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01.
arXiv (CS.AI) 2026-06-17

LLMCodec: Adapting Video Codecs for Efficient Weight Compression of Large Language Models

arXiv:2606.05861v2 Announce Type: replace-cross Abstract: The rapid development of large language models(LLMs) has led to remarkable advances in natural language processing. However, the increasing scale of these models introduces substantial challenges in terms of storage, transmission, and deployment. Though great efforts have been devoted to model compression and quantization, existing methods often rely on fine-tuning or calibration data, which exhibit limited generalization across different tensor types. In this paper, we argue that video codecs offer a promising solution for LLM compression, due to their inherent compatibility with matrix structured data, configurable compression strategies, and the availability of highly optimized, off-the-shelf implementations. Therefore, we present LLMCodec, a video codec-based LLM compression method that integrates affine quantization with the recent VVC/H.266 video codec. Beyond VVC, we further compare a range of video codecs and encoding profiles to evaluate their impact on compression performance. Experiments on different models demonstrate the robustness and generality of LLMCodec. Notably, on LLaMA-3-8B at 2-bit precision, LLMCodec reduces perplexity by over 1.5x and improves downstream task accuracy by 21% compared with the existing method.

02.
arXiv (CS.CV) 2026-06-11

Benchmarking Cross-Domain Audio-Visual Deception Detection

Automated deception detection is crucial for assisting humans in accurately assessing truthfulness and identifying deceptive behavior. Conventional contact-based techniques, like polygraph devices, rely on physiological signals to determine the authenticity of an individual's statements. Nevertheless, recent developments in automated deception detection have demonstrated that multimodal features derived from both audio and video modalities may outperform human observers on publicly available datasets. Despite these positive findings, the generalizability of existing audio-visual deception detection approaches across different scenarios remains largely unexplored. To close this gap, we present the first cross-domain audio-visual deception detection benchmark, that enables us to assess how well these methods generalize for use in real-world scenarios. We used widely adopted audio and visual features and different architectures for benchmarking, comparing single-to-single and multi-to-single domain generalization performance. To further exploit the impacts using data from multiple source domains for training, we investigate three types of domain sampling strategies, including domain-simultaneous, domain-alternating, and domain-by-domain for multi-to-single domain generalization evaluation. We also propose an algorithm to enhance the generalization performance by maximizing the gradient inner products between modality encoders, named ``MM-IDGM". Furthermore, we proposed the Attention-Mixer fusion method to improve performance, and we believe that this new cross-domain benchmark will facilitate future research in audio-visual deception detection.

03.
arXiv (CS.LG) 2026-06-16

MolE-RAG: Molecular Structure-Enhanced Retrieval-Augmented Generation for Chemistry

arXiv:2606.05693v2 Announce Type: replace Abstract: Large language models (LLMs) have shown promise for molecular property prediction, but their ability to reason over chemical structures remains limited, as molecular representations such as SMILES differ substantially from the natural language on which LLMs are primarily trained. To bridge this semantic and chemical knowledge gap, we propose MolE-RAG, a training-free, molecule-centric retrieval-augmented generation framework for LLM-based molecular property prediction. MolE-RAG augments each prediction with three complementary sources of inference-time context: retrieved chemistry literature, molecule-specific information including compound synonyms, identifiers, functional group annotations, and physicochemical descriptors, and structurally similar molecules retrieved from the training set. We evaluate MolE-RAG across nine molecular property prediction tasks using proprietary, chemistry-specialized, and open-source LLMs. Across general-purpose LLMs, MolE-RAG improves ROC-AUC by up to 28 percentage points on classification tasks and reduces regression RMSE by up to 67% relative to a SMILES-only baseline. We further find that the utility of each context source varies across models and tasks, with different models benefiting most from textual retrieval, molecular context, or structural retrieval. These results suggest that molecule-centric retrieval can improve LLM-based molecular property prediction without model fine-tuning while providing a flexible framework for integrating heterogeneous chemical knowledge at inference time.

04.
arXiv (CS.CV) 2026-06-18

Reasoning as Intersection: Consensus-Frame Alignment for Visual Focus in Video-MLLMs

Reinforcement learning has improved the reasoning ability of large language models, but applying outcome-only rewards to video multimodal large language models (Video-MLLMs) provides limited guidance on which visual evidence should support the answer. Inspired by multisensory integration, where consistent cues can enhance the salience and reliability of perceptual estimates, we introduce Consensus Frame GRPO (CF-GRPO), a temporal-annotation-free process-level reward framework for evidence-aware video reasoning. CF-GRPO constructs a consensus frame prior from intrinsic video cues, including temporal coverage, scene-transition cues, and query-conditioned visual relevance. It then computes a model-side frame-use score from visual and response representations and optimizes their agreement through the Consensus Frame Reward (CFR). With salience-aware sparse aggregation and distribution sharpening, CFR provides a high-contrast reward signal without requiring human temporal annotations. Experiments show that VideoCFR achieves competitive performance across complex video reasoning benchmarks and improves several metrics over representative Video-MLLM and RL baselines, while the consensus prior provides an interpretable view of the evidence frames emphasized during training. The implementation is available at https://github.com/1Pansy/VideoCFR.

05.
arXiv (CS.CV) 2026-06-18

Fuzzy-Geometric Branch-Point Modeling for Structure-Aware Augmentation of Handwritten Chinese Characters

Data scarcity and structural distortion significantly limit handwriting recognition in high-security authentication. Existing augmentation methods often cause topological and morphological damage, particularly when processing complex Chinese characters where stroke intersections, ligatures, and sharp turns render traditional branch-point detection unreliable. To address this, this paper proposes a fuzzy geometry-driven structure-aware (FGSA) augmentation framework. We model branch points as fuzzy sets within the skeleton space, constructing a continuous branch-point membership field by integrating topological neighborhood evidence with direction field divergence. This membership field is adaptively optimized via an unsupervised surrogate objective, enabling robust stroke decoupling without manual annotation. Finally, kinematically-aligned samples are synthesized through parameterized cubic Bézier reconstruction and multi-strategy perturbations, ensuring a balance between structural fidelity and sample diversity. Moreover, we establish LZUSig, a large-scale, highly challenging dataset specifically dedicated to fine-grained structural degradation in Chinese handwritten signatures. Extensive experiments on CASIA-HWDB1.1, ChiSig, and LZUSig demonstrate that FGSA significantly reduces the word-level error rate ($\Delta$WER), achieving optimal recognition gains over the compared baselines. More importantly, it strikes a robust trade-off among task gain, structural fidelity, and discriminative feature preservation, offering a highly controllable solution for handwriting augmentation.

06.
medRxiv (Medicine) 2026-06-19

Performance of family history-based colorectal cancer screening criteria by race and age at diagnosis in the Disparities and Cancer Epidemiology (DANCE) study

Importance: Family history (FH) and age are the primary criteria employed for early colorectal cancer (CRC) risk stratification. We evaluated how well these criteria identify individuals diagnosed with CRC across age and racial groups. Objective: To evaluate the performance of FH and age based screening criteria for identifying individuals with CRC, with attention to differences by race and age at diagnosis. Design, Setting, and Participants: This case control and case only analysis used data from the Disparities and Cancer Epidemiology (DANCE) cohort, a population based study of invasive CRC cases diagnosed from 2013 to 2022, recruited through the Metropolitan Detroit Cancer Surveillance System and the Louisiana Tumor Registry. Analyses included 1,158 non-Hispanic Black (NHB) and non-Hispanic White (NHW) CRC cases and 1,434 cancer-free controls from the Inflammation Health and Lung Epidemiology (INHALE) study, enrolled from the same Detroit catchment area. Data were analyzed in 2025. Exposures: Self reported cancer FH among first-degree (FD) relatives and grandparents, summarized into three FH-based screening criteria: at least one FD relative with CRC (colon early-screening criterion), any FH of Lynch syndrome related cancers, and meeting NCCN criteria for Lynch syndrome genetic testing. Main Outcomes and Measures: Proportion of cases meeting each FH based screening criterion stratified by race and age at diagnosis (

07.
PLOS Computational Biology 2026-06-02

Data-driven model reveals increased stability of CAG-expanded <i>huntingtin</i> RNA due to MID1 binding

Authors:

by Yuhong Liu, Annika Reisbitzer, Domagoj Dorešić, Jan Hasenauer, Sybille Krauß, Tatjana Tchumatchenko RNA-binding proteins (RBP) are important regulators of RNA metabolism. In neurodegenerative disorders such as Huntington’s Disease (HD), disrupted RBP-RNA interactions contribute to neuronal dysfunction. One such RBP, Midline 1 (MID1), has been shown to aberrantly associate with mutant huntingtin (Htt) RNA, enhancing its translation, yet the mechanism driving this effect remains unknown. Here, we develop a computational model to understand the role of MID1. Based on previously published data, our model predicts that MID1 increases the stability of the Htt RNA. We experimentally validate this prediction, showing that overexpression of MID1 significantly prolongs the half-life of mutant Htt RNA. Furthermore, we evaluate model refinements, including clustering of MID1-bound RNA, which allow capturing all key observations in the data. Together, we provide a data-driven framework that underlines the importance of RBP-RNA interaction in post-transcriptional regulation. This framework also shows how individual molecular reactions jointly determine RNA stability and protein levels in HD.

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

Learning-Augmented Approximation for Unrelated-Machines Makespan Scheduling

arXiv:2606.13133v1 Announce Type: cross Abstract: Recently, Antoniadis et al. (ICLR 2025) proposed a framework for incorporating predictions to approximate NP-hard selection problems. Despite its simplicity, this approach tightly matches theoretical lower bounds, making its generalization highly compelling. We address an open question raised in the work of Antoniadis et al., concerning the extension of this approach to other important problems outside the class of selection problems, such as scheduling. We develop a learning-augmented algorithm for the makespan minimization problem on unrelated machines, denoted by $R\|C_{\max}$. By using predictions of heavy job assignments, we achieve a polynomial-time $(1+\varepsilon)$-approximation for accurate predictions that smoothly degrades to a worst-case 2-approximation as the error increases. We conclude our work with an empirical analysis of our method.

09.
arXiv (quant-ph) 2026-06-19

Observation of alignment tensor effects in metastability-exchange collisions with highly polarized 3He ensembles

arXiv:2606.20330v1 Announce Type: new Abstract: Highly polarized 3He ensembles prepared by metastability-exchange optical pumping (MEOP) have been widely used in precision measurements and fundamental physics. Metastability-exchange (ME) collisions, serving as the basis of MEOP, are traditionally described in terms of atomic orientation, while the significant contributions of metastable alignment tensor at high polarization remain unexplored. In this work, we develop a linearized model under mean-field approximation to investigate alignment tensor effects in highly polarized 3He , which originate from the metastable F = 3/2 manifold and are revealed through ME-induced relaxation and frequency shift. By means of free-induction-decay (FID) measurements, a pronounced dependence on nuclear polarization is experimentally observed in the response of the ground-state-metastable hybrid 3He ensembles to the external magnetic field. Furthermore, after obtaining the characteristics of tensor-induced phenomena, we demonstrate good agreement between the experiment and the theory. This work advances the understanding of nuclear spin dynamics in highly polarized 3He using MEOP. It further provides applications in systematic error correction of high-accuracy magnetometry, as well as in optimal protocol for the generation of nuclear spin-squeezed states.

10.
medRxiv (Medicine) 2026-06-17

Hormonal Contraceptives Drive Genital Lipid Metabolism Reprogramming and Susceptibility to HIV Infection

Heterosexual genital HIV transmission is a major driver of new infections, particularly in women, making them disproportionately vulnerable to HIV acquisition. Previous studies have associated injectable hormonal contraceptives (HC) with increasing susceptibility to HIV. Yet, the underlying molecular mechanism remains incompletely understood. Given the structural and signaling role of lipids in the female genital tract, cervicovaginal lipidomic profiling has the potential to reveal the mechanistic interplay among HC, lipidome, and HIV susceptibility in the female genital tract. We conducted untargeted cervicovaginal lipidomics study in a cohort of high-risk, HIV-negative, Kenyan sex workers who were using injectable depot medroxyprogesterone acetate (DMPA), oral contraceptive pill (OCP), or no hormonal contraception (NH). Genital lipids were quantitatively analyzed using liquid chromatography-mass spectrometry (LC-MS) and bioinformatics platforms. A total of 1045 lipid species were identified in the cervicovaginal lavage samples. Injectable DMPA significantly downregulated major structural and signaling membrane lipids, including phospholipids, ceramides, sphingomyelins, and glycosphingolipids (p

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

Federated Medical Image Segmentation under Real-World Label Noise: A Benchmark Suite for Noisy Label Learning Method Selection

While federated learning (FL) enables collaborative medical image segmentation without centralizing sensitive data, real-world deployment is frequently complicated by cross-site label imperfections such as contour disagreement, missing or additional structures, and confused labels. Federated noisy label learning (FNLL) aims to mitigate these effects, yet remains underused in practice as existing evidence is largely based on synthetic noise, simplified settings, and limited real-world noisy evaluation. We address this gap by introducing a benchmark suite that combines diverse real-world noisy datasets, deployment-relevant client-noise scenarios, and label-noise-targeted evaluation to support systematic FNLL assessment and informed method selection. The suite combines curated real-world noisy medical image segmentation datasets from diverse sources with a comprehensive federated segmentation framework including various client-noise scenarios and noise-targeted evaluation. The presented suite provides a realistic and discriminative basis for FNLL evaluation in medical image segmentation and establishes a reusable foundation for fair benchmarking, dataset-specific label-noise characterization, and future method development under realistic federated settings. Code is available at https://github.com/MIC-DKFZ/FedSegNoiseBench.

12.
arXiv (CS.LG) 2026-06-16

PhysGuard: Fisher-Guided Gradient Projection for Sim-to-Real Neural PDE Surrogates

arXiv:2606.16602v1 Announce Type: new Abstract: Neural operator models trained on simulation data often lose accuracy when applied to experimental measurements due to the sim-to-real gap. Standard fine-tuning with limited real data can reduce this gap, but it may also damage the core physics-relevant representations learned during pretraining. Although knowledge-preserving adaptation has been widely investigated in vision or language tasks, it remains unclear whether these methods are suitable for neural operators whose architectures and protected knowledge are fundamentally different. Neural operators need to preserve core-scale physical structures rather than semantic or visual features. We propose PhysGuard, a physics-preserving framework for accurate sim-to-real adaptation of neural operators. Specifically, PhysGuard uses the empirical Fisher Information Matrix computed on simulation data to identify physics-critical parameter directions, then restricts fine-tuning updates to directions that do not interfere with them. A layer-wise Gram-matrix formulation makes this efficient for models with millions of parameters, while an adaptive threshold automatically determines the protected subspace size. A spectral probe experiment shows that the dominant Fisher directions are strongly associated with low-frequency output structures. Experiments on benchmark across four neural operator architectures and different physical systems show that PhysGuard performs strongly on most evaluation metrics compared to baselines. The benefits are most evident under severe domain shift, where it reduces low-frequency error by up to 32\% compared to standard fine-tuning while maintaining adaptability. Our code is available at https://github.com/ZhouChaunge/PhysGuard.

13.
arXiv (quant-ph) 2026-06-17

Quantum Computing Algebra (QCA), the theory and implementation

arXiv:2606.17621v1 Announce Type: new Abstract: We present a real geometric algebra framework designed for the direct translation of the Dirac formalism into geometric algebra representations. Unlike previous approaches based on positive-definite signatures, QCA employs a split-signature construction that enables a natural realization of quantum states and operators while simplifying computational implementation. We further present an implementation of QCA using the GAALOP software and show how quantum gates and multi-qubit systems can be efficiently represented and generated computationally. As an application, we demonstrate the use of QCA in quantum game theory, where the real-algebraic formulation provides computational advantages for modeling entangled strategies and quantum interactions. The proposed framework establishes a practical bridge between the abstract formalism of quantum computation and efficient geometric algebra implementations.

14.
arXiv (CS.AI) 2026-06-17

First, do NOHARM: towards clinically safe large language models

arXiv:2512.01241v3 Announce Type: replace-cross Abstract: Large language models (LLMs) are routinely used by physicians and patients for medical advice, yet their clinical safety profiles remain poorly characterized. We present NOHARM (Numerous Options Harm Assessment for Risk in Medicine), a 1,100-task benchmark of primary care-to-specialist consultation cases to measure the frequency and severity of harm from LLM-generated medical recommendations. NOHARM covers 10 specialties, with 12,747 expert annotations for 4,249 clinical management options. Across 28 LLMs, recommendations carried the potential for severe harm in up to 22.6% of cases, with errors of omission accounting for more than 80% of severe errors. In a randomized trial of 101 generalist physicians, human benchmark performance significantly improved with AI assistance, yet physicians remained far from realizing the potential of AI tools, frequently ignoring essential advice surfaced by AI. Safety performance tracked general-intelligence and medical-knowledge benchmarks across the full range of models but decoupled at the frontier. Despite strong performance on existing evaluations, widely used AI models can produce medical advice with the potential for severe harm at non-trivial rates, highlighting the importance of explicit measurement of clinical safety.

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

Implicit Reasoning for Large Language Model-based Generative Recommendation

Large Language Models (LLMs) are increasingly adopted as backbones for Generative Recommendation (GR), promising access to pretrained world knowledge. Yet reliably invoking this knowledge for GR remains poorly understood. A key obstacle is that LLM-based GR typically represents items with Semantic IDs (SIDs), disrupting LLMs' natural-language reasoning interface because these tokens are unseen by the LLM during pretraining. Existing approaches address this with expensive multi-stage pipelines that ground SIDs and elicit explicit rationales, but offer limited insight into when and why each stage is necessary. In this work, we systematically decompose explicit reasoning training pipelines for LLM-based GR, revealing three key limitations: weakened world-knowledge verbalization, misalignment between SID and natural-language token embedding spaces, and sensitivity to rationale quality, all of which hurt explicit reasoning performance. To circumvent these issues, we propose PauseRec, a lightweight implicit reasoning paradigm tailored for GR. PauseRec is exceptionally practical, avoiding costly reasoning trace acquisition and reasoning alignment training, leading to a multitude of benefits: (1) it outperforms standard explicit CoT methods by up to 6.22%, (2) it reduces training cost by up to 65% GPU hours, and (3) it speeds up inference by up to 71.3%. These results position PauseRec as a lightweight alternative to explicit rationale generation, enabling more effective and efficient LLM-based GR.

16.
arXiv (CS.AI) 2026-06-12

Agents-K1: Towards Agent-native Knowledge Orchestration

arXiv:2606.13669v1 Announce Type: new Abstract: Current LLM-based research agents have advanced through agent orchestration, yet largely overlook scientific knowledge orchestration. Existing works often reduce papers to abstracts, surface mentions, and flat \texttt{cites} edges, omitting key entities, claims, evidence, mechanisms, and method lineages essential for scientific reasoning. To this end, we introduce Agents-K1, an end-to-end knowledge orchestration pipeline that converts raw documents into agent-native scientific knowledge graphs. Agents-K1 integrates three components under a unifying theoretical foundation: a multimodal parser whose five-module schema captures entities, multimodal evidence, citations, and typed inter-entity relations across the full paper rather than abstracts alone; a 4B information-extraction backbone trained with GRPO under a rule-based reward; and a graphanything CLI, a tri-source agent interface that unifies web search, multimodal graph retrieval, and cross-document traversal. On top of this, we process 2.46 million scientific papers across six subjects to produce Scholar-KG, of which we release a one-million-paper subset, and the full Scholar-KG is accessible via the SCP link below. The same pipeline can be extended to general-domain corpora and to schema-conformant data synthesis. Extensive experiments demonstrate that Agents-K1 achieves superior performance in scientific information extraction, knowledge graph construction, and multi-hop scientific reasoning.

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

HemExp: Clinically-Guided Latent Diffusion for Modeling Hematoma Expansion

Hematoma expansion (HE) after spontaneous intracerebral hemorrhage (ICH) is a major determinant of acute triage and treatment decisions in neurosurgical care. However, most existing methods provide either a binary expansion risk or a single follow-up volume, limiting uncertainty-aware decisions. We introduce HemExp, a clinically-guided latent diffusion model that generates patient-specific follow-up non-contrast CT images, along with segmentations of intraparenchymal and intraventricular hemorrhage. Generation is conditioned on baseline imaging, clinical variables, and an explicit expansion indicator, enabling controllable simulation of realistic clinical scenarios. HemExp uses a hemorrhage-aware multi-head variational autoencoder and models progression as the difference between baseline and follow-up latent representations with a conditional diffusion model. The model is trained on paired scans from 450 patients across multiple centers and evaluated on 107 patients from a held-out institution. HemExp produces spatial HE probability maps by generating multiple synthetic follow-up images per patient to estimate distributions of plausible follow-up hematoma volumes. Perturbing clinical inputs such as symptom-onset-to-imaging time or anticoagulant status shifts the predicted follow-up volume distribution. HemExp extends binary predictors and demonstrates robust estimation of clinically relevant outcomes in the imaging space, such as hematoma volume, intraventricular involvement, and mass effects. Overall, our results support controllable latent diffusion as a promising direction for uncertainty-aware modeling of early ICH progression.

18.
arXiv (CS.LG) 2026-06-11

Counterexample Guided Learning in the Large using Reasoning Agents

arXiv:2606.11521v1 Announce Type: new Abstract: LLMs and LLM agents should improve when given feedback, but identifying when they are able to do so is difficult: feedback is heterogeneous, domain-specific, and difficult to control. We approach this challenge by asking LLMs to perform regular-expression induction, a classical symbolic learning problem where precise mechanisms for feedback exist in the form of counterexamples. In counterexample-guided learning, a learner (LLM) proposes candidate regular expressions from positive/negative-labeled strings, and the teacher (verifier) returns counterexamples showcasing the difference between the candidate and target languages. We identify novel counterexample-guided refinement strategies that enable effective regex learning, such as regularization and symbolic counterexample clusters. We also explore agentic strategies such as reflection and repair loops. Empirically, we find that verifier feedback substantially improves sample efficiency on challenging regex-induction tasks, reducing the number of labeled examples required and enabling learning of complex target expressions where standard prompting fails. For example, on the hardest task groups, our counterexample-guided framework improves success from 3.2% to 38.1% and from 38.9% to 74.1% on two different regex domains. These results suggest that LLMs can benefit from rich feedback beyond treating it as additional data, opening the door for robust verifier-guided methods for LLM-based program synthesis and formal reasoning.

19.
medRxiv (Medicine) 2026-06-11

Plasma protein prioritisation in rheumatoid arthritis reveals druggable targets and shared biology with cardiovascular diseases

Abstract Background Rheumatoid arthritis (RA) is an autoimmune inflammatory disease with complex and incompletely understood molecular mechanisms. Understanding circulating proteins associated with RA may improve understanding of disease biology and clarify its pathological links with cardiometabolic comorbidities. Methods A proteome-wide two-sample Mendelian randomisation (MR) drug target analysis was conducted using plasma proteins measured in 54,219 participants from the UK Biobank Pharma Proteomics Project as exposures and RA and cardiometabolic diseases as the outcomes. Summary statistics for RA included 53,663 cases and 1,070,200 controls. Colocalisation analysis was performed to confirm shared single causal variants and prioritise RA proteins supported by both MR and colocalisation. The prioritised proteins were then evaluated in the Accelerating Medicines Partnership RA Phase II synovial single-cell dataset for cell-type expression patterns. Druggability was then assessed followed by analysis of genetic overlap between RA-associated proteins and cardiometabolic diseases. Results 37 plasma proteins had a causal effect on RA risk, supported by combined evidence from MR and conditional colocalisation. In synovial tissue, TPPP3, RARRES2, AKAP12, and GGT5 were predominantly expressed in stromal and endothelial cell clusters. Druggability assessment identified IFNGR2, IL6R, CD40, and FCGR2B as Tier 1 targets. However, several biologically relevant proteins, including RARRES2, AKAP12, TPPP3, and SNX2, had limited available druggability data. Genetic overlap analysis demonstrated shared protein signals between RA and cardiovascular diseases, including overlap of RARRES2 and TPPP3 with coronary artery disease (CAD) and FCGR2B with atrial fibrillation (AF). To approximate the therapeutic effect of target inhibition, the direction of effect estimates for proteins showing overlap between RA-CAD and RA-AF was reversed. Conclusion This study identified circulating proteins involved in RA pathogenesis and reveals shared mechanisms between RA and cardiovascular diseases. While some proteins showed clear translational potential targets, several prioritised proteins had limited available druggability information and could not be confidently classified. Addressing these gaps may help identify new targets relevant to RA management. Future work should also use phenome-wide MR studies to evaluate potential on-target adverse effects of protein inhibition across RA-CAD and RA-AF.

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

Loss Landscape Poisoning: Targeted Extraction of Unseen Training Data from LLMs

arXiv:2606.17110v1 Announce Type: cross Abstract: Large Language Models are increasingly trained on proprietary or sensitive data, from private healthcare and financial records to user conversations containing secrets. Ensuring the privacy of such data against extraction attacks has become a central concern. In this paper, we ask whether an attacker who can poison a portion of the training data can facilitate the leakage of a separate target record they have no access to. We answer in the affirmative and show that such leakage can be induced by a poisoning mechanism that reshapes the model's local loss landscape around the target completion. Our key insight is that poisoning to create a sharp loss minimum at the target, surrounded by elevated loss on nearby alternatives, forces the model to memorize the target as the unique low-loss solution in its neighborhood. The attack requires no architectural changes, and generalizes across centralized and federated learning settings. We demonstrate that the attack amplifies privacy leakage across language (up to 100% successful extraction), and vision-language models (up 90% successful extraction). We show that the attack is thwarted when the model is trained to be differentially private. However, we introduce a new attack that directly probes the loss landscape bypassing even differential privacy defenses.

21.
arXiv (CS.CL) 2026-06-15

The Coin Flip Judge? Reliability and Bias in LLM-as-a-Judge Evaluation

Authors:

LLM-as-a-Judge is now widely used to rank model outputs, train reward models, and populate public leaderboards, but its run-to-run reliability remains under-characterized. We study repeated identical evaluations on 29 tasks spanning 10 categories using two OpenAI judge models (GPT-4o-mini and GPT-4.1-mini), with 50 pairwise trials and 50 pointwise trials per question, supplemented by temperature and prompt-sensitivity ablations. Across judges, pairwise preferences flip on average 13.6% of the time, with 28% of questions exceeding a 20% flip rate and one question reaching 56%. GPT-4o-mini also exhibits a significant first-position bias (72% A-majority, p = 0.024). At the same time, mean pointwise score gaps are small (0.19–0.36 on a 10-point scale) and not statistically significant in aggregate, producing a pairwise–pointwise gap: judges frequently choose a winner even when their own scalar scores provide little evidence of a meaningful quality difference. Beyond within-judge instability, cross-judge agreement is only 76% ($\kappa = 0.51$), semantically equivalent prompt templates change majority outcomes in 25% of tested cases, and deterministic decoding reduces but does not eliminate inconsistency. A reliability curve analysis shows that, in our dataset, 11 repeated trials are needed for a majority vote to recover the 50-trial reference verdict with 95% probability on average, rising to 15 for high-variance questions. These findings suggest that single-trial LLM judging is often too noisy for high-stakes evaluation, and that multi-trial aggregation, position randomization, and explicit uncertainty reporting should be standard practice. Because both judges are from a single provider, cross-provider replication remains an important next step.

22.
bioRxiv (Bioinfo) 2026-06-18

A data-driven rediscovery of the specificity-conferring code of adenylation domains in nonribosomal peptide synthetases

Nonribosomal peptide synthetases (NRPSs) are large modular enzymes that assemble structurally diverse peptides, many of pharmacological importance, including antibiotics and immunosuppressants. Within each NRPS module, the adenylation (A) domain selects the substrate to be incorporated, a choice governed by a small set of residues lining the binding pocket. For two decades, computational prediction of A-domain substrate specificity has relied on residue sets - most prominently the Stachelhaus code and the 34-residue "8 Angstrom code" - that were defined by spatial proximity to the substrate rather than by demonstrated predictive value. Here we revisit which residues govern substrate specificity from a purely data-driven perspective. We assembled a non-redundant dataset of 5,366 A-domain sequences (4,693 bacterial and 673 fungal) and used information-theoretic measures to rank alignment positions by their statistical association with substrate identity, without restricting candidate positions to any predefined structural shell. This procedure yielded two compact, kingdom-specific codes: IG15B (15 positions) for bacterial and IG13F (13 positions) for fungal A-domains. Both match or exceed the predictive accuracy of the 34-residue 8 Angstrom code while using fewer than half its positions, and both independently recover the majority of the classical Stachelhaus positions. Notably, our analysis identifies four positions (242, 280, 281, and 284) that lie outside all conventional codes yet carry non-redundant specificity information and co-localize with classical determinants on two helices flanking the binding pocket. These positions provide new candidate sites for the rational engineering of A-domain specificity.

23.
Nature (Science) 2026-06-08

Targeting Cancer-Specific Mutations with RNA-Triggered Chromatin Shredding

Authors:

Genetic mutations that drive cancer often occur in tumor suppressor proteins, including the p53 transcription factor which is altered in ~40-50% of cases1,2. However, current therapies fail to target most such mutations because the mutant proteins typically lack defined drug-binding pockets, and restoring the endogenous function has proven challenging. Here, we programmed CRISPR-Cas12a2, an RNA-guided nuclease with trans-nucleolytic cleavage activities3,4, to selectively kill cancer cells by targeting cancer-specific transcripts. This approach limits cell growth by inducing trans shredding of chromatin, triggering DNA damage responses and cell death. Unlike existing methods, RNA-guided Cas12a2 senses cellular RNA signatures, enabling precise targeting of undruggable mutations. Transcript-activated chromatin shredding provides a new approach to precision disease treatments for undruggable targets.

24.
arXiv (quant-ph) 2026-06-24

Quantum algorithm for Valiant-Vazirani reduction

arXiv:2606.18428v2 Announce Type: replace Abstract: There is growing interest in extensions of the standard model of gate-based quantum computation to include auxiliary degrees of freedom evolving according to a nonlinear Schrödinger equation. By reducing the Boolean satisfiability problem SAT to quantum state discrimination, Abrams and Lloyd argued that the right type of nonlinearity can be used to solve NP and #P problems in polynomial time, at least in an idealized noise-free limit. For practical implementation, however, we are restricted to simulated and emergent nonlinearities, such as that appearing in mean field models for ultracold atoms and similar ensembles. A prominent example is the torsion model, which arises in two-component Bose-Einstein condensates and spin models with all-to-all Ising interaction. But torsion-based state discrimination appears to fall short of solving SAT. Here we close this gap by constructing the filtered oracle of the Valiant-Vazirani theorem, providing a randomized polynomial-time reduction from SAT to UNIQUE SAT, a promise problem where there is at most 1 satisfying assignment. In the noise-free limit, the UNIQUE SAT problem can be solved in polynomial time using torsion nonlinearity. Quantum Valiant-Vazirani reduction is no faster than the efficient classical version, but a fault-tolerant implementation coupled to a nonlinear quantum coprocessor simulating torsion would enable polynomial time solution to NP (but not #P) problems.

25.
arXiv (CS.AI) 2026-06-12

Modern analog computing for solving differential and matrix equations

arXiv:2606.13179v1 Announce Type: cross Abstract: In recent years, driven by the computational demands of data-intensive applications such as artificial intelligence and scientific computing, analog computing has gained renewed interest. Given the diversity of computational tasks and recent advancements in analog CMOS circuits and resistive memory technologies, we refer to the evolving landscape as modern analog computing. In this context, we identify three core computational primitives: solving differential equations, solving matrix equations, and performing matrix-vector multiplications, and we explore the connections among them. We also examine various hardware implementations of these analog computing operators, including those built with discrete components, integrated circuits, and resistive memory devices. Among these, resistive memory arrays emerge as particularly promising due to their implementation efficiency. The paper then surveys recent progress in leveraging modern analog computing to solve differential and matrix equations using both advanced analog CMOS circuits and resistive memory arrays. Finally, we discuss the applications of these circuits, the precision and scalability issues and their potential solutions, the relationship with in-memory computing, and the unique computational complexity of analog computing. This paper provides a unified perspective on analog computing, highlighting its strengths, current developments, and challenges, and positioning it as a pivotal enabler of next-generation computational frontiers.