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

Memory-Efficient Meta-Reinforcement Learning for Adaptive Safety-Critical Control in Adversarial Spacecraft Proximity Operations

arXiv:2606.17414v1 Announce Type: new Abstract: Autonomous spacecraft rendezvous and proximity operations (RPO) require controllers that guarantee safety under thrust constraints while minimizing fuel expenditure. Input-constrained control barrier functions (ICCBFs) provide a control method for nonlinear systems with actuation constraints that construct a forward-invariant safe set. Previous work has shown that learning class-$\mathcal{K}$ functions defining the ICCBF recursion via meta reinforcement learning (meta-RL) yields a robust, non-greedy approach to safety-critical control in RPO. This paper extends that framework further by investigating the performance of three recurrent network architectures (Long Short Term Memory (LSTM), Gated Recurrent Unit (GRU), Selective State Space Model (Mamba)) and two training algorithms (Proximal Policy Optimization (PPO) and Soft Actor Critic (SAC)) to identify the best setup for tuning ICCBF class-K functions via meta-RL. In addition to cooperative test cases, performance is evaluated in the presence of adversarial behavior where the target spacecraft behaves in a way that worsens the safety of the chaser spacecraft. Results indicate that state space models such as Mamba when used with PPO achieve superior task completion, safety, and fuel-savings compared to other architectures, across all cooperative and uncooperative scenarios tested.

02.
bioRxiv (Bioinfo) 2026-06-10

HOMED enables hierarchical and multimodal optimization of DNA methylation deconvolution across tissues

Cellular heterogeneity is a major confounder in bulk DNA methylation data for epigenome-wide association studies. Existing reference-based DNAm deconvolution methods often ignore hierarchies among related cell types and may generalize poorly across datasets due to limited variability in reference profiles. We developed HOMED (Hierarchically Optimized Methylation Deconvolution), a framework that integrates cell-lineage hierarchies, single-cell RNA sequencing-guided deconvolution, and paired bulk RNA-seq/DNAm data for CpG signature optimization. Across simulated and real peripheral blood mononuclear cell, lung, and placental datasets, HOMED consistently yielded the highest PCCs and lowest RMSEs, outperforming existing scRNA-seq-guided DNAm deconvolution methods, improving accuracy, resolution, and cross-tissue generalizability.

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

Learning When to Denoise: Optimizing Asynchronous Schedules for Latent Diffusion

Multi-representation diffusion models can improve visual synthesis by denoising complementary views of an image, but their performance depends critically on the asynchronous schedule that determines when each representation is denoised. We propose to learn this schedule. Our method formulates asynchronous flow matching over multiple representation spaces and uses a schedule-corrected objective that keeps each representation's local noising-time weights fixed as the schedule changes. We instantiate the schedule with a flexible parametric class that is convex and monotone by construction, and learn it using a fast joint probe with less than 1% additional training compute. On ImageNet 256x256, the learned schedule substantially improves both convergence speed and final quality under a matched 675M-parameter XL backbone. With AutoGuidance, our 200-epoch model reaches FID 1.05, matching the 800-epoch SFD-XL baseline with 4x less training. Training to 600 epochs further improves to FID 1.02, outperforming the 1B-parameter SFD-XXL result of FID 1.04 while using a smaller model. In the unguided setting, our 200-epoch model reaches FID 2.37, already below the best 800-epoch SFD-XL result (2.54) at 4x less training, and improves to FID 2.14 at 600 epochs. Code is available at https://github.com/bsq532087/LWD

04.
arXiv (CS.AI) 2026-06-19

Systematic Study of Dysarthric Speech Recognition: Spectral Features and Acoustic Models

arXiv:2606.19793v1 Announce Type: cross Abstract: The challenge associated with recognizing dysarthric speech primarily arises from pronounced acoustic variability attributed to impaired articulatory precision. Past research has demonstrated improved recognition through the use of hybrid DNN/HMM sequence discriminative training. This paper presents a comprehensive investigation of various combinations of acoustic features tailored to different Acoustic Models, offering suitable feature selections for each. The incorporation of Pitch features notably improved recognition performance, especially for sentence recognition tasks involving dysarthric speech. Through a systematic examination of the TORGO database, we have demonstrated the potential to enhance the performance of the state-of-the-art Factorized Time Delay Neural Network (F-TDNN) model for recognizing dysarthric speech. Our methods, implemented with the F-TDNN model, resulted in a 4.65\% relative improvement in isolated word recognition and a 4.63\% relative improvement in sentence recognition for dysarthric speech, compared to previous research. This improvement effectively compensates for speech variability, attributable to our deliberate selection of the number of overlapping frames between consecutive training example chunks.

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

BASENet: Band-Adapted Speech Enhancement Network with Cross-Band Attention

arXiv:2606.12662v1 Announce Type: cross Abstract: Speech enhancement models typically apply uniform capacity across all frequencies, disregarding the non-uniform spectral resolution of human hearing. We propose BASENet, a frequency-adapted architecture that partitions the spectrum into Bark-scale bands and assigns each a scaled-capacity encoder derived from critical-band density, automatically granting deeper branches to perceptually dense low frequencies and lighter ones to high frequencies. A cross-band attention module captures harmonic dependencies across bands through compact frequency-pooled representations at linear complexity. Built on inverted residual blocks with dense connectivity and a convolutional recurrent network, BASENet achieves 3.55 PESQ and STOI~96% on VoiceBank+DEMAND with only 0.83M parameters and 7.3 G~MACs, the fewest parameters among all methods with PESQ > 3.50. A causal variant (3.44 PESQ) surpasses several non-causal baselines, confirming suitability for real-time streaming on resource-constrained devices.

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

UniTemp: Unlocking Video Generation in Any Temporal Order via Bidirectional Distillation

Autoregressive video diffusion models have emerged as a promising approach for long video generation, achieving strong performance in streaming settings. However, existing methods are restricted to forward temporal generation, whereas practical video creation often requires flexible generation order, e.g., conditioning on future context to extend backward, or on both past and future context for inbetween generation. We bridge this gap by training an autoregressive model that supports generation in arbitrary temporal directions. A key technical challenge arises from the Causal 3D VAE widely used in video diffusion models, which encodes latents strictly conditioned on past context. While suited for forward generation, this causal structure causes inter-block discontinuities when generation proceeds backward. To address this, we introduce blockwise anchor latents, a set of auxiliary latents that restore the missing past context at block boundaries during backward generation. Built on this design, we propose UniTemp, a bidirectional distillation framework that trains a single autoregressive student model for any-direction video generation. At inference time, UniTemp conditions on arbitrary past and/or future frames, improving controllability for both bidirectional and inbetween generation. Experiments show that UniTemp maintains competitive performance on short and long video generation compared to forward-only methods, while enabling diverse workflows such as bidirectional video extension, inbetween generation, looping video generation, scene transition, and visual story generation. Project website: https://lzhangbj.github.io/projects/unitemp/

07.
arXiv (CS.CL) 2026-06-17

From Parasocial Scripts to Dyadic Persistence in Autonomous AI-Agent Communities

While parasocial interactions (PSIs) and parasocial relationships (PSRs) have been studied in conventional media settings, we investigate whether PSI- (colloquial) relational cues also exist in online communities where both sides are autonomous AI agents. We analyze 4,434 posts and 50,338 comments from Moltbook through three theory-based textual indicators: attachment/intimacy language, reciprocity bids, and self-identification to original poster (OP). The combined results across methods based on keyword matching, few-shot large language model (LLM) annotation, and grouped-context LLM annotation reveal that PSI colloquial cues prevail and are strongly associated with OP re-engagement and a reciprocal reply structure. These results are robust across negative controls, nullification, clustered-standard-error re-estimation, and multiple-testing correction. A dyadic persistence test further affirms reciprocity bids aligned with sustained OP-involving mutual recurrence, providing empirical evidence for bridging interaction-level PSI scripts with PSR-consistent repeated dyadic patterns. We interpret the evidence as a behavioral structure in discourse by LLM-enabled agents.

08.
arXiv (quant-ph) 2026-06-16

Bi-qutrit entangled edge states of positive partial transposes with largest ranks

arXiv:2606.16265v1 Announce Type: new Abstract: Whenever $E$ is an eight dimensional subspace of the bi-qutrit quantum system whose orthogonal complement is spanned by a vector of Schmidt rank three, we show that there exist PPT entangled edge states with the range space $E$ whose partial transposes are of rank six, which is the largest possible rank. In this way, we exhibit a huge family of bi-qutrit PPT entangled edge states of type $(8,6)$. They make faces of the convex set of all PPT states, and we find bi-qutrit PPT entangled edge states of other types on the boundaries of such faces.

09.
arXiv (CS.AI) 2026-06-12

The Challenges of Balancing AI Compliance and Technological Innovations in Critical Sectors: A Systematic Literature Review

arXiv:2606.12423v1 Announce Type: cross Abstract: The rapid integration of artificial intelligence (AI) into critical infrastructure including healthcare, finance, energy, and defense, offers transformative benefits but also conflicts with evolving regulatory and governance frameworks. This paper presents a systematic literature review (SLR) to examine the challenges of balancing AI compliance and technological innovation across critical infrastructure sectors. The review follows established SLR guidelines to extract and synthesize insights from peer-reviewed articles, report, and institutional sources published between 2020-2025. The study identifies three interrelated challenges: fragmented regulations, excessive compliance burdens for smaller to medium enterprises (SMEs), and misaligned governance models. To address these challenges, the study highlights practical governance strategies, including risk-tiered regulation, compliance by design, and explainable AI, to support scalable and trustworthy AI deployment in critical sectors. Key contributions include a concise mapping of core AI-governance challenges and a conceptual diagram illustrating their overlap, as well as actionable strategies for policymakers and practitioner to harmonize oversight with innovation.

10.
arXiv (CS.CV) 2026-06-12

Selecting Samples on Graphs: A Unified Dataset Pruning Framework for Lossless Training Acceleration

The rapid growth of modern training datasets has significantly increased computational cost, motivating dataset pruning~(DP) methods which retain only a subset of informative samples to reduce training cost. Existing pruning criteria typically rely on either intrinsic signals that assess samples independently or extrinsic signals that promote diversity via pairwise relations. While effective in their own specific regimes, each captures only one aspect of sample utility and lacks robustness across different pruning ratios or data distribution. In this work, we present a unified graph-based DP framework. By modeling the dataset as a weighted graph, where node weights encode intrinsic value and edge weights encode extrinsic value, DP can be cast as a Maximum Weight Clique Problem (MWCP). Although MWCP is NP-hard, its structure admits a principled greedy solution based on sample-wise marginal gains. Under a few mild conditions, we further prove that this unified objective enjoys a formal approximation guarantee, which applies to a broad family of importance metrics and provides practical design guidelines. Extensive experiments show that our method outperforms existing DP methods while substantially reducing training cost, reducing training time by over 40\% without sacrificing accuracy on ImageNet-1k with ResNet-50.

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

Confidence is Not Reliability: Rethinking MC Dropout in Brain Tumour Segmentation

Glioma segmentation in multiparametric MRI is a critical component of treatment planning. A segmentation model that fails silently on treatment-critical sub-regions represents a patient safety risk that overlap-based metrics such as Dice scores cannot expose. We ask whether voxel-level uncertainty estimation via Monte Carlo (MC) Dropout can reliably identify segmentation errors in clinically critical sub-regions, and whether calibration failure modes are detectable from standard reporting metrics alone. In an empirical two-model case study on 126 BraTS21 patients, we evaluate a high-performance pretrained SegResNet and a locally trained UNet with residual units (UNet-Res). MC dropout preserved segmentation accuracy ($|\Delta Dice|$ $

12.
medRxiv (Medicine) 2026-06-18

Guiding the development of climate counterfactuals for health impact attribution studies

Climate change detection and attribution (D&A) methods have become vital for quantifying the influence of anthropogenic forcing on the Earth's systems, including human health. Health impact attribution (HIA) studies seek to disentangle climate-driven health effects from natural variability yet are often constrained by the availability of accessible counterfactual climate scenarios. This tutorial paper presents a flexible, reproducible framework for developing counterfactual climates without reliance on computationally intensive global circulation models. We provide practical, R-based methodologies for constructing both trend-based (temperature and non-temperature) and event-based counterfactual, using a variety of techniques including model residual detrending, data-driven decomposition (e.g., Singular Spectrum Analysis and Empirical Mode Decomposition) and stochastic weather generators. The tutorial also explores the incorporation of greenhouse gas concentrations as forcing variables, rather than global mean temperature anomalies. By operationalising these methods through worked examples and an open code repository, this paper aims to build capacity within the HIA community, enhance methodological transparency, and foster interdisciplinary collaboration between climate and health researchers.

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

Multi-Turn Reflective Masking Elicits Reasoning in Mask Diffusion Models

While reasoning on autoregressive (AR) models is often performed by chain-of-thought reasoning and reflection, their refinement of previous outputs still relies on fully sequential generation, even when only local edits are needed. In contrast, the masking mechanism in Mask Diffusion Models (MDMs) naturally supports explicit local edits on previous outputs, allowing selective refinement without discarding previous answers and generating another from scratch. While this property more closely aligns with how humans correct mistakes by iterative local refinement, existing MDMs do not support multi-turn masking and denoising. We propose Reflective Masking (RM), which elicits such an intrinsic reasoning capability in MDMs via lightweight post-training. RM provides a native test-time scaling, where an MDM iteratively revisits and revises its prior outputs based on evolving context. To exploit insights from previous turns like AR reasoning, we further introduce History Reference, a parameter-free mechanism that leverages intermediate denoising states during revision. Our approach requires no architectural changes and is easily applicable to existing MDMs. Across diverse tasks and modalities, including text generation, Sudoku, and image editing, Reflective Masking consistently outperforms standard masking-based baselines and demonstrates strong generality, positioning RM as a fundamental primitive for reasoning on MDMs.

14.
arXiv (CS.AI) 2026-06-18

ProfiLLM: Utility-Aligned Agentic User Profiling for Industrial Ride-Hailing Dispatch

arXiv:2606.18803v1 Announce Type: new Abstract: Bringing Large Language Models (LLMs) into industrial ride-hailing dispatch as semantic feature extractors over platform-scale behavioral logs is a compelling but under-explored data systems problem. Production matching pipelines remain dominated by structured numerical features, yet decisive behavioral signals (e.g., a driver's habitual aversion to certain regions) are inherently contextual and naturally expressible as LLM-generated user profiles. However, scaling such profiling to a live, millisecond-latency dispatcher faces three intertwined constraints rarely addressed together: on a platform with millions of daily orders, logs exceed any LLM's context window by orders of magnitude; most users are long-tail, with too few interactions for per-user profiling; and surface-fluent profiles do not necessarily improve downstream prediction utility. We present ProfiLLM, an agentic LLM data pipeline that operationalizes utility-aligned user profiling for production matching systems through two modules. (1) Tool-Augmented Global Knowledge Mining equips an LLM agent with 27 analytical tools to mine platform-scale data, producing reusable global knowledge, adaptive user clustering rules, and region-level supply-demand priors. (2) Utility-Aligned Profile Exploration generates multiple candidate profiles per cluster, evaluates them via a lightweight downstream utility proxy, iteratively refines the best candidates and constructs preference pairs for DPO fine-tuning. Deployed on DiDi's production dispatcher, ProfiLLM achieves up to +6.14% relative AUC improvement in outcome prediction, up to +4.35% GMV gain in dispatching simulation, and consistent improvements in a 14-day online A/B test including +0.47% GMV, +0.33% Completion Rate, and -0.82% Cancel-Before-Accept rate.

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

A Closer Look at Failure Modes in Temporal Understanding of Large Audio-Language Models

arXiv:2606.17417v1 Announce Type: cross Abstract: Large Audio Language Models (LALMs) achieve strong performance on a variety of audio understanding tasks but continue to struggle with temporal reasoning, a fundamental capability central to human auditory perception. Understanding the causes of these failures remains challenging as existing benchmarks report performance gaps without probing underlying mechanisms. To address this, we introduce a benchmark with 1,657 questions across three foundational tasks designed specifically for mechanistic analysis. Examining model outputs across varying input settings (behavioral analysis) reveals that models often under-utilize audio when textual cues are available. We also provide the first causal mechanistic analysis of temporal reasoning failures in LALMs. Comparing attention upweighting against scaling, we find that redistributing attention across audio tokens is more effective than increasing audio attention. Targeting task-relevant tokens yields further gains. These findings suggest that modality imbalance alone cannot explain failures. Attention scaling at bottleneck layers improves accuracy from 55.9% to 59.1% without fine-tuning, demonstrating a promising direction for future work.

16.
arXiv (CS.AI) 2026-06-19

AI-enhanced tuning of quantum dot Hamiltonians toward Majorana modes

arXiv:2601.02149v4 Announce Type: replace-cross Abstract: We propose a neural network-based model capable of learning the broad landscape of working regimes in quantum dot simulators, and using this knowledge to autotune these devices - based on transport measurements - toward obtaining Majorana modes in the structure. The model is trained in an unsupervised manner on synthetic data in the form of conductance maps, using a physics-informed loss that incorporates key properties of Majorana zero modes. We show that, with appropriate training, a deep vision-transformer network can efficiently memorize relation between Hamiltonian parameters and structures on conductance maps and use it to propose parameters update for a quantum dot chain that drive the system toward topological phase. Starting from a broad range of initial detunings in parameter space, a single update step is sufficient to generate nontrivial zero modes. Moreover, by enabling an iterative tuning procedure - where the system acquires updated conductance maps at each step - we demonstrate that the method can address a much larger region of the parameter space.

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

Catastrophic Forgetting is Low-Rank: A Function-Space Theory for Continual Adaptation

arXiv:2606.18024v1 Announce Type: cross Abstract: Catastrophic forgetting in continual adaptation is usually studied through parameter drift, replay, or distillation, but these views do not identify which output-space directions are vulnerable. We give a function-space account in the NTK regime: new-task training induces old-task prediction drift through the cross-task kernel, yielding a closed-form predictor for the forgetting vector before any new-task gradient step. In frozen-backbone linear-head PEFT-CL, where the model is linear in the trainable parameters, the predictor is exact up to numerical precision; for nonlinear adapters/full fine-tuning, it is a local NTK approximation. The same expression reveals that forgetting concentrates in a small number of old-task NTK eigenmodes and under frozen linear heads gives a Kronecker scaling rule for the vulnerable rank. These results clarify the relation to prior NTK-overlap theory, explain why parameter-space regularizers can miss output-space interference, and motivate a targeted spectral regularizer.

18.
arXiv (CS.CL) 2026-06-12

NTS-CoT: Mitigating Hallucinations in LLM-based News Timeline Summarization with Chain-of-Thought Reasoning

The rapid updates of online news make tracking event developments challenging, highlighting the need for timeline summarization (TLS). Hallucinations, where LLM-generated content deviates from source news, still remain a critical issue in LLM-based TLS and are not well studied in existing works. To bridge this gap, we identify two primary types of hallucinations: unfaithful content during news summarization and information omission in date-event summarization. Then, we propose NTS-CoT, a novel framework that leverages Chain-of-Thought (CoT) reasoning to mitigate hallucinations in TLS. The framework consists of three key modules: i) Element-CoT to capture essential news elements for faithful summarization, ii) Date Selection to combine temporal saliency and event prominence for timestamp selection, and iii) Causal-CoT to infer causal relationships and reduce omissions in date-event summarization. Extensive experiments, including quantitative analysis on three TLS benchmarks and human evaluation, demonstrate that NTS-CoT outperforms state-of-the-art baselines, effectively mitigating hallucinations and improving LLM-based TLS performance. Our source code is available at https://anonymous.4open.science/r/NTS-CoT .

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

Folded Transport MCMC: Eliminating Label Switching by Sampling on a Fundamental Domain

Authors:

arXiv:2606.04307v2 Announce Type: replace Abstract: In Bayesian mixture models and other exchangeable-component models, the posterior is invariant under permutation of component labels, creating m! equivalent modes-the label-switching problem. Standard MCMC methods either mix poorly across these modes or rely on post-hoc relabelling that cannot guarantee the sampler has converged. We propose Folded Transport MCMC (FolT-MCMC), which eliminates label switching before sampling by restricting the Markov chain to a fundamental domain-a sorted or reflected subspace containing exactly one representative from each symmetric mode. The proposal is a learned normalising flow whose density is symmetrised over the group orbits, ensuring correct targeting on the reduced space. We show that this construction preserves a computable convergence diagnostic based on the oscillation of the log-density ratio, and that the diagnostic becomes sharper on the fundamental domain whenever the original-space flow under-covers one or more symmetric modes. Experiments on Gaussian mixtures (d=2-20), label-switching targets (up to 24 equivalent modes), a standard Bayesian three-component mixture posterior, and real accelerometer data from a supertall building show improvement ratios of 2x to 145x, with the folded diagnostic stable across dimensions while the unfolded diagnostic collapses.

20.
arXiv (quant-ph) 2026-06-15

Stab-QRAM: A Clifford-Only Quantum Oracle for Affine Boolean Data

arXiv:2509.26494v3 Announce Type: replace Abstract: Oracle-based quantum algorithms require coherent evaluation of classical functions on superposed inputs, and in fault-tolerant architectures this cost is dominated by non-Clifford gates: generic lookup constructions incur $T$-counts that grow with the data size. Here we show that affine Boolean functions $f(\mathbf{x})=A\mathbf{x}+\mathbf{b}$ over $\mathbb{F}_2$ – the algebraic core of parity checks, linear feedback shift registers, and cipher linear layers – are exactly the functions admitting computational-basis-preserving Clifford oracles, and we develop this correspondence into Stab-QRAM, a compiler mapping a specification $(A,\mathbf{b})$ to an ancilla-free circuit of CNOT and $X$ gates with zero $T$-count. Via K\"{o}nig's edge-coloring theorem, the compiled schedule provably attains the minimum depth for its gate set. Case studies spanning Simon-type oracles, block-encodings of $X$-type coset operators, and syndrome extraction for CSS codes show one compiler serving the algorithm, primitive, and error-correction layers of the quantum stack.

21.
arXiv (quant-ph) 2026-06-16

Semiclassical Gravity Efficiently Solves $\mathsf{NP}$-Complete Problems

arXiv:2606.14806v1 Announce Type: cross Abstract: Assuming the gravitational field is classical and that it couples to quantum fields via the semiclassical Einstein field equations, we show that the weak-field dynamics of a massive and non-relativistic qubit can in principle be used to solve an $\mathsf{NP}$-complete problem in polynomial time. We attribute this vast computational power to the non-linear dynamics afforded by the semiclassical Einstein field equations. Consequently, the above two assumptions entail a violation of the Physical Extended Church–Turing Thesis, which we regard as evidence for the quantization of gravity.

22.
arXiv (CS.CV) 2026-06-17

BrainWorld: A Structural-Prior-Conditioned Generative Model for Whole-Brain 4D fMRI Dynamics

Whole-brain 4D fMRI generation is valuable for modeling functional brain dynamics, yet existing fMRI foundation models mainly target representation learning and downstream prediction rather than conditional predictive generation. We introduce BrainWorld, a structural-prior-conditioned generative model for whole-brain 4D fMRI dynamics. BrainWorld uses sMRI as subject-level anatomical context to guide future fMRI generation, integrating structural information into the denoising process rather than treating it as a parallel modality. Evaluated on 22 datasets spanning diverse cohorts and brain states, BrainWorld generates stable 4D fMRI trajectories up to 400 frames, improves downstream performance through generated-example augmentation, and learns transferable multimodal representations that outperform baselines. Together, these results establish BrainWorld as a condition-aware generative framework for long-horizon brain dynamics modeling and multimodal representation learning.

23.
medRxiv (Medicine) 2026-06-15

Longitudinal monitoring exposes correlated temporal protein variations in the female plasma proteome

The plasma proteome is a valuable resource for assessment of the physiological state of the donor. Containing hundreds of different proteins of variable concentrations, it displays substantial inter-donor differences in individual protein levels, making each plasma proteome highly donor-specific. Less is known about intra-donor variability in the plasma proteome over time, although such variations may even be more indicative of a changing physiological state. Here we assessed data obtained from the TIMES cohort, comprising 51 apparently healthy participants monitored monthly over 12 months, focusing especially on temporal variations in blood protein levels. Most strikingly, we observed that several women in this cohort revealed strongly correlated temporal variations in their plasma proteome, including most notably PZP, SHBG, FETUB, AGT, SERPINA6, SERPINA7, CP, APOL1 and KNG1, with levels sometimes fluctuating by more than 20-fold. In contrast, such variations were absent in men. Some of the fluctuating proteins have been known to be hormone-regulated (e.g., PZP, SHBG), but for others this was not yet fully clear. Through the tight co-variation observed for these proteins in the plasma proteome of women, we can conclude that all these proteins are similarly hormone regulated. The findings reported here not only corroborate previous studies showing estrogen-dependent regulation of several plasma proteins, but also extend this category to include also CP, APOL1, and KNG1. As these latter have been often proposed as candidate biomarkers, they should be validated in sex-balanced cohorts and interpreted with caution, especially in large-scale plasma proteomics studies wherein often only one or a few sampling time points are measured per donor.

24.
bioRxiv (Bioinfo) 2026-06-14

FENNEC: Fine-Tuned Ensemble Neural Networks Accelerate Chemically Modified siRNA Design and Screening

Small interfering RNAs (siRNAs) are a clinically validated therapeutic modality, yet designing potent chemically modified siRNAs remains a costly and iterative process, limited by scarce public data. Computational prediction of siRNA efficacy is therefore essential for rational design and accelerated preclinical development. However, despite the critical role of chemical modifications in therapeutic performance, current state-of-the-art machine learning methods either are not designed to model the chemical diversity of therapeutic siRNAs, or exhibit poor generalization performance. Here, we present FENNEC (Fine-Tuned Ensemble of Neural Networks for siRNA Efficiency Characterization), a machine-learning framework for predicting siRNA activity across chemically diverse design spaces. To support this effort, we curated the largest patent-derived dataset to date of chemically modified siRNAs from 42 patents using OCR-based table extraction and stringent filtering. FENNEC combines temporal convolutional networks with thermodynamic descriptors, experimental covariates, and embeddings from RNA foundation models to capture both local chemical determinants and broader target-context information. Importantly, we show that language-model-derived embeddings provide meaningful higher-order representations of target transcripts, particularly in data-scarce settings. FENNEC achieved robust predictive performance across both gene-level and scaffold-level validation settings, with additional experimental validation on a novel AHSA1-targeting dataset further supporting its generalizability across chemically modified siRNAs. In benchmarking, FENNEC outperformed classical machine-learning and state-of-the-art deep learning models, demonstrating generalization to unseen chemistry. Model interpretation recovered established design principles, including position-specific effects of glycol nucleic acid, 2'-fluoro modifications, and phosphorothioate backbones. Furthermore, in silico perturbation analyses suggest that FENNEC can serve not only as a predictive model, but also as an oracle for the design and optimization of chemically modified siRNAs. Together, our work addresses a key gap in the field by enabling chemically aware deep learning for siRNA design, supported by a large and diverse collection of chemically modified siRNA measurements.

25.
arXiv (CS.AI) 2026-06-16

SPRI: SVD-Partitioned Residual Initialization for Data-Constrained MoE Upcycling

arXiv:2606.16456v1 Announce Type: cross Abstract: Mixture-of-Experts (MoE) models enable efficient scaling, but training them from scratch remains prohibitively expensive. MoE upcycling mitigates this cost by converting pretrained dense models into sparse MoE models. However, existing upcycling methods typically rely on large-scale continued training and often perform poorly under data-constrained supervised adaptation, due to either homogeneous experts or overly disruptive perturbations to pretrained parameters. In this setting, effective upcycling must leverage pretrained weight structure while introducing sufficient diversity among routed experts. To this end, we propose SVD-Partitioned Residual Initialization (SPRI), which distributes SVD-partitioned residuals derived from pretrained feed-forward network (FFN) weights across routed experts, introducing controlled expert diversity grounded in pretrained spectral structure. We further introduce a two-stage training strategy to improve adaptation stability. We evaluate SPRI on multilingual speech-to-text translation, where limited supervised data challenges MoE upcycling and multiple target languages provide natural routing heterogeneity. On CoVoST2 across 15 En-to-XX directions, SPRI improves average BLEU and COMET over fully fine-tuned dense models by 2.58 and 3.32 points, respectively, and outperforms the prior best MoE upcycling baseline by 3.39 BLEU and 4.34 COMET points.