Academic Intelligence · Curated Daily

探索全球前沿学术脉络

AcademicHub 汇聚顶级期刊与预印本平台的实时文献。定制您的专属科研雷达,利用大语言模型自动生成交叉领域文献分析简报。

01.
arXiv (CS.CL) 2026-06-18

FLiP: Towards understanding and interpreting multimodal multilingual sentence embeddings

This paper presents factorized linear projection (FLiP) models for understanding pretrained sentence embedding spaces. We train FLiP models to recover the lexical content from multilingual (LaBSE), multimodal (SONAR) and API-based (Gemini) sentence embedding spaces in several high- and mid-resource languages. We show that FLiP can recall more than 75% of lexical content from the embeddings, significantly outperforming existing non-factorized baselines. Using this as a diagnostic tool, we uncover the modality and language biases across the selected sentence encoders and provide practitioners with intrinsic insights about the encoders without relying on conventional downstream evaluation tasks. Our implementation is public https://github.com/BUTSpeechFIT/FLiP.

02.
medRxiv (Medicine) 2026-06-17

Short-term relaxation after cervical rotatory manipulation is more closely associated with somatosensory input than cracking sound: a randomized controlled EEG study

Background Cervical rotatory manipulation is commonly used for neck-related symptoms and is often accompanied by a cracking sound. This sound is frequently regarded as a sign of successful manipulation, but whether it contributes substantially to the immediate relaxation response remains unclear. Objective This study examined whether short-term relaxation after cervical rotatory manipulation is more closely related to manipulation-associated sensory input than to the cracking sound cue alone. Methods In this single-session, three-arm, parallel randomized controlled study, 54 healthy volunteers were allocated to cervical rotatory manipulation, sham manipulation, or sham manipulation plus simulated cracking sound. Subjective outcomes were assessed before and after intervention, including positive affect, negative affect, comfort, and satisfaction. Eyes-closed resting-state electroencephalography was recorded before and after intervention. Prespecified neural outcomes included frontal alpha power, frontal alpha/beta ratio, occipital individual alpha frequency, and alpha-band fronto-parietal and fronto-temporal functional connectivity. Results Cervical rotatory manipulation produced greater improvements in positive affect, comfort, and satisfaction than sham manipulation or sham manipulation plus simulated cracking sound, whereas negative affect remained generally stable across groups. These subjective responses were accompanied by short-term electroencephalography changes, particularly in frontal alpha/beta and alpha-band fronto-parietal and fronto-temporal functional connectivity. Changes in frontal alpha/beta ratio were positively associated with changes in positive affect. In contrast, simulated cracking sound alone did not reproduce the full subjective or electroencephalography response observed after real manipulation. Conclusions The immediate relaxation response after cervical rotatory manipulation appears to be more closely related to manipulation-associated sensory input than to the cracking sound cue alone. These findings provide preliminary neurophysiological evidence for distinguishing real manipulation effects from sound-related contextual cues.

03.
bioRxiv (Bioinfo) 2026-06-16

FlowBench: separating planning, fault recovery and interpretation in agentic bioinformatics

Agentic large language model (LLM) systems are being deployed in bioinformatics faster than they are understood, and single-metric evaluations conflate capabilities that fail independently. We introduce FlowBench, a benchmark that decomposes agentic bioinformatics performance into planning, fault recovery, biological interpretation, and end-to-end output-fidelity. Existing systems achieve high plan completeness, but their closed, single-provider designs prevent attribution of performance to scaffolding versus the underlying model. We therefore built FlowAgent, a modular, provider-agnostic framework whose components can be selectively disabled and whose backbone model can be swapped across providers on a shared harness, and used it to evaluate 23 models from three main providers. Three findings emerge. First, generating a valid workflow plan from a named toolchain is largely solved, whereas inferring an appropriate toolchain from biological intent alone is uniformly difficult regardless of model tier, compressing all models into a narrow 44-57% pass-rate band. Second, ablation shows that the dependency-structured plan and a completeness-reflection step drive performance, while adding a same-context validator-driven retry makes structural quality worse. Third, fault recovery and data-grounded interpretation remain unsolved. Models frequently propose fixes that force a clean exit while leaving the underlying data invalid, and data-grounded interpretation lags internal-knowledge recall by a consistent margin. Safety does not emerge from capability, and reasoning-tier models were among the least reliable at recognising unrecoverable faults. Once planning saturates, agent architecture and refusal calibration, not model scale, are the productive frontier.

04.
arXiv (quant-ph) 2026-06-17

Coherent Control of an Embedded Bound State Without a Spectral Gap

作者:

arXiv:2606.17685v1 Announce Type: new Abstract: Bound states in the continuum (BICs) can confine photonic excitations in open systems without conventional cavities or band gaps, making them natural candidates for long-lived quantum storage and single-photon control. Their use is limited, however, by two obstacles: they are dark to incident photons, and they lack spectral-gap protection from the surrounding continuum. We overcome both limitations in a giant atom coupled to a one-dimensional waveguide using two temporal control knobs. Atomic-frequency modulation breaks and restores the destructive-interference condition, enabling deterministic capture and release of mode-matched single photons. Coupling modulation instead preserves the BIC condition while tuning the atomic and photonic weights of the stored state. A key result is that this embedded state can nevertheless be controlled adiabatically despite the absence of a spectral gap, with an intrinsic leakage probability linear in the ramp rate. By separating radiative access from BIC-preserving deformation, the protocol turns a dark BIC into a single-photon memory whose fidelity is set by the intrinsic continuum-induced leakage law, providing a route to embedded-state control in open photonic platforms.

05.
arXiv (CS.LG) 2026-06-16

Stochastic trace estimation with tensor train random vectors

arXiv:2606.15679v1 Announce Type: cross Abstract: Stochastic trace estimation is a standard tool for approximating the trace of a large-scale matrix available only through matrix-vector products. However, in tensor-structured settings, unstructured Gaussian or Rademacher test vectors may be prohibitively expensive to store and compute with, while cheaper rank-one tensor-product vectors can require sample complexities that grow exponentially with the tensor order. This work studies Gaussian random tensor train vectors as a structured alternative for stochastic trace estimation. We show that, with a suitable choice of the tensor train rank, random tensor train vectors recover dimension-independent guarantees for the Girard–Hutchinson estimator. In particular, a median-of-means variant with tensor train rank $r \geq d-1$ achieves the same dependence on the accuracy $\varepsilon$ and failure probability $\delta$ as the classical estimator based on unstructured Gaussian vectors. We further prove an oblivious subspace injection result for sketches formed from independent Gaussian random tensor train vectors: tensor train rank $r\geq d-1$ and $\mathcal{O}(\varepsilon^{-2}(k+\log(1/\delta)))$ samples suffice for a $k$-dimensional target subspace. Finally, we investigate the use of such sketches within the Nystr\"{o}m++ framework. We show that the resulting estimator can achieve the desired $\mathcal{O}(\varepsilon^{-1})$ sample complexity under an additional spectral-tail condition. These results provide clarififcation on both the potential and the limitations of random tensor train vectors in stochastic trace estimation.

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

VoidPadding: Let [VOID] Handle Padding in Masked Diffusion Language Models so that [EOS] Can Focus on Semantic Termination

MDLMs generate text by denoising a preallocated masked response canvas, making response-length modeling central to instruction tuning. Existing MDLMs often inherit the autoregressive convention of using repeated \texttt{[EOS]} tokens for padding during instruction tuning, giving \texttt{[EOS]} a dual role as both a semantic terminator and a padding token. We show that this dual role is a root cause of \texttt{[EOS]} overflow under large-block decoding. To decouple these roles, we propose VoidPadding, which introduces \texttt{[VOID]} for padding and reserves \texttt{[EOS]} for termination. During inference, the learned \texttt{[EOS]} signal enables early stopping, while the learned \texttt{[VOID]} signal guides adaptive response canvas expansion. On Dream-7B-Instruct, VoidPadding improves the block-size-averaged four-task mean across mathematical reasoning and code generation benchmarks by \(+17.84\) points over the original model and \(+6.95\) points over RainbowPadding, while reducing decoding NFE by 55.7\% on average. Code is available at https://github.com/Haru-LCY/VoidPadding.

07.
arXiv (CS.AI) 2026-06-12

TrajGenAgent: A Hierarchical LLM Agent for Human Mobility Trajectory Generation

arXiv:2606.12657v1 Announce Type: new Abstract: Human mobility data is important for transportation, urban planning, and epidemic control, but large-scale trajectory collection is often costly and privacy-constrained, motivating realistic synthetic trajectory generation. Existing LLM-based generators typically rely on either prompt engineering, which preserves zero-shot reasoning but lacks fine-grained spatiotemporal grounding, or trajectory-level fine-tuning, which improves statistical precision but incurs substantial computational cost and may weaken general reasoning. We propose TrajGenAgent, a semantic-aware hierarchical LLM-agent framework for human mobility trajectory generation without model fine-tuning. TrajGenAgent uses a two-stage orchestrator-worker design: an LLM first synthesizes an individual- and weekday-conditioned activity chain from historical evidence via in-context learning, and a deterministic workflow then grounds each activity into a complete visit using personalized POI retrieval, distance-aware location selection, kinematics-aware travel-time propagation, and LLM-based duration estimation. To evaluate realism beyond aggregate spatiotemporal statistics, we introduce an anomaly-detection-based evaluation framework using two complementary detectors to assess behavioral and semantic plausibility. Experiments on benchmark and large-scale simulation datasets show that TrajGenAgent improves spatiotemporal fidelity, semantic coherence, and individual-specific behavioral realism over representative neural and LLM-based baselines, while avoiding parameter updates.

08.
arXiv (CS.LG) 2026-06-19

PU-UNet: Stable Multiplicative Interactions for Medical Image Segmentation

arXiv:2606.20035v1 Announce Type: cross Abstract: Many dense prediction networks rely on additive feature transformations and model higher-order feature interactions only implicitly. Product units provide an explicit mechanism for multiplicative feature modeling, but their logarithmic–exponential formulation can cause numerical instability, which has limited their use in deep dense prediction networks. In this work, we propose Product-Unit U-Net (PU-UNet), a residual U-Net that integrates stable product-unit residual blocks into rich low-resolution stages for medical image segmentation. The proposed formulation combines smooth positivity mapping with log-domain clipping, enabling stable multiplicative feature learning with negligible computational overhead. On ISIC 2018, Kvasir-SEG, and BUSI, PU-UNet achieves Dice scores of 0.942, 0.959, and up to 0.925, respectively. Compared with a matched Residual U-Net baseline, PU-UNet consistently improves Dice and IoU while keeping parameters, FLOPs, and inference latency nearly unchanged, and reduces the image-level false-positive rate on normal BUSI cases from 0.077 to zero. Ablation studies suggest that the gains are associated with product-unit interactions, are strongest under low-resolution placement, and benefit from the proposed stabilization design. These results suggest that stable product-unit residual learning can be an effective way to enhance U-Net-style segmentation networks with explicit multiplicative interactions.

09.
arXiv (CS.CV) 2026-06-11

Temporal2Seq: A Unified Framework for Temporal Video Understanding Tasks

With the development of video understanding, there is a proliferation of tasks for clip-level temporal video analysis, including temporal action detection (TAD), temporal action segmentation (TAS), and generic event boundary detection (GEBD). While task-specific video understanding models have exhibited outstanding performance in each task, there remains a dearth of a unified framework capable of simultaneously addressing multiple tasks, which is a promising direction for the next generation of AI. To this end, in this paper, we propose a single unified framework, coined as Temporal2Seq, to formulate the output of these temporal video understanding tasks as a sequence of discrete tokens. With this unified token representation, Temporal2Seq can train a generalist model within a single architecture on different video understanding tasks. In the absence of multi-task learning (MTL) benchmarks, we compile a comprehensive co-training dataset by borrowing the datasets from TAD, TAS, and GEBD tasks. We evaluate our Temporal2Seq generalist model on the corresponding test sets of three tasks, demonstrating that Temporal2Seq can produce reasonable results on various tasks and achieve advantages compared with single-task training on this framework. We also investigate the generalization performance of our generalist model on new datasets from different tasks, which yields superior performance to the specific model.

10.
arXiv (CS.CL) 2026-06-19

DeFrame: Debiasing Large Language Models Against Framing Effects

As large language models (LLMs) are increasingly deployed in real-world applications, ensuring their fair responses across demographics has become crucial. Despite many efforts, an ongoing challenge is hidden bias: LLMs appear fair under standard evaluations, but can produce biased responses outside those evaluation settings. In this paper, we identify framing – differences in how semantically equivalent prompts are expressed (e.g., "A is better than B" vs. "B is worse than A") – as an underexplored contributor to this gap. We first introduce the concept of "framing disparity" to quantify the impact of framing on fairness evaluation. By augmenting fairness evaluation benchmarks with alternative framings, we find that (1) fairness scores vary significantly with framing and (2) existing debiasing methods improve overall (i.e., frame-averaged) fairness, but often fail to reduce framing-induced disparities. To address this, we propose a framing-aware debiasing method that encourages LLMs to be more consistent across framings. Experiments demonstrate that our approach reduces overall bias and improves robustness against framing disparities, enabling LLMs to produce fairer and more consistent responses.

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

Probabilistic Contrastive Pretraining for Multi-task ADME Property Prediction

arXiv:2606.11508v1 Announce Type: new Abstract: Accurate prediction of absorption, distribution, metabolism, and excretion (ADME) properties is critical to drug discovery, but remains challenging because ADME endpoints are noisy, interdependent, and often data-limited. We propose a molecular graph-transformer pretraining framework that combines chemistry-specific self-supervision with contrastive mutual information machine learning (cMIM). Our method encodes molecular graphs into latent variables, reconstructs SMILES strings from the graph-derived latent codes, and augments the contrastive objective with domain-specific self-supervised chemistry tasks. Rather than treating these tasks as auxiliary regularizers with separately tuned loss weights, we formulate reconstruction, contrastive discrimination, and chemistry-specific supervision as unit-weighted log-probability factors in a single probabilistic latent-variable objective. For fine-tuning, we propose a multi-task GNN readout architecture with task-specific multilayer perceptron heads, preserving shared representation learning while mitigating negative transfer and improving the modeling of heterogeneous, nonlinear task relationships. Across Biogen, ExpansionRX, and ChEMBL-MT, the resulting Contrastive KERMT pretraining improves over the KERMT baseline by 7.6%, 9.9%, and 9.5% respectively (averaged over significantly-improved endpoints). Adding ADME-adjacent molecules to the pretraining corpus further improves transfer, and the contrastive component sharpens chemically meaningful latent neighborhoods.

12.
arXiv (math.PR) 2026-06-16

Sharp freezing time estimates for the subcritical Facilitated Exclusion Process

arXiv:2606.15233v1 Announce Type: new Abstract: We investigate the exact transience time of the Facilitated Exclusion Process (FEP) on the one-dimensional torus with $N$ sites. The FEP exhibits an active/inactive phase transition at critical density $1/2$, such that in the subcritical density regime $(0,1/2)$, it becomes frozen after a finite time period – the transience time or freezing time. We first show that for the FEP starting from a Bernoulli product measure of marginal density $\rho \in (0,1/2)$, the transience time has exactly the scale of $\Theta(\log^3 N)$. Secondly, we prove that in the near-critical case $\rho \simeq 1/2 - N^{-\alpha}$ for $\alpha \in (0,1)$, the transience time is polynomial and has a scale of $N^{1 \wedge (2\alpha)}$. The key idea is to estimate the typical size of locally supercritical intervals of the initial distribution, which has order $\log N$ in the subcritical case and $N^{1 \wedge (2\alpha)}$ in the near-critical case. In the subcritical case this is enough, whereas in the near-critical case we need additional dynamical decorrelation inequalities to apply this static result to estimate the freezing time.

13.
PLOS Computational Biology 2026-06-11

Catecholamine precursor modulation of human exploration: Evidence from a large gender-balanced sample

by Angela Mariele Brands, Kilian Knauth, David Mathar, Tim Roedder, Kerstin Lisner, Jan Peters The catecholamine precursor Tyrosine has been linked to improved cognitive performance, but investigations into decision-making and reinforcement learning processes known to be under catecholamine control are sparse. We examined the impact of a single dose of Tyrosine (2g) on reinforcement learning and exploration in a large (n = 63) gender-balanced sample in a within-subjects preregistered study. Reinforcement learning performance was significantly improved under Tyrosine. Based on previous work, we preregistered the hypotheses that Tyrosine would reduce directed exploration, response times, and physiological arousal. However, neither response times nor physiological arousal revealed the predicted reductions. Computational modelling using an established pre-registered reinforcement learning model revealed that the performance improvement under Tyrosine was due to an increase value-driven exploitation, without affecting directed exploration. Non-preregistered modelling analyses then revealed that accounting for higher-order perseveration substantially improved model fit, and substantiated the observation of increased value-driven exploitation under Tyrosine. Furthermore, it revealed reliable reductions in directed exploration and value-independent perseveration under Tyrosine. Tyrosine thus improved reinforcement learning performance by stabilizing choice patterns in the service of optimizing reward accumulation, modulating several computational mechanisms thought to be under catecholamine control.

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

RankVR: Low-Rank Structure Perception and Value Recalibration for Robust Composed Image Retrieval

Composed Image Retrieval (CIR) constitutes a pivotal paradigm requiring models to perform joint reasoning on reference images and modification texts. However, the prevalence of Noisy Triplet Correspondence (NTC) in large-scale datasets severely constrains model performance. Existing denoising methods either target binary mismatches or rely on scalar-based point-wise estimation, neglecting rich global structural correlations among sample populations and dynamic value variations during training, thereby yielding suboptimal results. This paper identifies two critical unresolved challenges: Global Structural Inconsistency of Semantic Correlations and Hard Sample Discrimination Uncertainty. To address these, we propose RankVR, a framework designed to construct a robust CIR model via global structure consistency and dynamic value perception. Specifically, we introduce the Global Structure Consistency Perception (GSCP) module, which utilizes the Effective Rank of the Correlation Matrix to decouple clean samples from structural noise. By measuring rank difference, GSCP identifies samples disrupting macroscopic semantic symmetry. Furthermore, we develop the Adaptive Semantic Value Calibration (ASVC) module to distinguish high-value hard clean samples. By integrating training potential and reliability, it dynamically quantifies the semantic value of each triplet, ensuring effective utilization of hard samples while suppressing noise characterized by logical conflicts. Extensive experiments on the FashionIQ and CIRR benchmark datasets demonstrate that RankVR significantly outperforms existing state-of-the-art methods, validating its superior robustness in noisy environments.

15.
arXiv (CS.AI) 2026-06-17

Surrogate Assisted Pedestrian Protection Design via a Foundation Model Orchestrated Workflow

arXiv:2606.17577v1 Announce Type: new Abstract: AI-driven engineering workflows face particular challenges in crash safety design: unlike aerodynamics, crash events involve highly nonlinear contact dynamics, material nonlinearity, and discrete state transitions that are difficult to capture with data-driven surrogate models. To the best of our knowledge, we present the first foundation model–orchestrated workflow for crash safety design that enables surrogate-assisted exploration for pedestrian protection, reducing evaluation time from hours per CAE simulation to seconds. The workflow integrates four components: (1) a surrogate trained on CAE crash simulations to predict pedestrian leg injury metrics from design parameters, achieving an average $R^2=0.87$ and providing distribution-free conformal prediction intervals; (2) multiobjective evolutionary search (NSGA-II) to discover diverse feasible parameter sets under user-specified constraints; (3) a morphing-based geometry generator that maps parameters to topology-preserving 3D shapes; and (4) a natural-language interface in which an LLM orchestrates the workflow and a vision–language model supports semantic comparison of generated designs. In an automotive front-bumper case study, the workflow produces 35 distinct safety-compliant alternatives from a single exploration, a process that would require weeks with conventional CAE iteration. These results suggest that foundation models can serve as integration layers between ML surrogates and physics-based simulation, helping bring AI capabilities to safety-critical engineering domains.

16.
medRxiv (Medicine) 2026-06-12

Genetic basis of dynamic brain states reveals cellular and disease associations

Dynamic resting-state fMRI captures the time-varying patterns of brain activity that are obscured by static approaches. Hidden Markov Models (HMMs) characterise these dynamics as recurring whole-brain states and quantify their fractional occupancy (FO), the proportion of time spent in each state, yet the biological basis of inter-individual variation in FO remains unclear. Using data from 52,335 White UK Biobank participants, with replication in East and South Asian subsamples, this study examined the heritability, cellular and neurotransmitter basis of brain states, and their links with complex phenotypes. FO was significantly heritable and enriched for neuronal populations, particularly glutamatergic and GABAergic signalling. Analyses identified shared and state-specific loci and revealed genetic correlations, colocalisation, and potential causal relationships between FO and several phenotypes, including educational attainment, sleep duration, and disease risk. These findings establish dynamic brain states as biologically grounded intermediate phenotypes, linking genetic variation to neural dynamics, diseases and traits.

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

Retrofitters, pragmatists and activists: Public interest litigation for accountable automated decision-making

arXiv:2511.03211v4 Announce Type: replace-cross Abstract: This paper examines the role of public interest litigation in promoting accountability for AI and automated decision-making (ADM) in Australia. Since ADM regulation faces political and geopolitical headwinds, effective governance will have to rely on the enforcement of existing laws. Drawing on interviews with Australian public interest litigators, technology policy activists, and technology law scholars, the paper positions public interest litigation as part of a larger ecosystem for transparency, accountability and justice with respect to ADM. The paper explores the tactics and strategies of what one participant described as 'retrofitting' old laws to ADM. These go beyond creative legal argumentation, to encompass practices of community-building, collaboration on theories of change, canny selection of clients and causes of action, and the alignment of the interests of stakeholders in litigation. Naturally, the paper also contends with the limits of these strategies, and of the Australian legal system. Where limits are, however, capable of being overcome, the paper presents findings on urgent needs: the enabling institutional arrangements without which effective litigation and accountability will falter. The paper is relevant to law and technology scholars; individuals and groups harmed by ADM; public interest litigators and technology lawyers; civil society and advocacy organisations; and policymakers.

18.
arXiv (CS.CV) 2026-06-19

Vortex: Multi-Modal Fusion System for Intelligent Video Retrieval

This paper presents Vortex, the multimodal video retrieval system developed by our team, FocusOnFun, for the Ho Chi Minh City AI Challenge 2025, designed to advance intelligent multimedia search and temporal reasoning. The system integrates adaptive keyframe extraction, multimodal metadata generation from vision-language and speech models, and a hybrid retrieval strategy that fuses CLIP and SigLIP2 embeddings through Reciprocal Rank Fusion to balance global and fine-grained semantics. To enhance interactivity, Vortex incorporates Rocchio-based relevance feedback and a multi-stage temporal search mechanism for sequential event alignment. Built on Milvus and Elasticsearch, the architecture enables scalable indexing and efficient retrieval. Evaluated in the official competition, our FocusOnFun team's system achieved a score of 79.6/88 (90.5\%) in the Preliminary Round and was further evaluated in the Final Round, achieving an `Excellent' overall performance with `Outstanding' results in the question-answering (QA) task. This demonstrating the complementary strengths of CLIP and SigLIP2 and confirming the effectiveness of the hybrid retrieval approach. The system establishes a robust foundation for future research in intelligent, context-aware, and interactive video retrieval.

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

Clarify Before You Draw: Proactive Agents for Robust Text-to-CAD Generation

arXiv:2602.03045v2 Announce Type: replace Abstract: Large language models have recently enabled text-to-CAD systems that synthesize parametric CAD programs (e.g., CadQuery) from natural-language prompts. In practice, however, geometric descriptions can be under-specified or internally inconsistent: critical dimensions may be missing and constraints may conflict. However, existing fine-tuned models tend to reactively follow the user instructions and hallucinate dimensions when the text is ambiguous. To address this, we propose a proactive agentic framework for text-to-CadQuery generation, named as ProCAD, that resolves specification issues before code synthesis. Our framework pairs a proactive clarifying agent, which audits the prompt and asks targeted clarification questions only when necessary to produce a self-consistent specification, with a CAD coding agent that translates the specification into an executable CadQuery program. We fine-tune the coding agent based on a curated high-quality text-to-CadQuery dataset and train the clarifying agent via agentic SFT on clarification trajectories. Experiments show that proactive clarification significantly improves robustness to ambiguous prompts while keeping interaction overhead low. ProCAD outperforms frontier closed-source models, including Claude Sonnet 4.5, reducing the mean Chamfer distance by 79.9% and lowering the invalidity ratio from 4.8% to 0.9%. Our code and datasets are made publicly available on https://github.com/BoYuanVisionary/Pro-CAD.

20.
bioRxiv (Bioinfo) 2026-06-12

From Proteome Mining to Structural Validation: Phosphopyruvate Hydratase as a Structurally Tractable Drug Target in Kinetoplastid Parasites

Chagas disease, caused by Trypanosoma cruzi, demands novel therapeutic strategies that overcome the toxicity and limited efficacy of current treatments. To address this need, herein we report an integrative, target-centric strategy that combines parasite proteome mining, structural modeling, and experimental validation. Functional enrichment and druggability analyses identified phosphopyruvate hydratase (PPH) as a promising candidate due to its essential metabolic role and limited similarity to human homologs. Notably, proteome mining revealed the presence and conservation of PPH across kinetoplastid parasites, including Leishmania donovani, supporting its evaluation beyond T. cruzi. For the selected PPH sequences, AlphaFold-derived three-dimensional models underwent extensive molecular dynamics refinement, yielding stable conformational ensembles suitable for structure-based studies. Using this validated model, virtual screening of the Latin American Natural Products Database - LANaPDB - identified aptosimon as a top-ranked compound candidate. Molecular dynamics simulations further showed ligand-dependent binding behavior, suggesting alternative binding modes distinct from the canonical substrate configuration. In vitro assays demonstrated consistent antiparasitic activity against intracellular T. cruzi amastigotes (IC50 = 3.52 ug/mL) and Leishmania donovani promastigotes (IC50 = 13.06 ug/mL), supporting the biological relevance of the aptosimon-related lignan chemotype, hinokinin, across two kinetoplastid parasite models. Together, these results support PPH as a structurally tractable and biologically relevant candidate target, while identifying an aptosimon-related lignan chemotype, represented experimentally by hinokinin, as a cross-species antiparasitic scaffold that warrants further biochemical target-validation studies.

21.
bioRxiv (Bioinfo) 2026-06-12

Generalisable tissue-wide molecular reconstruction from histology

Spatial transcriptomics technologies measure gene expression within intact tissues but remain difficult to scale across large tissue sections and patient cohorts. Consequently, many studies rely on tissue microarrays (TMAs) or sparse spatial profiling designs, where molecular measurements are available for only limited tissue regions and are often generated using heterogeneous gene panels. Existing H&E to spatial gene expression prediction methods remain challenged by sparse molecular measurements, partially overlapping gene panels and tissue-wide reconstruction across heterogeneous spatial datasets. Here, we present GHIST+, a framework for tissue-wide reconstruction of single-cell molecular states from H&E histology. GHIST+ integrates cellular morphology, local tissue context and shared tissue representations to extend sparse molecular measurements into tissue-wide molecular maps across heterogeneous spatial datasets. Across multiple cancer types and GTEx breast tissues, GHIST+ reconstructs biologically meaningful tissue-wide molecular organisation from sparse TMA-derived measurements while preserving spatial tissue structure, cell-type organisation and age-associated tissue states across cancer and non-cancer settings. GHIST+ establishes a scalable framework for transforming sparse spatial profiling experiments into tissue-wide molecular maps, enabling cohort-scale molecular reconstruction from routine histology under heterogeneous spatial transcriptomic settings.

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

Veriphi: Attack-Guided Neural Network Verification with Dataset-Dependent Training Methods

arXiv:2606.18454v1 Announce Type: cross Abstract: We present Veriphi, a GPU-accelerated neural network verification system that combines fast adversarial attacks with formal bound certification using alpha,beta-CROWN methods. Through systematic experiments on MNIST and CIFAR-10 using three training methodologies (standard, adversarial, certified), we demonstrate that training method effectiveness is fundamentally dataset-dependent. Interval Bound Propagation (IBP) achieves 78% certified accuracy on simple MNIST (784 dimensions) but provides negligible certification performance on the more complex CIFAR-10 dataset, where PGD adversarial training dominates with 94% certification at small perturbations. We achieve 5x verification speedup through attack-guided falsification and scale our approach to production-size models (105.8M parameters) for real-world aerospace logistics optimization. Our results challenge the assumption that certified training universally outperforms adversarial training, showing context matters critically for verification strategy selection.

23.
arXiv (CS.AI) 2026-06-17

Agentic Discovery of Non-Canonical Antimicrobial Peptides with AMPGAN v3

arXiv:2606.17127v1 Announce Type: cross Abstract: Antimicrobial resistance causes to over a million deaths annually. Antimicrobial peptides (AMPs) are a promising solution, but generative AMP models are not yet ready to design peptides with non-natural amino acids and/or chemical modifications, which are essential for real-world peptide drugs. We present AMPGAN v3, a multi-objective conditional GAN that expands the generative vocabulary to D-amino acids and N/C-terminus modifications such as amidation. By separating adversarial and activity-aware supervision across two specialized discriminators, AMPGAN v3 substantially improves training stability and outperforms prior generative AMP models on external classifiers. We validated five candidates spanning three structural classes in vitro; two showed activity against Gram-positive strains, with the best candidate reaching MIC 8 {\mu}g/mL against B. subtilis. To support downstream curation, we further present PepCraft, a multi-agent framework for end-to-end AMP discovery in which a Planning Agent orchestrates specialized executors for generation, filtering, and verification. Its prioritization recommendations align with our in vitro outcomes. Together, these contributions let us examine, on a small but real scale, how generative and agentic AI compose in therapeutic peptide discovery. Code: https://github.com/marszzibros/AMPGANv3

24.
arXiv (CS.AI) 2026-06-17

Ensemble RL through Classifier Models: Enhancing Risk-Return Trade-offs in Trading Strategies

作者:

arXiv:2502.17518v3 Announce Type: replace-cross Abstract: This paper presents a comprehensive study on the use of ensemble Reinforcement Learning (RL) models in financial trading strategies, leveraging classifier models to enhance performance. By combining RL algorithms such as A2C, PPO, and SAC with traditional classifiers like Support Vector Machines (SVM), Decision Trees, and Logistic Regression, we investigate how different classifier groups can be integrated to improve risk-return trade-offs. The study evaluates the effectiveness of various ensemble methods, comparing them with individual RL models across key financial metrics, including Cumulative Returns, Sharpe Ratios (SR), Calmar Ratios, and Maximum Drawdown (MDD). Our original experimental results demonstrate that ensemble methods often outperform base models in terms of risk-adjusted returns, providing better management of drawdowns and overall stability. However, both the original analysis and the additional reproduction reported in this version show that ensemble performance is sensitive to the choice of variance threshold \(\tau\), classifier group, RL-agent pair, and market universe. The reproduction evidence strengthens the conclusion that classifier-assisted ensemble selection can improve robustness, while also clarifying that the advantage is conditional rather than automatic across all datasets. This study emphasizes the value of combining RL with classifiers for adaptive decision-making, with implications for financial trading, robotics, and other dynamic environments.

25.
arXiv (CS.AI) 2026-06-18

SHIFT: Semantic Harmonization via Index-side Feature Transformation for Multilingual Information Retrieval

arXiv:2606.18801v1 Announce Type: cross Abstract: With the rapid expansion of massive multilingual corpora, Multilingual Information Retrieval (MLIR) has emerged as a critical technology for global information access. MLIR enables users to retrieve semantically relevant documents from multilingual text collections using a single-language query. However, recent multilingual dense retrieval models often exhibit a strong preference for documents in the same language as the query. This leads to severe language bias, where top-ranked results are dominated by documents of specific languages, even when documents in other languages contain more semantically relevant information. To address this issue, we propose SHIFT, a training-free method applicable in the indexing stage. Specifically, SHIFT utilizes parallel translation pairs to estimate a relative language vector for each target language with respect to a source language. Subsequently, SHIFT corrects the language-specific offset by subtracting this relative language vector from document embeddings during indexing. Our comprehensive evaluation across four MLIR benchmarks and diverse dense retrieval models confirms that SHIFT can effectively mitigate language bias and enhance MLIR performance.