator network that estimates the density ratio between the implicit proposal and the true posterior for refining the approximation. Towards this end, we introduce the Implicit Resampling Evidence Lower Bound (IR-ELBO) as a metric to characterize the resampled distribution's quality and derive a tighter variational lower bound. Experimental results demonstrate that our method outperforms traditional variational inference techniques.

02.
arXiv (CS.AI) 2026-06-16

Parallel Test-Time Scaling with Multi-Sequence Verifiers

arXiv:2603.03417v2 Announce Type: replace-cross Abstract: Parallel test-time scaling, which generates multiple candidate solutions for a single problem, is a powerful technique for improving large language model performance. However, it is hindered by two key bottlenecks: accurately selecting the correct solution from the candidate pool, and the high inference latency from generating many full solutions. We argue that both challenges are fundamentally linked to verifier calibration, as a well-calibrated verifier improves answer selection and enables early-stopping strategies to reduce latency. However, existing non-generative verifiers are limited as they score each candidate in isolation, overlooking rich contextual information across the set of candidates. To address this, we introduce the Multi-Sequence Verifier (MSV), a lightweight verifier that predicts each candidate's correctness conditioned on the full sampled set. MSV achieves improved calibration, which directly enhances best-of-N selection performance and empowers a novel early-stopping framework. Across challenging mathematical reasoning benchmarks, MSV improves best-of-64 accuracy by up to 6\% relative to strong baselines, and in the early-stopping setting reaches the same accuracy as baselines with less than half the latency.

03.
arXiv (CS.AI) 2026-06-11

When Does Deep RL Beat Calibrated Baselines? A Benchmark Study on Adaptive Resource Control

arXiv:2605.26418v2 Announce Type: replace-cross Abstract: A properly calibrated rule-based autoscaler can beat every one of six mainstream deep reinforcement learning (DRL) algorithms on cost across every workload we test - so when, if ever, does DRL actually help? We study this in RLScale-Bench, a reproducible benchmark and evaluation protocol for DRL on adaptive resource control, where an agent allocates compute to a dynamic workload under cost and service-level constraints. We evaluate PPO, DQN, A2C, SAC, TD3, and DDPG under matched architectures, training budgets, and reward functions against a calibrated rule-based baseline across six workload patterns and five seeds (240 runs), instantiate the benchmark on Kubernetes Horizontal Pod Autoscaling, and probe distribution-shift generalization. Three findings challenge common assumptions: (i) the calibrated controller achieves the lowest cost on all six workloads, though it trails the best RL agents on bursty and flash traffic; (ii) discrete-action algorithms outperform continuous-action ones by one to two orders of magnitude in constraint violations due to action-space mismatch; and (iii) no single algorithm dominates across workloads, with rankings shifting by up to four positions. The bottleneck in RL-based resource control is not algorithm selection but baseline calibration, reward engineering, and realistic evaluation protocols.

04.
Nature (Science) 2026-06-17

Structure of the pre-initiation complex explains CMGE biogenesis

When cells enter S phase, bidirectional DNA replication is initiated through the kinase-regulated recruitment of three activators (Cdc45, GINS and Pol ε) to a duplex-DNA-loaded double hexamer of minichromosome maintenance (MCM) ATPases. Together, these proteins form two CMGE helicases that establish divergent replication forks as they become separated1. Here, to gain an understanding of CMGE biogenesis, we reconstituted the pre-initiation complex with purified yeast proteins. The cryo-electron-microscopy structure shows a set of firing factors caught in the act of assembling two symmetrical CMGEs. We show how stepwise complex formation reshapes MCM in preparation for DNA opening, and we explain how ATP promotes firing-factor ejection and CMGE maturation. We find that although Sld2 facilitates the recruitment of GINS to MCM, as expected, it also aids the efficient separation of the CMGE dimer, and is essential for the ejection of the lagging strand from MCM. These findings have direct implications for our understanding of the metazoan Sld2 orthologue, RECQL4, and point to a replication-fork establishment mechanism that is conserved across eukaryotes. Cryo-electron microscopy and biochemical reconstitution experiments in yeast provide insight into the assembly of the CMGE complex, a helicase that establishes bidirectional DNA replication in eukaryotic cells, and elucidate the role of the firing factor Sld2.

05.
arXiv (CS.AI) 2026-06-19

Exploring Feature Extraction Technique Parameters for Acoustic Gunshot Classification

arXiv:2606.19568v1 Announce Type: cross Abstract: Acoustic gunshot detection is a problem with applications across civilian public safety, military operations, and wildlife conservation, yet the field lacks a rigorous exploration of feature extraction techniques with a focus on generalization to realistic data. The mixed effectiveness of commercial gunshot detection and classification systems indicates an open problem that is not adequately addressed by the current literature. In this paper, we present a systematic investigation of common feature extraction techniques using a dataset of 23,000 gunshot recordings across 85 firearms and 21 calibers. We benchmark three feature extraction techniques with 12 total unique parameter sets using ResNet-18. Our results demonstrate that using the correct feature extraction technique can improve top-1 accuracy by up to 20%, and utilizing the correct parameters for a given feature extraction technique can improve that value by up to 4.7%.

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

Asymptotically Optimal Circuit Depth for Diagonal Unitary Synthesis and Compilation on Two-Dimensional Grids

arXiv:2606.17589v1 Announce Type: new Abstract: Diagonal unitaries are a fundamental but resource-intensive class of quantum operations, arising as the phase separators of QAOA and the time-evolution blocks of Hamiltonian simulation. Under all-to-all connectivity their optimal depth is established, but on nearest-neighbor hardware general-purpose compilers fall back on heuristic search, which yields no analyzable cost bound and becomes intractable at the very sizes where depth is the bottleneck. We address synthesis and compilation jointly. On the synthesis side, we develop a Gray-Path Framework (GPF) that realizes any $n$-qubit diagonal unitary in asymptotically optimal $R_z$ and CNOT depth $O(2^n/n)$ without ancillas. Our main result is that compiling GPF onto a two-dimensional nearest-neighbor grid preserves this optimality: routing adds depth $\Theta(2^n/n)$ and gate count $\Theta(2^n)$. Because GPF fixes its entire interaction structure in advance, routing reduces to scheduling a known sequence, with no heuristic search. We give the construction both with and without ancillas: the ancilla-free, cost-optimized layout is a two-row grid, and a $2k$-row layout introduces a space–time tradeoff that cuts depth by $1/k$ while remaining asymptotically optimal for the enlarged register; both are deterministic and analyzed in closed form. The same complexity is also attained on a linear nearest-neighbor chain, so the preservation is topology-independent, holding on any architecture that contains such a chain. All routing bounds are closed-form, giving the concrete resource estimates that heuristic compilers cannot provide at scale.

07.
arXiv (CS.CL) 2026-06-16

Long-Context Modeling via GSS-Transformer Hybrid Architecture with Learnable Mixing

Modeling long-range dependencies remains a central challenge in natural language processing. Transformer architectures achieve strong performance via self-attention but scale quadratically ($O(N^2)$) with sequence length, while State Space Models (SSMs) scale linearly ($O(N)$) but suffer from a selective recall bottleneck, struggling to retrieve precise information from compressed states. This creates a fundamental tradeoff between efficiency and perplexity. To tackle these challenges, we propose the Parallel Hybrid Architecture (PHA), which runs Gated State Spaces (GSS), Grouped Query Attention (GQA), and Feed-Forward Networks (FFNs) as independent parallel branches fused by a learnable mixing mechanism. Instead of forcing SSMs to approximate attention or serializing the two paradigms, PHA allows each branch to specialize: GSS captures global context, while attention performs selective retrieval, with FFN providing complementary processing. On WikiText-103, PHA achieves 16.51 PPL at 125M parameters, outperforming Hedgehog (16.70) and H3-125M (23.70). Scaling to 180M parameters yields 16.42 PPL, which gives comparable results with the pure attention baseline while delivering 24\% higher throughput and up to 40\% lower memory usage at long contexts. On OpenWebText, our 125M model achieves 19.72 PPL, outperforming standard Transformers (20.60) and GSS hybrid baselines (19.80). These results demonstrate that separating sequence modeling paradigms into parallel specialists enables Transformer-level perplexity with substantially improved efficiency for long-context language modeling.

08.
arXiv (CS.LG) 2026-06-11

LakeFM: Toward a Foundation Model for Aquatic Ecosystems Using Irregular Multivariate Multi-depth Time Series Data

arXiv:2606.11268v1 Announce Type: new Abstract: Understanding and forecasting lake dynamics is critical for monitoring water quality and ecosystem health across lakes and reservoirs. While machine learning methods have been recently applied to ecological time-series data, existing works assume regular sampling in time and depth, and struggle to generalize across lakes with heterogeneous variables, depths, and observation patterns. To address these limitations, we introduce \textsc{LakeFM}, a foundation model for aquatic systems, pre-trained on large-scale ecological datasets comprising both simulated and observed lakes. Through extensive empirical evaluation, we show that \textsc{LakeFM} learns meaningful representations spanning broader lake-level characteristics, and achieves competitive or often superior-forecasting performance compared to existing time-series foundation and non-foundation models, while producing physically plausible predictions consistent with real-world lake dynamics.

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

Learning Augmented Exact Exponential Algorithms

arXiv:2606.18807v1 Announce Type: cross Abstract: The field of learning-augmented algorithms has demonstrated that machine-learned predictions can bypass worst-case lower bounds across a wide range of problems. So far, however, the focus has been almost exclusively on polynomial-time algorithms, where predictions improve competitive ratios, approximation guarantees, or running times. In this paper, we raise the question of whether predictions can push the frontier of exact exponential-time algorithms for NP-hard problems. We answer this question affirmatively by proposing a general approach that augments an entire family of state-of-the-art exact algorithms for a variety of subset selection problems. We show that a noisy predictor that is only marginally better than random guessing suffices to provably reduce the search space, and that the resulting runtime speedup scales smoothly with the prediction quality. Importantly, our algorithms require only pairwise independence of predictions or, alternatively, do not require the knowledge of the predictor's accuracy - both strictly weaker and more realistic settings than typically assumed.

10.
arXiv (CS.CL) 2026-06-17

Conformal Path Reasoning: Trustworthy Knowledge Graph Question Answering via Path-Level Calibration

Knowledge Graph Question Answering (KGQA) offers grounded, interpretable reasoning, but existing methods often fail to provide reliable coverage guarantees over retrieved answers. While Conformal Prediction (CP) offers a principled framework for producing prediction sets with statistical guarantees, prior conformal KGQA methods suffer from two critical pitfalls: violated coverage guarantees due to invalid calibration, and weak score discriminability that yields excessively large prediction sets. We propose Conformal Path Reasoning (CPR), a novel trustworthy KGQA framework built on two key innovations. First, query-level conformal calibration over path-level scores preserves exchangeability to ensure valid coverage guarantees. Second, we introduce the Residual Conformal Value Network (RCVNet), a lightweight module trained via PUCT-guided exploration to learn discriminative path-level nonconformity scores. Extensive experiments show that CPR significantly improves the Empirical Coverage Rate by 45% while reducing prediction set size by 52% on average over conformal baselines across benchmark datasets, highlighting its effectiveness for reliable conformal reasoning over knowledge graphs.

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

TrustedARI: Towards Trust-Native Agentic Routing Infrastructure for Agentic AI

arXiv:2606.15822v1 Announce Type: new Abstract: AI agents increasingly access external models, tools, and services through Agentic Routing Infrastructure (ARI) to manage the overhead of heterogeneous interfaces and fragmented subscriptions. Yet, the architecture of ARI introduces fundamental trust risks: it obtains plaintext access to agent queries and service responses, while leaving agents unable to verify that their queries are routed to intended service providers or that requests and responses remain untampered. To address this problem, we present TrustedARI, the first trust-native agentic routing infrastructure for agentic AI. Architecturally, TrustedARI is built upon three core innovations: (i) an ARI-adapted three-party TLS handshake that enables the agent and ARI to jointly authenticate the service provider through role-specific distribution of TLS key materials; (ii) a privacy-preserving query-construction protocol that allows the agent and ARI to collaboratively construct well-formed queries without exposing their respective private inputs; and (iii) a verifiable billing protocol that supports fair usage-based settlement while preserving the integrity and confidentiality of service responses. We implemented and extensively evaluated a prototype of TrustedARI to validate its performance. Experiments confirm that TrustedARI is highly efficient: our ARI-adapted handshake protocol reduces communication overhead by 39.34% compared to the existing three-party TLS handshake. Furthermore, the privacy-preserving query-construction protocol imposes negligible overhead-averaging 0.19 seconds in computation time and 0.58 MB in communication costs-while the verifiable billing protocol speeds up proof generation by 28.20x. Crucially, TrustedARI is readily deployable without any modification to the service providers.

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

Characterizing Nash Equilibria in Zero-Sum Games: A Physics-Inspired, Parallelizable Approach with a Linear Number of Gradient Queries

arXiv:2507.11366v2 Announce Type: replace-cross Abstract: We study online optimization methods for zero-sum games, a fundamental problem in adversarial learning in machine learning, economics, and many other domains. Traditional methods approximate Nash equilibria (NE) using either regret-based methods (time-average convergence) or contraction-map-based methods (last-iterate convergence). We propose a new method based on Hamiltonian dynamics in physics and prove that it can characterize the set of NE in a finite (linear) number of iterations of alternating gradient descent in the unbounded setting, modulo degeneracy, a first in online optimization. Unlike standard methods for computing NE, our proposed approach can be parallelized and works with arbitrary learning rates, both firsts in algorithmic game theory. Experimentally, we support our results by showing our approach drastically outperforms standard methods.

13.
arXiv (quant-ph) 2026-06-11

TensorKit.jl: A Julia package for large-scale tensor computations, with a hint of category theory

arXiv:2508.10076v2 Announce Type: replace-cross Abstract: TensorKit$.$jl is a Julia-based software package for tensor computations, especially focusing on tensors with internal symmetries. This paper introduces the design philosophy, core functionalities, and distinctive features, including how to handle abelian, non-abelian, and anyonic symmetries through the ``TensorMap'' type. We highlight the software's flexibility, performance, and its capability to extend to new tensor types and symmetries, illustrating its practical applications through select case studies.

14.
arXiv (CS.CV) 2026-06-15

High-Fidelity Video Compression based on Invertible Neural Transform and Implicit Conditioning

Learning-based video compression has recently achieved competitive rate-distortion performance compared to conventional video codecs. However, most existing methods rely on non-invertible analysis-synthesis transforms, with reconstruction quality subject to both quantization and transform approximation errors. This limitation becomes particularly restrictive at higher quality points, where quantization errors are small and transform-induced distortion dominates. To address this, we propose InnVC, an Invertible neural network based Video Codec for wide-range and high-fidelity compression. The core idea is to preserve an invertible main transform path prior to quantization, while injecting content-adaptive context through a compact implicit conditioning field. This decouples strongly correlated video content from harder-to-model fine details, allowing different components to specialize in complementary reconstruction tasks for more efficient compression. To further improve compressibility, we introduce a scheduled masking strategy that progressively concentrates informative content into fewer latent channels for more effective entropy coding. Experiments on the UVG and MCL-JCV benchmarks show that InnVC achieves strong compression performance over a broad quality range, being particularly effective in the high-quality regime, yielding BD-rate reductions of 21.66% in PSNR and 46.06% in MS-SSIM relative to x265 on UVG. To the best of our knowledge, InnVC is the first neural video codec covers operating poins from low bitrate to high fidelity within a single architecture scale, spanning more than 20 dB in PSNR.

15.
arXiv (math.PR) 2026-06-16

A 0-1 Law for Multifractal Spectra via the HGDS Scale Derivative

arXiv:2606.15850v1 Announce Type: new Abstract: We prove that the multifractal spectrum D(h,omega) of a stochastic process is almost surely deterministic under a scale decorrelation condition on the HGDS scale derivative. The key difficulty is that the pointwise Hölder exponent lives in the germ sigma-algebra, where classical 0-1 laws do not reach. We get around this by working with the geometry accumulation integral G_Lambda, which is a genuine Lebesgue integral over scales and concentrates almost surely. The boundary case – log-correlated fields – is sharp: the variance summability condition fails exactly there.

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

Multiple cyclicity and Wavelet Decomposition with Channel Correlation for Long-term Time Series Forecasting

arXiv:2606.17996v1 Announce Type: cross Abstract: Cyclicity and trend are important components of time series data and many studies based on cyclicity and trend have achieved good results in long-term time series forecasting. However, we believe that current work neglects the influence of real-world inter-channel correlations in time series data which leads to suboptimal predictions. Furthermore, these models rely on complex designs to capture diverse information so that resulting in low computational efficiency. To address this challenge, we propose McWC, a long-term time series forecasting model that separately models the cyclicity, trend, and inter-channel correlations. Specifically, McWC first decouples cyclical information from data using a multi-layer cyclicity construction module. Then, it extracts inter-channel correlations using multi-layer perceptron. Next, it models and fuses the multi-layer high-frequency and low-frequency information from data using a multi-level wavelet decomposition module. Finally, it aggregates the results of different components to obtain the output. Simultaneously, we decouple intra-channel autocorrelations by calculating a loss function in the frequency domain. Experiments on six real-world datasets demonstrate that McWC achieves state-of-the-art performance, exhibiting excellent computational efficiency and historical information extraction capabilities.

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

MoReBench: Evaluating Procedural and Pluralistic Moral Reasoning in Language Models, More than Outcomes

As AI systems progress, we rely more on them to make decisions with us and for us. To ensure that such decisions are aligned with human values, it is imperative for us to understand not only what decisions they make but also how they come to those decisions. Reasoning language models, which provide both final responses and (partially transparent) intermediate thinking traces, present a timely opportunity to study AI procedural reasoning. Unlike math and code problems which often have objectively correct answers, moral dilemmas are an excellent testbed for process-focused evaluation because they allow for multiple defensible conclusions. To do so, we present MoReBench: 1,000 moral scenarios, each paired with a set of rubric criteria that experts consider essential to include (or avoid) when reasoning about the scenarios. MoReBench contains over 23 thousand criteria including identifying moral considerations, weighing trade-offs, and giving actionable recommendations to cover cases on AI advising humans moral decisions as well as making moral decisions autonomously. Separately, we curate MoReBench-Theory: 150 examples to test whether AI can reason under five major frameworks in normative ethics. Our results show that scaling laws and existing benchmarks on math, code, and scientific reasoning tasks fail to predict models' abilities to perform moral reasoning. Models also show partiality towards specific moral frameworks (e.g., Benthamite Act Utilitarianism and Kantian Deontology), which might be side effects of popular training paradigms. Together, these benchmarks advance process-focused reasoning evaluation towards safer and more transparent AI.

18.
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/.

19.
arXiv (quant-ph) 2026-06-11

Isotropic random walks and Brownian diffusion on complex projective space

arXiv:2606.11438v1 Announce Type: new Abstract: We show that isotropic random walks on the complex projective space provide a canonical and analytically tractable stochastic-geometric framework for the exploration of quantum-state space. The approach combines harmonic analysis on compact rank-one symmetric spaces with stochastic pure-state evolution and yields explicit analytical expressions for transition kernels, fidelity statistics, and geometric observables associated with the Fubini–Study metric. In particular, the framework provides a solvable reference model for isotropic depolarization and Haar equilibration, reproducing Haar-random fidelity statistics and the invariant measure on projective Hilbert space without specifying a microscopic Lindblad generator. In the short-time regime, the stochastic evolution converges to Brownian diffusion generated by the Fubini–Study Laplace–Beltrami operator, while the long-time limit exhibits concentration-of-measure behaviour characteristic of high-dimensional random quantum states. We further derive analytical and asymptotic results for the first-passage-time problem, including closed-form expressions in the Brownian limit for the mean first passage time and the long-time tail of the first-passage-time distribution. For high-fidelity target states, the mean first passage time exhibits a strong dimension-dependent divergence originating from the concentration properties of the Fubini–Study geometry.

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

MedicalAgentsBench for Complex Medical Reasoning: Comparing Internalized Reasoning Models versus Externalized Agent-based Frameworks

Complex medical reasoning requires integrating heterogeneous clinical evidence across multiple inference steps. Large language models (LLMs) now approach this through two routes: internalized reasoning and externalized agent scaffolding (frameworks that decompose problems collaboratively amongst multiple LLMs). To determine whether these routes are exclusive or complementary, we introduce MedicalAgentsBench, a filtered benchmark of 862 complex clinical questions drawn from the union of eight medical datasets via difficulty-aware curation and contamination screening. Evaluating three internalized reasoning models (DeepSeek-R1, o1-mini, and o3-mini), seven base models, and nine externalized agent-based methods, we find that internalized and externalized approaches each independently improve performance, and that their benefits compound: the highest accuracy is achieved by layering agent workflows onto an internalized reasoning model (i.e., o3-mini + MDAgents with 35.1%). Pareto analysis shows this combination dominates the cost-performance frontier; moreover, lightweight optimization on inexpensive models offers an entry point for resource-constrained settings. Our benchmark is at https://github.com/gersteinlab/MedicalAgentsBench.

21.
arXiv (CS.CL) 2026-06-16

A Unified Definition of Hallucination: It's The World Model, Stupid!

Despite numerous attempts at mitigation since the inception of language models, hallucinations remain a persistent problem even in today's frontier LLMs. Why is this? We review existing definitions of hallucination and fold them into a single, unified definition wherein prior definitions are subsumed. We argue that hallucination can be unified by defining it as simply inaccurate (internal) world modeling, in a form where it is observable to the user. For example, stating a fact which contradicts a knowledge base OR producing a summary which contradicts the source. By varying the reference world model and conflict policy, our framework unifies prior definitions. We argue that this unified view is useful because it forces evaluations to clarify their assumed reference "world", distinguishes true hallucinations from planning or reward errors, and provides a common language for comparison across benchmarks and discussion of mitigation strategies. Building on this definition, we also connect our framework to HalluWorld, a complementary benchmark that instantiates fully specified reference world models for stress-testing model hallucinations.

22.
arXiv (CS.LG) 2026-06-18

KEPLA: A Knowledge-Enhanced Deep Learning Framework for Accurate Protein-Ligand Binding Affinity Prediction

arXiv:2506.13196v5 Announce Type: replace Abstract: Accurate prediction of protein-ligand binding affinity is critical for drug discovery. While recent deep learning approaches have demonstrated promising results, they often rely solely on structural features of proteins and ligands, overlooking their valuable biochemical knowledge associated with binding affinity. To address this limitation, we propose KEPLA, a novel deep learning framework that explicitly integrates prior knowledge from Gene Ontology and ligand properties to enhance prediction performance. KEPLA takes protein sequences and ligand molecular graphs as input and optimizes two complementary objectives: (1) aligning global representations with knowledge graph relations to capture domain-specific biochemical insights, and (2) leveraging cross attention between local representations to construct fine-grained joint embeddings for prediction. Experiments on two benchmark datasets across both in-domain and cross-domain scenarios demonstrate that KEPLA consistently outperforms state-of-the-art baselines. Furthermore, interpretability analyses based on knowledge graph relations and cross attention maps provide valuable insights into the underlying predictive mechanisms.

23.
PLOS Medicine 2026-06-09

Molecular Tumor Boards clinical impact on patient care and structural features: A systematic review and meta-analysis

作者:

by Luigi Russo, Erika Giacobini, Nicolò Lentini, Tommaso Osti, Maud Kamal, Stefania Boccia, Roberta Pastorino Background Molecular Tumor Boards (MTBs) bring together multidisciplinary experts to translate genomic data into clinical decisions in oncology, however, their overall clinical impact remains unclear. The aim of this systematic review is to assess the clinical impact of MTB-recommended therapies on patients with cancer outcomes. Methods and findings In this systematic review and meta-analysis, we searched PubMed, Embase, Scopus, and CENTRAL up to July 2025. We included studies of any design, both single-arm studies and studies with a comparator group, that reported the clinical impact of MTBs in patients who received MTB-guided therapy. Meta-analyses were performed separately by study design, using hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS), relative risks (RRs) for objective response rate (ORR) and disease control rate (DCR), and pooled proportions for PFS ratio ≥1.3. All meta-analyses were conducted using random-effects models based on the inverse variance method. We evaluated the risk of bias using the RoB 2.0 for RCTs and ROBINS-I for non-randomized studies.From 6,846 records, 78 studies (9,195 patients; 4,569 treated per MTB recommendations) were included. MTB-guided therapies were associated with reduced risk of death (HR 0.87; 95% CI [0.76, 1.01]; p = 0.069; I2 = 0.0% in RCTs; 0.62 in retrospective studies) and disease progression (HR 0.73; 95% CI [0.64, 0.84]; p 

24.
arXiv (CS.AI) 2026-06-18

Surrogate Benchmarks for Model Merging Optimization

arXiv:2509.02555v2 Announce Type: replace-cross Abstract: Model merging techniques aim to integrate the abilities of multiple models into a single model. Most model merging techniques have hyperparameters, and their setting affects the performance of the merged model. Because several existing works show that tuning hyperparameters in model merging can enhance the merging outcome, developing hyperparameter optimization algorithms for model merging is a promising direction. However, its optimization process is computationally expensive, particularly in merging LLMs. In this work, we develop surrogate benchmarks for optimization of the merging hyperparameters to realize algorithm development and performance comparison at low cost. We define two search spaces and collect data samples to construct surrogate models to predict the performance of a merged model from a hyperparameter. We demonstrate that our benchmarks can predict the performance of merged models well and simulate optimization algorithm behaviors.

25.
arXiv (CS.LG) 2026-06-11

Phi-Actor-Critic: Steering General-Sum Games to Pareto-Efficient Correlated Equilibria

arXiv:2606.11284v1 Announce Type: cross Abstract: Real-world multi-agent systems, from traffic coordination to resource allocation, are often modeled as general-sum games where individual incentives conflict with collective welfare. In these settings, the central challenge is not merely finding an equilibrium, but selecting socially desirable outcomes among many suboptimal Nash equilibria. Standard deep multi-agent reinforcement learning (MARL) methods struggle with this problem, as value-decomposition approaches are constrained by monotonicity assumptions and policy-gradient methods often converge to stable but socially inefficient equilibria. To address this limitation, we propose $\Phi$-Actor-Critic ($\Phi$-AC), a framework that leverages swap regret minimization to steer learning toward high-welfare correlated equilibria (CE). To make counterfactual regret estimation tractable in deep MARL, $\Phi$-AC employs a centralized attention critic that predicts vector-valued regrets in a single forward pass, avoiding computationally expensive counterfactual simulations. We further introduce a Lagrangian-based equilibrium selection mechanism that optimizes social welfare while enforcing stability through regret constraints. Experiments on matrix games, Multi-Agent Particle Environments (MPE), and the Melting Pot Harvest scenario demonstrate that $\Phi$-AC learns efficient and stable coordination strategies across diverse mixed-motive settings while maintaining high collective return and competitive fairness.