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01.
arXiv (CS.CL) 2026-06-19

Improving Alignment Between Human and Machine Codes: An Empirical Assessment of Prompt Engineering for Construct Identification in Psychology

Due to their architecture and vast pre-training data, large language models (LLMs) demonstrate strong text classification performance. However, LLM output - here, the category assigned to a text - depends heavily on the wording of the prompt. While literature on prompt engineering is expanding, few studies focus on classification tasks, and even fewer address domains like psychology, where constructs have precise, theory-driven definitions that may not be well represented in pre-training data. We present an empirical framework for optimizing LLM performance for identifying constructs in texts via prompt engineering. We experimentally evaluate five prompting strategies – codebook-guided empirical prompt selection, automatic prompt engineering, persona prompting, chain-of-thought reasoning, and explanatory prompting - with zero-shot and few-shot classification. We find that persona, chain-of-thought, and explanations do not fully address performance loss accompanying a badly worded prompt. Instead, the most influential features of a prompt are the construct definition, task framing, and, to a lesser extent, the examples provided. Across three constructs and two models, the classifications most aligned with expert judgments resulted from a few-shot prompt combining codebook-guided empirical prompt selection with automatic prompt engineering. Based on our findings, we recommend that researchers generate and evaluate as many prompt variants as feasible, whether human-crafted, automatically generated, or ideally both, and select prompts and examples based on empirical performance in a training dataset, validating the final approach in a holdout set. This procedure offers a practical, systematic, and theory-driven method for optimizing LLM prompts in settings where alignment with expert judgment is critical.

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

Certifiable Safe RLHF: Semantic Grounding and Fixed Penalty Constraint Optimization for Safer LLM Alignment

arXiv:2510.03520v2 Announce Type: replace-cross Abstract: Ensuring safety is a foundational requirement for large language models (LLMs). Achieving an appropriate balance between enhancing the utility of model outputs and mitigating their potential for harm is a complex and persistent challenge. Contemporary approaches frequently formalize this problem within the framework of Constrained Markov Decision Processes (CMDPs) and employ established CMDP optimization techniques. However, these methods exhibit two notable limitations. First, their reliance on reward and cost functions renders performance highly sensitive to the underlying scoring mechanism, which must capture semantic meaning rather than being triggered by superficial keywords. Second, CMDP-based training entails tuning dual-variable, a process that is both computationally expensive and does not provide any provable safety guarantee for a fixed dual variable that can be exploitable through adversarial jailbreaks. To overcome these limitations, we introduce Certifiable Safe-RLHF (CS-RLHF) that introduces a cost model trained on a large-scale corpus to assign semantically grounded safety scores. In contrast to the lagrangian-based approach, CS-RLHF adopts a rectified penalty-based formulation. This design draws on the theory of exact penalty functions in constrained optimization, wherein constraint satisfaction is enforced directly through a suitably chosen penalty term. With an appropriately scaled penalty, feasibility of the safety constraints can be guaranteed at the optimizer, eliminating the need for dual-variable updates. Empirical evaluation demonstrates that CS-RLHF outperforms state-of-the-art LLM model responses rendering at-least 5 times efficient against nominal and jail-breaking prompts

03.
arXiv (CS.CV) 2026-06-17

Does the Data Processing Inequality Reflect Practice? On the Utility of Low-Level Tasks

The data processing inequality is an information-theoretic principle stating that the information content of a signal cannot be increased by processing the observations. In particular, it suggests that there is no benefit in enhancing the signal or encoding it before addressing a classification problem. This assertion can be proven to be true for the case of the optimal Bayes classifier. However, in practice, it is common to perform "low-level" tasks before "high-level" downstream tasks despite the overwhelming capabilities of modern deep neural networks. In this paper, we aim to understand when and why low-level processing can be beneficial for classification. We present a comprehensive theoretical study of a binary classification setup, where we consider a classifier that is tightly connected to the optimal Bayes classifier and converges to it as the number of training samples increases. We prove that for any finite number of training samples, there exists a pre-classification processing that improves the classification accuracy. We also explore the effect of class separation, training set size, and class balance on the relative gain from this procedure. We support our theory with an empirical investigation of the theoretical setup. Finally, we conduct an empirical study where we investigate the effect of denoising and encoding on the performance of practical deep classifiers on benchmark datasets. Specifically, we vary the size and class distribution of the training set, and the noise level, and demonstrate trends that are consistent with our theoretical results.

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

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

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

05.
arXiv (CS.LG) 2026-06-12

Deep Sleep Classification via EEG Signal Criticality: A Passive BCI Approach for Sleep-Improvement Neurofeedback

arXiv:2606.13017v1 Announce Type: cross Abstract: Automated sleep staging is a fundamental application of passive Brain-Computer Interfaces (pBCI), decoding spontaneous neural states to enable closed-loop interventions independent of user intent. This study evaluates criticality features derived from Detrended Fluctuation Analysis (DFA) for the specific identification of deep sleep (N3). We analyzed $347,232$ EEG epochs from $290$ older women using UMAP manifold learning to visualize state transitions. Subsequently, six classifiers were benchmarked via 10-fold cross-validation, using balanced accuracy to determine the optimal "state-sensing" engine for neurofeedback.Naive Bayes achieved the highest mean balanced accuracy ($87.17\% \pm 0.24\%$), significantly outperforming a fully connected deep neural network (FNN: $81.58\%$) and Random Forest ($80.97\%$). Linear models (LDA: $57.21\%$; SVM: $51.01\%$) performed poorly, indicating that DFA-derived criticality features reside on a distinct, non-linear manifold. Probabilistic decoding of EEG criticality provides a high-accuracy sensing mechanism for pBCIs. This robust classification pipeline supports the development of state-dependent neurofeedback, such as targeted auditory stimulation, to enhance cognitive recovery.

06.
medRxiv (Medicine) 2026-06-18

Comparative Evaluation of Pretrained Large Language Models for Suicide Risk Prediction from Clinical Notes in U.S. Veterans

Background: Suicide remains a significant and potentially preventable cause of death among United States veterans. Predictive models based on structured electronic health record (EHR) data, including the U.S. Department of Veterans Affairs' Recovery Engagement and Coordination for Health-Veterans Enhanced Treatment (REACH-VET) program, aim to identify individuals at elevated risk for enhanced monitoring and follow-up. Increasing evidence suggests that unstructured clinical narratives contain additional psychosocial information that may enhance risk prediction when analyzed using natural language processing (NLP). However, optimal approaches for representing clinical text remain uncertain. Recent advances in large language models (LLMs) enable contextual text representations that capture complex semantic relationships beyond traditional lexical methods. Methods: We compared the predictive performance of pretrained LLMs with classical bag-of-words (BoW) representations for suicide risk prediction using clinical notes from 27,241 veterans receiving care in the Veterans Health Administration. Patients were stratified by REACH-VET risk tier (low, moderate, high), and models were evaluated across prediction windows defined by note look-back periods (

07.
arXiv (CS.LG) 2026-06-18

Hierarchical Planning with Latent World Models

arXiv:2604.03208v2 Announce Type: replace Abstract: World models are a promising path to zero-shot embodied control through planning. However, existing world model planners struggle on long-horizon, multi-stage tasks: prediction errors compound and naive search is exponential in the planning horizon. Hierarchy mitigates both by decomposing tasks into shorter, tractable subproblems; yet prior hierarchical approaches either amortize control into task-specific policies (hierarchical RL) or assume low-dimensional states and known dynamics (classical hierarchical MPC). We present Hierarchical Planning with Latent World Models (HWM), an architecture and planning paradigm for hierarchical model predictive control (MPC) directly on visual world models trained solely via next-latent prediction. HWM learns world models at multiple temporal scales within a shared latent space, so predictions from the long-horizon model serve as subgoals for the short-horizon model via latent matching, without task-specific rewards, skill learning, or hierarchical policies. To keep long-horizon search tractable, HWM learns an action encoder that compresses primitive action chunks into latent macro-actions. On real-world Franka manipulation, HWM solves pick-and-place from a single goal image at 70% success vs. 0% for single-level planning. Across simulated push manipulation and maze navigation, HWM consistently improves performance on long-horizon tasks while requiring up to 3x less planning compute.

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

Efficient Neural Network Model Selection for Few-Class Application Datasets

arXiv:2606.19712v1 Announce Type: new Abstract: While much effort has focused on developing and benchmarking high-performance neural networks, less attention has been given to how dataset properties, known to practitioners, can guide efficient model selection. Neural models are typically evaluated on datasets with thousands of classes, yet many real-world applications involve fewer than ten. To address this understudied but common setting, we develop a measure of classification difficulty based on data-side properties and show how it enables more efficient model selection for few-class datasets, where traditional approaches are less effective. We term this phenomenon "few-class distinctiveness". Our metric allows comparison of models and datasets 6 to 29$\times$ faster than repeated training and testing. Leveraging this insight, we extend scaled model families below the smallest published models, achieving greater efficiency at similar accuracy, for example models up to 42% smaller than YOLOv5-nano for a mobile robot task. Targeting resource-constrained applications, we demonstrate few-class model selection across mobile robot, drone, and IoT scenarios, highlighting practical gains in efficiency without sacrificing performance.

09.
bioRxiv (Bioinfo) 2026-06-11

A high-quality chromosome-scale reference genome assembly for Asparagus racemosus var. CIM-Shakti (Shatavari), a medicinal plant of Ayurvedic importance

Asparagus racemosus Wild., commonly known as Shatavari, is an important medicinal plant in Ayurveda and is valued for its steroidal saponins, particularly shatavarin compounds, which contribute to its adaptogenic, galactagogue, immunomodulatory, and therapeutic properties. Despite its medicinal and economic importance, genomic resources for this species have remained limited, restricting molecular breeding, pathway discovery, and comparative evolutionary studies within Asparagaceae. Here, we report a high quality chromosome scale reference genome assembly of A. racemosus var. CIM Shakti generated using PacBio HiFi long read sequencing and Omni C chromatin conformation scaffolding. The pseudo haploid assembly spans 817 Mb across 53 scaffolds, with a scaffold N50 of 98.50 Mb, L50 of 5, and a largest scaffold of 113.80 Mb. Ten major chromosome scale pseudomolecules were resolved, corresponding to the haploid chromosome complement of A. racemosus. The assembly showed high gene space completeness, with BUSCO completeness of 99.8% against the Eukaryota dataset and 98.0% against the Embryophyta dataset. BlobToolKit profiling further supported assembly quality, with GC content of approximately 39 to 40% and no major evidence of contamination. EDTA based repeat annotation identified 580.93 Mb of interspersed repetitive elements, accounting for 71.06% of the 817.57 Mb genome assembly. The repeat landscape was dominated by LTR retrotransposons, particularly Gypsy elements, which accounted for 25.01% of the assembly, followed by unclassified LTR elements at 26.58% and Copia elements at 4.84%. Structural and functional annotation identified 29,199 protein coding genes represented by 29,199 transcript models, 138,433 exons, and 125,201 CDS features. The annotation was structurally robust, with an average gene length of 4,605.1 bp, 4.74 exons per transcript, and 97.80% of transcripts containing multiple exons. The CIM Shakti reference genome provides a foundational genomic resource for investigating steroidal saponin biosynthesis, sex chromosome evolution, repeat driven genome expansion, and comparative genomics in Asparagaceae. This assembly will support future studies on medicinal trait improvement, conservation genomics, and genomics assisted breeding of climate resilient Shatavari cultivars.

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

Environment-Grounded Automated Prompt Optimization for LLM Game Agents

LLM agents in interactive environments are highly sensitive to their prompts, yet prompt engineering remains a manual, task-specific process. We introduce an automated prompt optimization framework for LLM agents that decomposes the observation-to-action pipeline into a goal-conditioned descriptor agent and an action selection agent, and iteratively refines each module's prompt through an LLM-driven evolutionary loop guided by environment returns. We propose a behavior analyzer to attribute episode outcomes to specific prompt components, and a mutator to propose targeted revisions to the prompt, before validating them through environment rollouts. We evaluate on all five BabyAI tasks in the BALROG benchmark, comparing our pipeline against BALROG's RobustCoTAgent under both plain and guided prompt initializations. Optimization improves performance consistently across tasks and conditions, without requiring updates to the model weights. On PutNext, a multi-step coordination task where the RobustCoTAgent achieves 0% success, our framework reaches up to 72.5% success rate using the same underlying LLM with optimized prompts. These results suggest that a multi-agent framework, combined with automatic prompt optimization, enhances LLMs without the need for fine-tuning or extensive human supervision.

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

Cross-Modal Benchmarking for Robotic Perception in Natural Environments

Natural environments present a complex challenge to robotics perception systems. Current models, particularly vision foundation models, are largely trained on structured, urban environments leading to weaknesses in their perception for field robotics tasks. We showcase the limitations of current models using our recently released WildCross benchmark, a new cross-modal benchmark for place recognition and metric depth estimation in large-scale natural environments. WildCross comprises over 476K sequential RGB frames with semi-dense depth and surface normal annotations, each aligned with accurate 6DoF pose and synchronized dense lidar submaps. In this work, we provide an expanded analysis of the benchmark results from the recent WildCross benchmark, with particular emphasis on expanded metric depth estimation experiments. Access to the code repository and dataset for this work can be found at https://csiro-robotics.github.io/WildCross.

12.
arXiv (CS.AI) 2026-06-19

AAPA: Adversarially Anchored Preference Alignment for Post-Training of Large Language Models

arXiv:2509.25148v2 Announce Type: replace Abstract: Post-training alignment of large language models often combines supervised fine-tuning (SFT) on expert demonstrations with reinforcement learning (RL) from preference or verifiable feedback. SFT provides a useful behavioral anchor but can overfit to static demonstrations, whereas RL encourages exploration but may drift from expert behavior or exploit imperfect rewards. We propose AAPA (Adversarially Anchored Preference Alignment), a plug-in framework that augments existing post-training objectives with a sentence-level adversarial anchoring signal. AAPA compares policy rollouts with offline, pre-collected expert responses using a fixed lightweight discriminator, and therefore requires neither online teacher inference nor discriminator co-training during policy optimization. The same anchoring term can be added to SFT, GRPO, and CHORD while preserving their original training pipelines. Experiments on instruction-following benchmarks show that AAPA consistently improves the corresponding base objectives across model scales. In particular, the staged AAPA configuration improves over a strong GRPO baseline by 5.77\% on \texttt{Qwen3-0.6B} and 3.75\% on \texttt{Qwen3-4B}. Further analyses on response length, log-probability distributions, and discriminator variants suggest that adversarial anchoring provides a stable semantic grounding signal for preference optimization. Code is available at \url{https://github.com/IsFaqq/AAPA}.

13.
arXiv (CS.CV) 2026-06-15

Trimodal Glioma Representation Alignment via Volumetric Contrastive Learning

Glioma grading and survival prediction require the integration of heterogeneous information collected at different spatial and biological scales. Histopathology describes tissue morphology, mRNA expression captures molecular activity, and magnetic resonance imaging provides a non-invasive view of tumor extent and radiological heterogeneity. Existing glioma prognosis models often combine only two of these sources, while their alignment objectives remain mostly pairwise. This paper introduces GLORIA, a novel trimodal framework for GLioma Omics - Radiology - hIstopathology Alignment. GLORIA processes whole-slide image regions, gene-expression profiles, and 3D MRI volumes through modality-specific encoders, projects them into a shared latent space, and aligns them with a Gramian contrastive loss that measures the volume spanned by the three modality embeddings. The aligned representations are fused through a cross-modal gating module and optimized jointly for three-class glioma grading and overall survival prediction. We evaluate GLORIA on a matched TCGA-GBM/LGG and BraTS21 cohort, comprising 132 patients with all three modalities. On the shared trimodal test set, GLORIA improves over the bimodal WSI-mRNA baseline in all the metrics considered.

14.
arXiv (quant-ph) 2026-06-19

Quantum Kernels are Spectral Tensor Networks

arXiv:2606.20402v1 Announce Type: new Abstract: Quantum kernels admit Fourier representations whose frequencies are determined by the data-encoding gates of the underlying feature map. We show that entangling tensor kernels are matrix product operator factorizations of the corresponding Fourier coefficient tensors, thereby identifying quantum kernels as spectral tensor networks. By grouping gate-level frequency configurations that yield the same feature-wise frequency, we obtain a grouped Fourier form that induces a more compact spectral tensor network representation of the kernel. We further show that kernel target alignment serves as a bridge between the Fourier and tensor network views. On a grid that resolves the accessible Fourier modes, it becomes the Frobenius cosine similarity between Fourier coefficient tensors. Our numerical experiments show that layered quantum kernels admit accurate representations with small bond dimension, revealing a compressibility governed by correlations between Fourier modes. This compressibility provides a diagnostic of classical representability and of whether kernel evaluation is likely to remain classically tractable.

15.
PLOS Computational Biology 2026-06-02

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

作者:

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.

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

Z-Plane Neural Networks: Bounded Geometric Activation Replaces ReLU and LayerNorm

arXiv:2606.15669v1 Announce Type: cross Abstract: Modern deep neural networks rely on Euclidean scalar activations (e.g., ReLU) and global normalization techniques (e.g., LayerNorm) to prevent gradient instability in deep architectures. However, these mechanisms inherently cause dead neurons, discard critical directional information, and destroy the orthogonality of feature representations. Inspired by the frequency-modulation transmission of biological axons, we propose the Z-Plane Neural Network, which maps hidden states into 2D phasor bundles on a hypersphere. We introduce a novel geometric activation function, Radial Bounding($\mathbf{x} / \max(1, \|\mathbf{x}\|_2)$), which limits the energy magnitude while preserving the phase (direction). We demonstrate mathematically that this isotropic activation maintains 1-Lipschitz continuity and prevents gradient vanishing by preserving tangential gradients. Empirically, a 100-layer Z-Plane Multi-Layer Perceptron (MLP)-entirely devoid of ReLU and LayerNorm-successfully converges on the MNIST dataset with 98.34% accuracy and absolute numerical stability, proving that bounded geometric activation alone is sufficient for stable deep learning.

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

Wavelength-Multiplexed 2D Beam Steering via a Passive Diffractive Network

We introduce a wavelength-addressable diffractive optical network that transforms illumination wavelength into a high-dimensional control parameter for arbitrarily programmable 2D beam steering. The proposed passive architecture comprises cascaded spatially optimized diffractive layers, jointly designed using deep learning, to rapidly map distinct wavelengths to predefined/desired output angles. Unlike conventional single-layer dispersive optical elements, which are physically restricted to 1D linear mapping, this framework harnesses complex wavefront transformations to utilize the illumination wavelength as an intrinsic addressing key for arbitrary 2D beam steering, eliminating the need for mechanical scanning or electronic phase control. We numerically demonstrate wavelength-controlled beam steering across 625 wavelength channels spanning 400-750 nm, realizing a 25 x 25 array of independently addressable beam positions with subwavelength positioning accuracy and high channel fidelity. Unlike conventional gratings, which constrain wavelength routing to a linear trajectory, the proposed diffractive network performs nonlocal wavefront transformations, enabling arbitrary wavelength-to-angle mappings across a 2D field of view. We further validate the proposed framework experimentally in both the terahertz and visible spectral regimes, demonstrating wavelength-multiplexed beam steering using 3D fabricated passive diffractive layers at terahertz frequencies and phase-only spatial light modulators in the visible spectrum. This wavelength-addressable diffractive architecture establishes a compact and scalable paradigm for high-speed programmable beam steering, with potential applications in optical communications, routing, imaging, sensing, and emerging photonic information-processing systems.

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

Optimizing Health Coverage in Ethiopia: A Learning-augmented Approach and Persistent Proportionality Under an Online Budget

arXiv:2509.00135v2 Announce Type: replace Abstract: As part of nationwide efforts aligned with the United Nations' Sustainable Development Goal 3 on Universal Health Coverage, Ethiopia's Ministry of Health is strengthening health posts to expand access to essential healthcare services. However, only a fraction of this health system strengthening effort can be implemented each year due to limited budgets and other competing priorities, thus the need for an optimization framework to guide prioritization across the regions of Ethiopia. In this paper, we develop a tool, Health Access Resource Planner (HARP), based on a principled decision-support optimization framework for sequential facility planning that aims to maximize population coverage under budget uncertainty while satisfying region-specific proportionality targets at every time step. We then propose two algorithms: (i) a learning-augmented approach that improves upon expert recommendations at any single-step; and (ii) a greedy algorithm for multi-step planning, both with strong worst-case approximation estimation. In collaboration with the Ethiopian Public Health Institute and Ministry of Health, we demonstrated the empirical efficacy of our method on three regions across various planning scenarios.

19.
arXiv (CS.LG) 2026-06-12

Optical Implementation of Equilibrium Propagation Using Spatial Photonic Ising Machines

arXiv:2606.13454v1 Announce Type: cross Abstract: Equilibrium Propagation offers a compelling alternative to traditional machine learning for training energy-based networks. Here we demonstrate a hybrid optical-digital implementation of EP using a Spatial Photonic Ising Machine (SPIM). The SPIM exploits the gauge transformation method to optically encode both continuous neuron states and rank-1 binary trainable patterns as phase modulations via a spatial light modulator, with inference realized using a finite difference scheme. The experimental system is evaluated on the Wine classification dataset. The potential of this approach, including the use of continuous couplings and structured coupling matrices, is evaluated numerically on the more complex MNIST dataset. Our work provides a concrete pathway toward energy-efficient physical implementations of Equilibrium Propagation.

20.
arXiv (CS.AI) 2026-06-16

Model-Native Computing Architecture: Envisioning Future System Architecture Through the Lens of Computer Architecture

arXiv:2606.00288v2 Announce Type: replace Abstract: Large language models are undergoing a transition from model technology to system technology. Engineering challenges like cache reuse, context capacity, agent scheduling, and permission control resemble classical computer systems problems. This raises a question: if we treat the LLM as a CPU, KV cache as processor cache, context window as main memory, and agent framework as an operating system, can decades of computer architecture wisdom guide next generation model native systems? This paper pursues this analogy as a visionary survey. We map computer architecture concepts onto the emerging model native stack, survey literature across LLM as OS, memory management, agent frameworks, tool protocols, multi agent coordination, cognitive architectures, and safety governance, finding that each addresses a different layer without a unifying model. We propose the Intelligent Computing Architecture (ICA): six functional layers with interface contracts and design axioms. We resolve the tension over whether the LLM resembles a CPU or OS via a dual plane architecture a probabilistic execution plane (what can be computed) and a deterministic control plane (what should be computed), with every layer passing through as a graded crossover. We propose three Amdahl style design heuristics Semantic Locality, Context Budget, and Agent Speedup as organizing back of envelope models, illustrate their parameter ranges with published data, and identify predictive validation as the principal open task. We articulate analogy boundaries, note differences between silicon and model era architectures, and propose a research roadmap. This is a conceptual and survey contribution with no new experimental results.

21.
medRxiv (Medicine) 2026-06-17

Characterizing the genetic basis of Cardio-Renal-Metabolic multimorbidity using multivariate genomic modelling

Cardio-renal-metabolic multimorbidity (CRMM) encompasses interrelated conditions affecting the heart, kidneys, and metabolic systems. Although the genetics of individual components are well studied, their shared architecture remains unclear. Here, we performed the largest multi-ancestry multivariate GWAS of CRMM across seven biobanks, including individuals of European (EUR; neff = 353,130), African (AFR; neff = 75,436), and East Asian (EAS; neff = 164,373) ancestry. We identified 287 lead loci in EUR, 30 in AFR, and 202 in EAS. Cross-ancestry analyses revealed ancestry-specific signals and 24 shared loci mapping to FTO and TCF7L2. Drug-repurposing highlighted candidates used for type 2 diabetes and hypertension. Mendelian randomization supported causal links with diverse diseases, while polygenic risk scores showed improved prediction across ancestries. Collectively, these findings advance understanding of CRMM genetics and inform precision medicine.

22.
arXiv (CS.AI) 2026-06-16

Cordyceps: Covert Control Attacks on LLMs via Data Poisoning

arXiv:2605.26595v2 Announce Type: replace-cross Abstract: Large language models (LLMs) are often fine-tuned on uncurated text datasets that adversaries can poison. Existing poisoning attacks primarily rely on fixed trigger phrases that defenses such as outlier detection, clean-data regularization, or online monitoring can neutralize. In this paper, we propose a data poisoning method that teaches an LLM an information hiding scheme reliably and stealthily through semantic associations between shared knowledge such as facts or concepts and attacker-chosen phrases. The induced hiding scheme can encode and decode arbitrary malicious instructions, thus revealing a new and subtle poisoning-induced vulnerability: covert control attacks. We precisely characterize covert control attacks and evaluate them across $5$ LLMs, $3$ backdoor defenses, and $4$ prompt injection defenses. With a small poisoned fraction, covert control attacks outperform heuristic-based prompt injection attacks in average attack success rate by about $40\%$ relative to clean fine-tuned models. They also circumvent defenses based on detection and fine-tuning, maintaining up to $93\%$ attack success rate after backdoor defenses and up to $98\%$ after prompt injection defenses.

23.
arXiv (quant-ph) 2026-06-11

Dynamically Optimal Unraveling Schemes for Simulating Lindblad Equations

arXiv:2509.19887v2 Announce Type: replace Abstract: Stochastic unraveling schemes are powerful computational tools for simulating Lindblad equations, offering significant reductions in memory requirements. However, this advantage is accompanied by increased stochastic uncertainty, and the question of optimal unraveling remains open. In this work, we investigate unraveling schemes driven by Brownian motion or Poisson processes and present a comprehensive parametric characterization of these approaches. For the case of a single Lindblad operator and one noise term, this parametric family provides a complete description for unraveling scheme with pathwise norm-preservation. We further analytically derive dynamically optimal quantum state diffusion (DO-QSD) and dynamically optimal quantum jump process (DO-QJP) that minimize the growth rate of the variance of an observable locally in time. Compared to jump process ansatz, DO-QSD offers two notable advantages: firstly, the variance for DO-QSD can be rigorously shown not to exceed that of any jump-process ansatz locally in time; secondly, it has very simple expressions. Numerical results demonstrate that the proposed DO-QSD scheme may achieve substantial reductions in the variance of observables and the resulting simulation error.

24.
bioRxiv (Bioinfo) 2026-06-18

Predicting optimal growth temperatures of bacteria using learned structural information from a single protein

Temperature is a fundamental determinant of bacterial physiology and ecology. Optimal growth temperature (OGT) is highly variable across species, contributing to differences in where and when species are most likely to thrive. Although the OGTs for most bacteria remain unknown, the increasing availability of genomes from uncultivated and cultivated taxa has made it advantageous to build genomic, cultivation-independent models to infer OGT. However, pre-existing genomic models often lack the generalizability and mechanistic grounding required for robust inferences of OGT. We propose a novel framework for predicting bacterial OGT which uses learned protein structural signatures of thermal adaptation. We hypothesize that biophysical tradeoffs which dictate enzymatic functions across variable temperatures provide a more robust empirical basis for OGT prediction than broad genomic features. Our OGT-predicting model, ROSEATE, is based on a single gene, adenylate kinase (ADK), that encodes for a ubiquitous enzyme essential for energy homeostasis. ROSEATE uses high-dimensional latent space encoding via MSA Transformer, a protein language model which embeds ADKs in a manner which preserves biophysical information about embedded proteins. We show that the accuracy of the ROSEATE model is on par with other genome-based models, has a high degree of phylogenetic generalizability, and the ESM embeddings effectively capture key temperature-adaptive enzyme characteristics derived from AlphaFold structures. Because ROSEATE is based on analyses of a single ubiquitous protein, it can be used with metagenomic data to infer the community-level variation in bacterial OGTs. We demonstrate this feature of ROSEATE by reconstructing ADK sequences from over 500 environmental and host-associated metagenomes, successfully distinguishing community-wide thermal preferences across diverse habitats, from polar oceans to mammalian guts. By transitioning from genomic proxies to informationally dense protein structural features, this work provides an efficient, interpretable tool for predicting bacterial OGTs across taxa and whole communities.

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

scGTN: Deep Siamese Graph Transformer Network for Single-cell RNA Sequencing Clustering

arXiv:2606.18672v1 Announce Type: cross Abstract: Single-cell RNA sequencing (scRNA-seq) serves a pivotal role in characterizing gene expression at the cellular level, enabling the identification of cell types and advancing the understanding of cellular heterogeneity. Despite the significant progress in scRNA-seq data clustering, we argue that current methods always ignore the sparsity and noise, as well as the complex intercellular structural information inherent in scRNA-seq data. Toward this end, in this paper, we propose a novel single-cell RNA-seq clustering framework via deep Siamese Graph Transformer Network (termed scGTN), which explicitly integrates gene expression profile and intercellular structural dependencies for cell clustering. In particular, we formulate scRNA-seq data as a graph and construct two augmented graph views that serve as dual views to capture complementary intercellular information. Then, a Siamese graph transformer network is employed to explicitly incorporate shortest-path information and node-wise distances for capturing richer structural relationships between cells. Finally, we employ an optimal transport strategy to guide the cell clustering in a self-supervised manner. Extensive experiments on multiple benchmark scRNA-seq datasets demonstrate that our scGTN consistently outperforms existing methods. Our code is available at https://github.com/W-RMSL/scGTN.