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01.
arXiv (quant-ph) 2026-06-15

Trap-Quenched Matter-Wave Optics for Dual Species Lensing

arXiv:2606.14577v1 Announce Type: cross Abstract: Dual-species atom interferometry in space promises precise tests of the Universality of Free Fall (UFF), with a sensitivity that grows quadratically with the extended interrogation time accessible in weightlessness. These tests demand exquisite control over the expansion energies of both condensed sources as well as over their differential center-of-mass dynamics. We propose a trap-quenched collimation technique featuring in-trap excitations of collective modes compatible with state-of-the-art atom-chip setups. Using NASA's Cold Atom Laboratory aboard the International Space Station, we demonstrate it on a single-species $^{87}$Rb condensate. By controlling the center-of-mass release dynamics we observe free expansion times up to 700 ms and measure a two-dimensional expansion energy of $k_B \cdot 78\pm 9 \;\mathrm{pK}$ in the imaging plane. A detailed model of the magnetically-induced dynamics indicates that this corresponds to a two-dimensional expansion energy of about $k_B \cdot 15^{+12}_{-5}\; \mathrm{pK}$ along two of the condensate's eigenaxes. Finally, we theoretically study this trap-quenched collimation scheme for a $^{41}$K-$^{87}$Rb mixture, predicting a simultaneous collimation that meets the expansion energy requirements for a state-of-the-art UFF test at the $10^{-15}$ accuracy level.

02.
arXiv (CS.CV) 2026-06-12

Triangle Splatting SLAM

We present a dense RGB-D SLAM system using differentiable triangles as the 3D map representation. While 3D Gaussian Splatting has emerged as the leading method for novel-view synthesis, triangles remain the standard primitive for traditional rendering hardware, game engines, and downstream tasks requiring explicit geometry such as simulation, collision, and editing. Recent offline methods have demonstrated that an unstructured 'triangle soup' can be optimised into a photorealistic mesh via Delaunay triangulation across a set of posed images. Building upon this insight, we present the first dense SLAM system to employ Triangle Splatting to perform both tracking and mapping through online differentiable rendering of a triangle soup. The map can be converted into a connected mesh on-the-fly via restricted Delaunay triangulation, enabling new online capabilities such as mesh deformation and collision checking. On Replica and TUM-RGBD, our system outperforms baselines on 3D geometry, matches the camera-tracking accuracy, and enables online mesh-based scene editing.

03.
arXiv (CS.AI) 2026-06-19

Implicit Semantic-Aware Communication Based on Hypergraph Reasoning

arXiv:2606.20162v1 Announce Type: new Abstract: Semantic-aware communication has emerged as a transformative paradigm for next-generation communication systems, shifting the fundamental goal from transmitting bit-level symbols to reliably recovering and understanding the semantic meaning of information. Previous studies have demonstrated that representing the semantic content of source messages as graph-based structures can significantly improve communication efficiency and the accuracy of semantic inference at the receiver. However, existing solutions typically employ graphs that capture only pairwise relationships, thereby neglecting higher-order implicit correlations commonly observed in real-world scenarios, such as group interactions, multi-entity associations, and complex relational contexts. This limitation reduces semantic expressiveness and makes semantic inference susceptible to ambiguity and performance degradation, particularly under noisy or corrupted channel conditions. To address these issues, this paper proposes a novel hypergraph-based implicit semantic reasoning framework, HISR, which leverages hypergraphs to represent complex multi-entity relationships among semantic knowledge entities. In HISR, entities and their associated higher-order relations are mapped into dedicated semantic subspaces tailored to distinct relational contexts. This design not only disentangles diverse semantic interactions to mitigate the over-smoothing effects commonly found in traditional graph embedding methods but also enables robust semantic inference even when partial information loss occurs during transmission. Numerical results show that the proposed HISR achieves up to a 36.6% improvement in implicit semantic interpretation accuracy over the state-of-the-art benchmarks.

04.
arXiv (quant-ph) 2026-06-11

PHASE: Pauli Hierarchical Assembly on Subdivided Elements for Quantum-Compatible Operator Synthesis

arXiv:2606.11478v1 Announce Type: new Abstract: Efficiently decomposing finite element stiffness matrices into the Pauli basis is challenging due to the exponential growth of Pauli strings with problem size. A naive Pauli expansion requires $\Theta(8^{\lceil \log_2 N \rceil})$ operations, where $N$ denotes the number of degrees of freedom, rendering direct decomposition infeasible for large systems. Existing approaches exploit algebraic sparsity or operator structure but do not incorporate the geometric organization intrinsic to finite element discretizations, and consequently exhibit poor scaling for stiffness matrices. To address this problem, we introduce PHASE, a hierarchical, geometry-aware Pauli decomposition algorithm that leverages recursive mesh partitioning to organize element contributions across multiple spatial scales. PHASE employs a hybrid strategy that combines full- and reduced-space Tensorized Pauli Decomposition with Fast Walsh-Hadamard Transform-based aggregation to assemble global Pauli coefficients efficiently. We show that this approach yields a dimension-dependent reduction in the exponential scaling exponent of Pauli assembly asymptotic complexity relative to existing methods, reducing the cost from $2^{2{\lceil \log_2 N \rceil}}$ to $2^{\gamma_d{\lceil \log_2 N \rceil}}$ with $\gamma_d < 2$ under standard mesh regularity and balanced partition assumptions. These results substantially improve the feasibility of quantum-compatible operator synthesis for large-scale finite element models.

05.
bioRxiv (Bioinfo) 2026-06-10

Is level-1 blob reconstruction under the network multispecies coalescent easy?

Authors:

Hybridization is an important evolutionary process, commonly modeled by the network multispecies coalescent. Reconstructing evolutionary histories under this model is notoriously costly, even for level-1 networks where hybridization events are isolated from each other. The widely used methods that combine speed with statistical guarantees rely on quartet concordance factors computed for all subsets of four species, resulting in an o(n^4k) bottleneck that severely limits scalability to large numbers of species (n) and genes (k). Among quartet-based methods, NANUQ+ is notable because it decomposes the problem into two steps: first reconstructing a tree of blobs, which compresses each non-treelike part of the network, called a blob, into a single vertex, and second reconstructing the internal structure of each level-1 blob, specifically its circular order and hybrid vertex. Here, we investigate whether level-1 blob reconstruction is difficult once the tree of blobs is known. We present a fast and statistically consistent algorithm, called NetCS, based on two simple primitives: majority voting and merge sort, circumventing the bottleneck of computing all quartet concordance factors. In simulations, NetCS achieved comparable accuracy to NANUQ+ and was dramatically faster, enabling analyses of 200 taxa and 1000 genes in only a few minutes. Both methods attained near-perfect accuracy when given the true tree of blobs; however, their performance degraded in end-to-end pipelines due to errors in tree of blobs reconstruction. Strikingly, even methods that reconstruct level-1 networks directly struggled to accurately predict hybrid ancestry. Our results suggest that reconstructing level-1 blobs is unexpectedly easy once the tree of blobs is known, and that a major challenge for phylogenetic network inference lies in accurate tree of blobs reconstruction.

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

Deterministic Policy Gradient for Learning Equilibrium in Time-Inconsistent Control Problems

arXiv:2606.11798v1 Announce Type: cross Abstract: In this paper, we develop a continuous-time model-free reinforcement learning algorithm to learn deterministic equilibrium policies in general time-inconsistent control problems. Utilizing the extended Hamilton-Jacobi-Bellman system, we recast the original time-inconsistent problem into an equivalent two-stage problem. In the first stage, for given auxiliary functions, we employ the deterministic policy gradient approach to learn an optimal policy in an auxiliary time-consistent control problem. In the second stage, given the updated policy, we exploit the inner fixed point iterations and some martingale characterizations to learn the auxiliary functions. As a theoretical contribution, we provide some mild model assumptions and establish the convergence of inner fixed point iterations. By repeating this actor-critic style of iterations across two stages, our algorithm aims to learn the equilibrium under different sources of time-inconsistency in a unified manner. The superior effectiveness of the proposed algorithm are illustrated in two classical financial applications with time-inconsistency: mean-variance portfolio management and optimal tracking portfolio under non-exponential discounting.

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

RoVE: Rotary Value Embeddings Attention for Relative Position-dependent Value Pathways

arXiv:2606.11275v1 Announce Type: cross Abstract: Rotary Position Embeddings (RoPE) make attention scores position-relative but leave the value pathway position-blind: the message sent by a value token is the same regardless of its distance from the query. We propose RoVE, a parameter-free modification that makes values position-sensitive by rotating them simultaneously with keys, and show that it turns RoPE attention into attentive convolution. This new perspective unifies several independent formulations of the same operation across computer vision, robotics, and modern LLM architectures. Trained 124M and 354M GPT-2 models show consistent empirical gains over RoPE on few-shot in-context learning, out-of-distribution perplexity, and long-context retrieval, with the clearest improvements on tasks that require long-range aggregation.

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

Quantum Reservoir Computing for Short-Term Power Load Forecasting in Resource-Constrained Energy Systems

arXiv:2606.12806v1 Announce Type: cross Abstract: Short-term load forecasting is essential for reliable energy management, but practical deployment on edge devices requires models that remain accurate under limited memory, finite measurement budgets, and hardware noise. This work proposes a hardware-efficient Quantum Reservoir Computing (QRC) framework for energy load forecasting, where a fixed quantum reservoir transforms temporal input windows into high-dimensional features and only a classical Elastic Net readout is trained. To reduce deployment cost, the trained readout is compressed using post-training fixed-point quantization at bit widths from 8 to 2 bits. The framework is evaluated on the Tetouan and Spain energy load datasets under exact statevector simulation, 512-shot finite sampling, and realistic hardware-noise models from IBM FakeTorino and IBM FakeMarrakesh. Results show that 6-bit readout precision preserves full-precision forecasting performance while reducing readout memory by 81.2%. Below this point, degradation becomes dataset dependent, with Tetouan showing stronger sensitivity and Spain degrading more gradually. Hardware-noise validation further shows that the trained readout transfers to noisy reservoir states without retraining. These findings support quantized QRC as a resource-aware forecasting approach for near-term quantum time-series applications.

09.
arXiv (CS.CV) 2026-06-16

Rotational Symmetry based Object Pose Estimation from Point Clouds in the Absence of Known 3D Models

Object pose estimation is crucial to many industrial applications, with one example being automated spray painting using a robot. However, confidentiality concerns often limit access to high-quality 3D models, posing a significant challenge for point-cloud-based pose estimation. In such scenarios, rotational symmetry, a readily accessible characteristic of many industrial objects, can provide valuable prior information to facilitate pose estimation.In this paper, we propose a method that leverages the rotational symmetry commonly found in industrial objects to address the challenge caused by the absence of 3D models. The object pose is jointly estimated with point cloud refinement through an iterative optimization process. This optimization relies on a rotational symmetry constraint loss. To construct this loss, each 3D point is rotated according to the currently estimated pose, and multiple correspondences are identified using nearest-neighbor search by exploiting the rotational symmetry property. These correspondences are then used to compute the rotational symmetry constraint loss, which iteratively refines both the pose and the point cloud.By explicitly incorporating rotational symmetry into the optimization process, the proposed method achieves robust pose estimation and generalizes well across diverse object types. The proposed method is evaluated on a dataset specifically created for point clouds without known 3D models, consisting of four categories of synthetic objects and one real wheel hub collected from a production line. Experimental results demonstrate that the proposed method achieves performance comparable to methods that rely on known 3D models.

10.
arXiv (CS.CV) 2026-06-16

Cascaded Sparse Autoencoders Learn Multi-Level Visual Concepts in Multimodal LLMs

Multimodal Large Language Models (MLLMs) have demonstrated strong performance on vision-language tasks, yet their internal visual representations remain difficult to interpret. Sparse Autoencoders (SAEs) provide a scalable way to decompose dense model activations into sparse, interpretable features. However, existing SAE architectures primarily recover flat feature dictionaries and are less suited for explicit multi-level concept organization. In this paper, we introduce cascaded sparse autoencoders (CSAEs) for learning hierarchical visual concepts in MLLMs. Rather than nesting or stacking SAE sparse activation codes, CSAEs train a second-level SAE directly on the decoder weights of the first-level SAE, treating learned low-level feature directions as inputs for higher-level abstraction. This design enables CSAEs to learn "concepts of concepts" while avoiding drawbacks from the shared-prefix coupling of nesting, Matryoshka-style hierarchies and the bottlenecks of naively stacked SAEs. Experiments across Qwen3-VL, Gemma-3, and LLaVA on multiple visual datasets show that CSAEs improve interpretability in terms of hierarchical concept coherence over state-of-the-art SAE baselines. Results on concept steering further demonstrate that the learned concept groups support effective group-level interventions in MLLM outputs.

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

Exploring Academic Influence of Algorithms by Co-occurrence Network Based on Full-text of Academic Papers

Algorithms have become central to scientific research in the era of artificial intelligence (AI). Although algorithm mentions in papers are often used to indicate popularity and influence, existing studies usually evaluate individual algorithms in isolation and pay limited attention to the collective influence formed through their interconnections. This study constructs large-scale algorithm co-occurrence networks in natural language processing (NLP) based on the full text of academic papers and investigates algorithm influence from a network perspective. Using deep learning models, we extract algorithm entities and build overall, cumulative, and annual co-occurrence networks. We analyze their structural characteristics and apply multiple centrality measures to assess the group influence of algorithms across the whole field and over time. The results show that algorithm networks display typical features of complex networks, with increasingly dense connections developing over approximately two decades. Classic, high-performing algorithms and those located at the intersections of different research periods tend to have high popularity, control, centrality, and balanced influence. When the influence of an algorithm declines, it usually loses its core network position first, followed by weaker associations with other algorithms. This study is the first large-scale analysis of algorithm co-occurrence networks. Covering more than four decades of academic publications, it provides a temporal and structural view of algorithm influence and offers a foundation for future research on networks linking algorithms, scholars, and tasks.

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

Kubo-Martin-Schwinger conditions for non-Hermitian systems

arXiv:2606.13251v1 Announce Type: new Abstract: We investigate the extension of the Kubo–Martin–Schwinger (KMS) thermal equilibrium condition to non-Hermitian Hamiltonians with real spectra and biorthogonal eigensystems, providing a systematic analysis through three complementary routes. Our central result is a thermodynamic characterisation of quasi-Hermiticity: for $H \in M_d(\mathbb{C})$ diagonalisable with real spectrum, the biorthogonal Gibbs functional $\omega_{\rm{bi}}(A) = Z_{\rm{bi}}^{-1} \sum_n e^{-\beta E_n}\langle\phi_n|A|\psi_n\rangle$ satisfies $\omega_{\rm{bi}}(A^\dag A) \geq 0$ for all $A$ if and only if $H$ is quasi-Hermitian. The proof constructs the metric $\eta$ directly from the eigenprojectors of $\omega_{\rm{bi}}$ via the Riesz representation theorem, with no prior choice of $\eta$, providing a metric-free certificate of quasi-Hermiticity outside the Mostafazadeh–Scholtz framework. Under the full quasi-Hermitian hypothesis, we prove that the $\eta$-Gibbs state $\omega_\eta(A) = Z_\eta^{-1}\, \rm{Tr}[\eta e^{-\beta H}A]$ satisfies all three analytic KMS conditions, using the Hadamard three-line theorem and Bari's theorem on Riesz bases. The result is non-trivial: the transported state $\hat\omega(X) = \rm{Tr}[e^{-\beta h}X\eta]/Z_\eta$ differs from the Gibbs state of the isospectral Hermitian partner $h = \eta^{1/2}H\eta^{-1/2}$ whenever $[\eta,h]\neq 0$, so the KMS property cannot be deduced from the Hermitian theory by similarity. The gap between this result and the full Haag–Hugenholtz–Winnink $C^*$-algebraic framework is identified. Failure modes at exceptional points and for complex spectra are analysed, and the relation to the Fagnola–Umanità quantum detailed balance condition for open systems is discussed.

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

DEEPRUBRIC: Evidence-Tree Rubric Supervision for Efficient Reinforcement Learning of Deep Research Agents

Deep research agents synthesize long-form reports by searching and reasoning over retrieved evidence. Reinforcement learning with rubric-based rewards improves these agents by optimizing them against checkable criteria that translate report quality into reward signals, but its efficiency depends on whether those criteria reliably capture the task scope and evidence needs. Most existing studies ask an LLM to generate rubrics for a given query, but when the model fails to infer the underlying information needs, the generated rubrics may be incomplete and reduce RL efficiency. To obtain more reliable query–rubric supervision, we introduce DeepRubric, a data construction framework that reverses this process: instead of inferring evaluation criteria for a given query, it first determines what an evidence-backed report should be evaluated on and then synthesizes aligned query–rubric pairs from those evaluation targets. Starting from a sampled seed topic, DeepRubric builds an evidence tree by recursively expanding evidence-backed sub-questions, whose leaves serve as atomic and verifiable evaluation targets. It then uses the evidence tree to synthesize the training query and rubrics, ensuring that the reward evaluates exactly the information requested by the query. Using DeepRubric, we construct 9K query–rubric supervision examples and train DeepRubric-8B with rubric-based GRPO, achieving comparable performance to prior open state-of-the-art deep research models across three benchmarks with roughly 13x fewer RL GPU-hours.

14.
arXiv (CS.LG) 2026-06-16

Repeated Bilateral Trade: The Quest for Fairness

arXiv:2606.15369v1 Announce Type: new Abstract: We study repeated bilateral trade from a fairness perspective. At each round, a fresh seller-buyer pair arrives, and the platform posts a price before observing the traders' valuations. Trade occurs only if both agents accept the price. Rather than maximizing only the gain from trade, we consider platforms that seek balanced divisions of the generated surplus. We show that natural fairness desiderata lead to a one-parameter Rawls-to-Nash family of fair-gain objectives, obtained by aggregating the seller's and buyer's net gains through nonpositive Hölder means. Unlike the standard gain-from-trade objective and the Rawlsian fair-gain objective studied in prior work, our proposed objectives induce a new statistical structure in which expected rewards are recovered from threshold feedback through a two-dimensional singular-kernel integral identity. This leads to a nonstandard pure-exploration problem whose natural estimators are rectangular double sums with row-column dependence and singular weights. Assuming independent i.i.d. seller and buyer valuation sequences with arbitrary unknown marginals, we characterize the optimal learning rates for the whole Rawls-to-Nash family of fair-gain objectives, giving matching fixed-confidence sample-complexity and regret bounds up to polylogarithmic factors.

16.
Nature (Science) 2026-06-24

Immunological mechanisms of mRNA vaccines for infectious diseases

Authors:

Nucleoside-modified mRNA–lipid-nanoparticle (mRNA–LNP) vaccines confer a high level of protection against severe COVID-19 and, since their first authorization for human use in 2020, have saved millions of lives. The efficacy of this vaccine platform relies on the induction of powerful and coordinated innate and adaptive immune responses. A deep understanding of the mechanisms of action by which mRNA–LNP vaccines drive protective immunity is crucial for advancing the development of next-generation mRNA vaccines with improved immunogenicity and tolerability. A flurry of recent studies has shed light on aspects of this vaccine modality’s modus operandi. Nonetheless, key gaps in knowledge remain, including understanding how LNPs are sensed by the immune system and exert their adjuvant activity, identifying the specific signals and cellular pathways critical for eliciting protective immune responses and determining whether it is feasible to uncouple vaccine immunogenicity and reactogenicity. Here we review the known and unknown features of the immunological mechanisms of mRNA–LNP vaccines for infectious diseases. Furthermore, we discuss how the components of this vaccine platform can be modified to fine-tune immune responses against challenging pathogens for which effective vaccines do not exist or need improvement. A Review of the immunological mechanisms of mRNA–lipid-nanoparticle vaccines for infectious diseases discusses how the components of this vaccine platform can be modified to fine-tune immune responses against challenging pathogens.

17.
bioRxiv (Bioinfo) 2026-06-11

ANCHOR: haplotype-aware allelic and isoform inference from single-cell long-read RNA sequencing with de novo variant calling

Long-read RNA sequencing enables haplotype- and isoform-resolved allelic analysis of transcriptomes, yet extending this capability to single cells and distinct cell types remains computationally challenging due to sparse coverage, sequencing errors, incomplete variant information, and reference-biased transcript assignment. Here we present ANCHOR, a haplotype-aware framework for single-cell long-read RNA sequencing that performs de novo expressed-variant discovery, molecule-level haplotype assignment and isoform-resolved allelic quantification. ANCHOR combines a signed-graph variant caller, pair hidden Markov modelling and beta-binomial UMI aggregation to infer parental allele counts for genes and splice-resolved isoforms, without requiring a pre-existing phased genotype or deep learning. In human single-cell long-read RNA benchmarks, ANCHOR improved variant-calling performance over tested long-read RNA callers at single-cell and low-to-moderate coverage, and its beta-binomial model reduced depth-driven false positives in allele-specific expression testing. Applied to newly generated single-cell long-read RNA-seq data from reciprocal mouse crosses during gastrulation, ANCHOR resolved cell-type- and isoform-specific parent-of-origin imprinting and identified an antagonistic maternally biased Sgce isoform. ANCHOR provides a general framework for allele- and isoform-resolved analysis of diploid single-cell long-read transcriptomes.

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

Trust Without Trusting: A Recomputable Trust Protocol for Autonomous Agents

arXiv:2605.06738v2 Announce Type: replace-cross Abstract: Autonomous AI agents already transact at production scale – 69,000 bots, 165 million transactions, $50 million in volume on a single marketplace – and any party can verify a signed credential without a central service. In an open agent world that covers most of what trust requires: there are no universal borders, and each party chooses for itself whom to deal with. Borders appear only where a closed space draws one – a marketplace, a platform, or a consortium sets house rules. Whoever draws the border holds the authority to apply it, and may apply it as they choose, behind closed doors. This paper addresses the gap that opens there: when you rely on someone else's border, how do you check that they applied their own published rules – taking no one's word for it, and handing the check to no new trusted party? Our answer is the Combined Evidence Protocol (CEP): a five-condition predicate any party recomputes from anchored data, turning "did the boundary-owner follow its own admission rules" into a fact anyone verifies rather than a claim anyone believes. The move that secures optimistic rollups secures this – correctness rests on recomputation, so the measurement belongs to everyone and the oracle problem dissolves. Its load-bearing setting is a consortium of co-equal, mutually distrusting peers under a shared charter, each able to verify, independently, that the rules they jointly agreed are the rules being applied. CEP belongs to the family of trustless systems – optimistic and zero-knowledge rollups, verifiable ML, self-sovereign-identity predicates. The infrastructure beneath it is live: a W3C VC + DID trust layer running since March 2026, anchored on Base L2, continuing arXiv:2605.06738 and standing on its own.

19.
arXiv (math.PR) 2026-06-18

Functional central limit theorems for non-local branching Markov processes

arXiv:2502.19382v2 Announce Type: replace Abstract: The aim of this paper is to study the fluctuations of a general class of supercritical branching Markov processes with non-local branching mechanisms. We establish functional central limit theorems and show that the limiting behaviour falls into three regimes, determined by the size of the spectral gap associated with the first-moment semigroup of the branching process. The main novelty is to develop a unified functional fluctuation theory for spatial branching Markov processes with non-local reproduction, allowing a general finite-dimensional spectral structure for the first-moment semigroup, including non-simple leading eigenvalues and nilpotent Jordan-type components. In doing so, we extend the classical small, critical and large fluctuation trichotomy beyond the finite-type and local spatial settings, and obtain limiting processes that capture the covariance structure induced by non-local offspring displacement.

20.
arXiv (CS.CL) 2026-06-15

X-OPD: Cross-Modal On-Policy Distillation for Capability Alignment in Speech LLMs

While the shift from cascaded dialogue systems to end-to-end (E2E) speech Large Language Models (LLMs) improves latency and paralinguistic modeling, E2E models often exhibit a significant performance degradation compared to their text-based counterparts. The standard Supervised Fine-Tuning (SFT) and Reinforcement Learning (RL) training methods fail to close this gap. To address this, we propose X-OPD, a novel Cross-Modal On-Policy Distillation framework designed to systematically align the capabilities of Speech LLMs to their text-based counterparts. X-OPD enables the Speech LLM to explore its own distribution via on-policy rollouts, where a text-based teacher model evaluates these trajectories and provides token-level feedback, effectively distilling teacher's capabilities into student's multi-modal representations. Extensive experiments across multiple benchmarks demonstrate that X-OPD significantly narrows the gap in complex tasks while preserving the model's inherent capabilities.

21.
bioRxiv (Bioinfo) 2026-06-11

A Deep Hypergraph Learning Model for Predicting Antimicrobial Combination Effects Across Bacterial Targets

Antimicrobial resistance (AMR) creates an urgent need for efficient strategies to identify effective antibacterial combinations. Combination therapy, including antimicrobial peptides (AMPs) paired with conventional antibiotics, is a promising approach, but exhaustive experimental screening across drug pairs and bacterial targets is impractical. This study introduces a hybrid GCN-based hypergraph neural network (HGNN) for predicting antimicrobial-agent combination outcomes against bacterial targets. Each antimicrobial-agent-antimicrobial-agent-bacterium triplet is represented as a ternary hyperedge, enabling the model to learn context-dependent interaction patterns. The framework integrates SMILES-derived molecular graph embeddings for antimicrobial agents, including conventional antibiotics and AMPs, with taxonomy-derived bacterial representations. The prediction task was formulated as a three-class classification problem: synergy, antagonism, and non-interaction. The non-interaction class included experimentally verified indifferent records and synthetic presumed non-interaction triplets generated by negative sampling. Model development used drug-pair-grouped splitting, five-fold grouped cross-validation within the training/validation partition, and final evaluation on a held-out test set. On the held-out three-class test set, the selected GCN-based HGNN achieved an accuracy of 0.83, weighted F1-score of 0.84, macro F1-score of 0.80, and ROC-AUC of 0.95. Per-class evaluation showed accuracies of 0.80 for synergy, 0.92 for antagonism, and 0.85 for non-interaction. Pair-type analysis showed strong performance across AMP-AMP, AMP-conventional antibiotic, and conventional antibiotic-conventional antibiotic combinations. These findings suggest that hypergraph-based representation learning can support computational prioritization of antimicrobial combinations for experimental follow-up. Further studies will be needed to improve model interpretability and to perform prospective validation of predicted synergistic combinations.

22.
medRxiv (Medicine) 2026-06-24

Deleterious mitochondrial heteroplasmy drives high-risk clonal hematopoiesis and hematological malignancy

Abstract Mitochondrial DNA (mtDNA) heteroplasmy, the coexistence of multiple mtDNA variants within cells, accumulates with age and is associated with hematological malignancies and mortality. However, whether predicted deleterious heteroplasmies causally contribute to cancer or merely represent passenger mutations remains unresolved. Here, leveraging ~36,000 first-degree relative pairs from the UK Biobank and All of Us Research Program cohorts, we deconvolute overall heteroplasmy metrics into those that are shared across family members (representing inherited variants) and those that are not (representing de novo variants) to establish a Mendelian randomization framework for assessing causality. We show that shared heteroplasmies exhibit strong purifying selection, with reduced predicted deleteriousness compared to not shared variants, and that 90% of an individual's deleterious heteroplasmy burden is somatically acquired. Critically, shared deleterious heteroplasmy burden, fixed at conception and thus temporally upstream of potential confounders, is significantly associated with hematological malignancies (RR=2.81, 95% CI 1.29-6.13), with effect sizes concordant with the not shared heteroplasmy burden. Furthermore, shared deleterious heteroplasmy specifically associates with high-risk clonal hematopoiesis of indeterminate potential (CHIP), particularly spliceosome mutations, suggesting mitochondrial dysfunction promotes clonal expansion of specific CHIP subtypes. Finally, we identify ultra-rare individual mtDNA variants associated with hematological malignancies, a hallmark of driver mutations. These findings establish mtDNA heteroplasmies, including inherited variants, as causal contributors to hematological malignancy risk and demonstrate that most disease-relevant burden is acquired during life, identifying potential opportunities for prevention and therapeutic intervention in individuals at elevated risk for hematological cancer, particularly of myeloid origin.

23.
arXiv (CS.CV) 2026-06-19

Hierarchical mutual distillation for multi-view fusion: Learning from all possible view combinations

Multi-view learning often struggles to effectively leverage images captured from diverse angles and locations. Learning methods for unstructured multi-view images remain largely underexplored. We propose a novel Hierarchical Mutual Distillation for Multi-View Fusion (HMDMV) method, which can handle both structured and unstructured multi-view scenarios. It makes predictions utilizing all possible view combinations: single view, partial multi-view, and full multi-view. The method generates predictions for each view combination and then applies hierarchical mutual distillation to enhance inter-view consistency. An uncertainty-based weighting mechanism further refines the fusion process by adjusting the influence of each view combination according to its prediction confidence, reducing the impact of low-confidence views. Extensive experiments on large-scale structured and unstructured datasets demonstrate that HMDMV consistently achieves state-of-the-art classification accuracy. Another unique advantage of HMDMV is that it provides improved flexibility in inference, allowing for more or fewer view counts in inference than those used in training without additional processing. We also provide a light version with reduced training cost by designing an efficient strategy that randomly samples subsets of view combinations during each training iteration. These results highlight HMDMV's robustness in real-world settings where view availability is variable or incomplete. The code is available at https://github.com/labhai/HMDMV.

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

Hessian-augmented Supervised Learning for Hamilton-Jacobi-Bellman PDEs

arXiv:2606.23827v1 Announce Type: cross Abstract: A data-driven method is developed for approximating value functions in deterministic optimal control problems with nonlinear control-affine dynamics. The Pontryagin Maximum Principle optimality system is solved from multiple initial conditions to generate training data consisting of values, gradients, and Hessians of the value function, where Hessian information is obtained from a matrix Riccati equation along optimal trajectories. These quantities augment a weighted least-squares regression over sparse polynomial bases on hyperbolic cross index sets, with gradients and Hessians contributing additional linear equations per sample and substantially reducing sample complexity compared to value-only regression. Feedback laws are recovered analytically from the learned value function. In high dimensions, a partial Hessian strategy controls the cost of data generation. The approach is validated on problems of increasing state dimension, where second-order data augmentation is shown to improve approximation accuracy and closed-loop performance, with up to an order-of-magnitude reduction in the number of training samples required relative to lower-order methods.

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

Right Regions, Wrong Labels: Semantic Label Flips in Segmentation under Correlation Shift

The robustness of machine learning models can be compromised by spurious correlations between non-causal features in the input data and target labels. A common way to test for such correlations is to train on data where the label is strongly tied to some non-causal cue, then evaluate on examples where that tie no longer holds. This idea is well established for classification tasks, but for semantic segmentation the specific failure modes are not well understood. We show that a model may achieve reasonable overlap while assigning the wrong semantic label, swapping one plausible foreground class for another, even when object boundaries are largely correct. We focus on this semantic label-flip behaviour and quantify it with a simple diagnostic (Flip) that counts how often ground truth foreground pixels are assigned the wrong foreground identity while remaining predicted as foreground. In a setting where category and scene are correlated during training, increasing the correlation consistently widens the gap between common and rare test conditions and increases these within-object label swaps on counterfactual groups. Overall, our results motivate assessing segmentation robustness under distribution shift beyond overlap by decomposing foreground errors into correct pixels, flipped-identity pixels, and missed-to-background pixels. We also propose an entropy-based, ground truth label-free `flip-risk' score, which is computed from foreground identity uncertainty, and show that it can flag flip-prone cases at inference time. Code is available at https://github.com/acharaakshit/label-flips.