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01.
arXiv (CS.LG) 2026-06-12

Deep Learning-based Algebraic Reynolds Stress Closures for RANS Simulations of Turbulent Flows

arXiv:2605.26358v2 Announce Type: replace-cross Abstract: Turbulence is ubiquitous in engineering and science, yet direct simulation is prohibitively expensive. The Reynolds-averaged Navier-Stokes (RANS) equations provide savings exceeding ten orders of magnitude but introduce unclosed terms (the closure problem). Offline-trained machine-learning (ML) closures suffer distribution shift in predictive simulations, while ML methods that bypass the governing equations struggle to generalise from scarce high-fidelity data. We develop a physics-derived deep learning closure model for RANS, the Deep Algebraic Reynolds Stress Model (DARSM), which can be trained on small datasets and accurately generalise across Reynolds numbers, to unseen geometries, and to different flow regimes. A neural network maps flow invariants to empirical parameters in an implicit algebraic Reynolds stress equation, derived from the Reynolds stress transport equations under the weak-equilibrium assumption, imposing physics-based structure on the ML closure. End-to-end optimisation through the governing PDEs and the coupled implicit closure eliminates distribution shift, but both unrolled and implicit automatic differentiation fail on the stiff coupled solver. We derive adjoint equations that exploit the solver's implicit-explicit structure for efficient optimisation. On canonical square-duct and periodic-hill benchmarks, DARSM reduces average test velocity error over baseline RANS by $2$-$4\times$ across Reynolds number, geometries, and flow regimes, with peak case-level reductions of $12\times$. The model trained on attached, anisotropy-dominated flows (square duct) accurately generalises without retraining to separated flows (periodic hills), a regime change in the underlying physics. DARSM also outperforms five established ML methods: offline training, tensor-basis neural networks, field-inversion machine learning, DeepONets, and physics-informed neural networks.

02.
arXiv (math.PR) 2026-06-12

Exact Fourier dimensions of dyadic Mandelbrot cascades under minimal integrability

arXiv:2606.08683v2 Announce Type: replace Abstract: We determine the Fourier dimension of dyadic Mandelbrot cascades under the minimal Kahane-Peyriere integrability condition. The interval theorem is proved in a vector-valued dyadic cascade model in which sibling weights may have arbitrary dependence. For every balanced energy-admissible vector law, almost surely on non-extinction, dim_F(mu)=dim_E(mu)=dim_2(mu)=D_E(X). In the canonical scalar case, under W>=0, E W=1, E[W log_2^+ W]

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

Context-Aware Markov VAE for CSI Compression in Wireless Systems

arXiv:2606.16607v1 Announce Type: cross Abstract: This paper considers neural channel state information (CSI) compression for time-varying massive multiple-input multiple-output (MIMO) channels in frequency division duplex (FDD) systems with limited feedback resources. The main challenge lies in obtaining a compact and efficient representation of the CSI given that it exhibits strong temporal correlation across successive snapshots. Existing memoryless compression models do not exploit this property, while simple temporal extensions often incorporate multiple observations without explicitly modeling the latent dynamics. We propose a context-aware compression framework based on a k-memory Markov variational autoencoder (k-MMVAE), which uses a finite temporal window to capture the evolution of CSI in the latent space. The model introduces Markov-structured latent dynamics with finite memory, enabling efficient use of temporal dependencies for compression. Simulation results show that the proposed approach improves target CSI reconstruction performance compared to memoryless and weakly sequential baselines, particularly at low and moderate compression rates. These results suggest that explicit latent temporal modeling can provide an effective mechanism for CSI compression under limited feedback constraints.

04.
bioRxiv (Bioinfo) 2026-06-24

BATTLE-AMP: Benchmarking Antimicrobial Peptide Predictors

As antimicrobial resistance outpaces antibiotic development, antimicrobial peptides (AMPs) have emerged as a promising class of alternative antibacterials, and computational predictors are increasingly used to prioritize AMP candidates. Such predictors are typically evaluated on binary AMP/non-AMP classification, which does not test whether they can identify peptides with clinically relevant potency against specific pathogens. We present BATTLE-AMP, a benchmarking framework that evaluates AMP predictors against experimentally measured minimum inhibitory concentrations (MICs) across clinically relevant bacterial species and strains. We surveyed 48 published methods, finding fewer than 25% reproducible, and benchmarked 10 model families (21 variants) using experimental MIC data, synthetic sequence perturbations, activity cliff analyses, and all-atom molecular dynamics (MD) simulations. Four findings emerge: (i) models trained on MIC data outperform binary classifiers regardless of architecture; (ii) the best model depends on the target pathogen, so model selection must be guided by the biological question; (iii) most models cannot distinguish active peptides from inactive sequences with identical amino acid composition; and (iv) activity cliffs remain unresolved by both machine learning and MD, marking a limit of current computational methods. BATTLE-AMP is released as an open Snakemake framework at https://github.com/szczurek-lab/battleamp-snakemake for benchmarking new models and scoring novel candidate libraries.

05.
arXiv (quant-ph) 2026-06-12

The Pound-Drever-Hall Method for Superconducting-Qubit Readout

arXiv:2512.03138v3 Announce Type: replace Abstract: Scaling quantum computers to large sizes requires the implementation of many parallel qubit readouts. Here we present an ultrastable superconducting-qubit readout method using the multi-tone self-phase-referenced Pound-Drever-Hall (PDH) technique, originally developed for use with optical cavities. In this work, we benchmark PDH readout of a single transmon qubit, using room-temperature heterodyne detection of all tones to reconstruct the PDH signal. We demonstrate that PDH qubit readout is insensitive to microwave phase drift, displaying $0.73^\circ$ phase stability over 2 hours, and capable of single-shot readout in the presence of phase errors exceeding the phase shift induced by the qubit state. We show that the PDH sideband tones do not cause unwanted measurement-induced state transitions for a transmon qubit, leading to a potential signal enhancement of at least $14$~dB.

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

Would you still call this Dax? Novel Visual References in VLMs and Humans

Vision-language models (VLMs), like human learners, are frequently exposed to new visual concepts, but how they map novel visual references to language after exposure remains largely underexplored, particularly when those references contradict prior knowledge from pre-training. To study this, we present the Novel Visual References Dataset (NVRD): 19,176 images spanning 90 visual concepts across different levels of visual novelty, each with up to 20 increasingly perturbed versions of the original object to probe generalization. Unlike prior work on visual augmentations of familiar concepts, NVRD comprises entirely novel, open-ended stimuli constructed from scratch, mirroring how humans encounter genuinely new concepts. We evaluate 3 open- and 2 closed-source models alongside 2,400 human judgments for direct human-model comparison, and find that (i) models struggle to acquire novel concepts in-context when they contradict prior knowledge, and (ii) while models and humans show correlated sensitivity to visual perturbations, models significantly overgeneralize, extending learned labels to stimuli that humans reject. We contribute NVRD as a corpus and benchmark for research on visual concept learning in both humans and machines.

07.
arXiv (quant-ph) 2026-06-25

Asymmetry dynamics and nonequilibrium symmetry-breaking phase transitions

arXiv:2606.07188v2 Announce Type: replace-cross Abstract: In classical settings, the Mpemba effect occurs when a hotter system cools faster than an initially colder one. In quantum systems, this effect can be reinterpreted exploiting the concept of symmetries, with the asymmetry of a subsystem playing the role of temperature. A quantum Mpemba effect arises when a more asymmetric state restores the symmetry faster than a less asymmetric one. Previous work mainly focuses on closed systems characterized by thermal equilibration and Hamiltonian symmetries. In this paper, we analyze the dynamics of asymmetry in an open quantum many-body system featuring symmetry breaking and uncover dynamical behavior that appears to be unique to these settings. In the symmetric phase, we demonstrate the existence of a quantum Mpemba effect, which emerges as a direct consequence of a non-monotonic evolution of the asymmetry. In the broken-symmetry phase, we analyze the imbalance between the system's ability to increase or to decrease its asymmetry. Our results extend the notion of quantum Mpemba effects to open quantum many-body systems exhibiting symmetry-breaking phase transitions and establish them as a platform for observing and controlling anomalous relaxation phenomena.

08.
arXiv (math.PR) 2026-06-16

Scaling Limits of Bivariate Nearly-Unstable Hawkes Processes and Applications to Rough Volatility

arXiv:2605.03703v3 Announce Type: replace Abstract: We study a pair of nearly-unstable Hawkes processes coupled through a one-directional, or triangular, cross-excitation: the first component evolves autonomously and excites the second, but not conversely. Each component is self-exciting through a heavy-tailed memory kernel, and the two kernels are allowed to have different tail indices, so that the limiting components exhibit genuinely different degrees of roughness. As the system approaches criticality, we prove that the suitably rescaled intensity vector converges weakly to the unique solution of a coupled system of stochastic Volterra equations of rough-volatility type. The first limiting component is autonomous, while the second is driven both by its own noise and by an inherited noise transmitted from the first component through an effective cross-kernel. This cross-kernel is the convolution of the two limiting Mittag-Leffler kernels and therefore combines the two memory structures. As a consequence, we obtain a short-time cross-decorrelation law: although the two components are coupled, their functional correlation vanishes at small time scales at an explicit polynomial rate. This time-dependent correlation distinguishes the limit from independent rough processes and from classical bivariate rough models with constant Brownian correlation.

09.
arXiv (CS.LG) 2026-06-17

Learning Upper Lower Value Envelopes to Shape Online RL: A Principled Approach

arXiv:2510.19528v2 Announce Type: replace-cross Abstract: We investigate the fundamental problem of leveraging offline data to accelerate online reinforcement learning - a direction with strong potential but limited theoretical grounding. Our study centers on how to learn and apply value envelopes within this context. To this end, we introduce a principled two-stage framework: the first stage uses offline data to derive upper and lower bounds on value functions, while the second incorporates these learned bounds into online algorithms. Our method extends prior work by decoupling the upper and lower bounds, enabling more flexible and tighter approximations. In contrast to approaches that rely on fixed shaping functions, our envelopes are data-driven and explicitly modeled as random variables, with a filtration argument ensuring independence across phases. The analysis establishes high-probability regret bounds determined by two interpretable quantities, thereby providing a formal bridge between offline pre-training and online fine-tuning. Empirical results on tabular MDPs demonstrate substantial regret reductions compared with both UCBVI and prior methods while remaining competitive with related approaches.

10.
bioRxiv (Bioinfo) 2026-06-19

Evaluation of analysis modes for RNA coexpression in single-cell and bulk tissue

Coexpression of transcripts presents the most common means of computational inference of transcription factor regulation, and is often combined with other data types to infer regulatory networks. With the growing popularity of single-cell approaches, there are questions about how best to extract coexpression information from the data. Recently we reported a simulation study that explored the differences among coexpression performed at different levels: across single cells (xCell, per cell type), across subjects from pseudobulked single-cell data (xSubject, per cell type), or across subjects using bulk tissue samples (xBulk). Here we test predictions made by those models using real data. We consider both preservation (consistency of coexpression findings across different levels of analysis of the same data) and replicability across independent studies, as well as biological interpretability. We find that preservation across levels is limited, indicating the choice of analysis level will affect outcomes. We show that xCell coexpression is more replicable across studies compared to xSubject. xBulk coexpression is dominated by patterns driven by variability in cellular composition and fails to capture much coexpression that is reliably detected at finer resolutions. While all modes of analysis exhibit some enrichment for known regulatory relationships, it was highest with the xCell mode. Finally, we present a case study of the effect of analysis modes on a schizophrenia-associated pattern, reinforcing the importance of analytic choices in the interpretation and replicability of coexpression analyses. Together with our modeling study, this work emphasizes the importance of understanding sources of expression covariation as they relate to the goals of the analysis, and recommend single-cell-based data with biological replicates should be the focus of attempts to infer dynamic regulatory interactions that are more likely to be replicable by others.

11.
medRxiv (Medicine) 2026-06-18

Predicting Motor Recovery After Stroke: Utility and Limits of Corticospinal Tract Biomarkers

Background: Corticospinal tract (CST) damage is a major cause of post-stroke motor deficits. However, it remains unclear which estimates of CST damage best predict motor recovery, especially regarding different aspects of motor control. While conventional CST-lesion metrics offer superior feasibility, data-driven machine learning (ML) approaches may better capture patients propensity for task-specific recovery with important implication for their use as future clinical biomarkers. Methods: Providing the first direct longitudinal comparison of these approaches based exclusively on CST-lesion patterns, we evaluated six conventional CST-lesion metrics and a voxel-wise ML approach using clinical MRI data from 127 acute ischemic stroke patients. Acute impairment and outcome (>3 months post-stroke) were assessed for basal and complex motor functions. Conventional CST-lesion metrics and ML were used to predict task-specific motor impairment and outcome. Results: All conventional CST-lesion metrics correlated significantly with both acute impairment and motor outcome across motor domains, with metrics weighted for CST narrowing and tract probability performing best. However, predictive performance for unseen patients was low. ML outperformed conventional markers in predicting acute impairment across motor domains and basal motor outcome, but failed to predict complex motor outcome. Topographically, predictive voxels clustered within and above the posterior limb of the internal capsule, with distinct CST subregions associated with basal versus complex motor impairment, consistent with a task-specific somatotopic organization. Conclusions: The predictive utility of CST biomarkers was task- and timepoint-dependent. While ML may improve predictive performance, complex motor outcome remained difficult to predict, likely reflecting greater reliance on distributed cortical reorganization beyond the CST. By revealing task-specific CST subregions, voxel-wise ML provides an anatomically informed foundation for future predictive models. Such future models should combine CST biomarkers with measures of broader motor network integrity to enable individualized prognosis tailored to specific motor domains and recovery stages.

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

SPARK: Spatial Policy-driven Adaptive Reinforcement learning for Knowledge distillation

Low-bit quantization enables deployment of image restoration (IR) networks on resource-constrained devices, but introduces rounding noise that disproportionately degrades high-frequency regions such as edges and fine textures. Existing knowledge distillation (KD) methods apply distillation signals uniformly across all spatial locations, overlooking the varying reconstruction difficulty across image regions. To address this, we propose SPARK (Spatial Policy-driven Adaptive Reinforcement Learning for Knowledge Distillation), a framework that adaptively allocates distillation effort using a lightweight reinforcement learning (RL) policy network. At each training step, a difficulty feature extractor computes four signals, namely Laplacian variance, pixel variance, student reconstruction error, and teacher-student knowledge gap, which are fed into a compact policy CNN that produces a stochastic spatial weight map to modulate the KD loss during quantization-aware training (QAT). SPARK is IR task-agnostic, adds no inference cost, and integrates into any existing QAT pipeline without architectural changes. Experiments on benchmark datasets demonstrate that SPARK consistently outperforms PTQ, QAT, and state-of-the-art (SOTA) KD approaches across multiple student architectures, achieving reconstruction quality closest to the full-precision teacher under significant computational constraints.

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

Dynamic Free-Rider Detection in Federated Learning via Simulated Attack Patterns

arXiv:2604.04611v2 Announce Type: replace Abstract: Federated learning (FL) enables multiple clients to collaboratively train a global model by aggregating local updates without sharing private data. However, FL often faces the challenge of free-riders, clients who submit fake model parameters without performing actual training to obtain the global model without contributing. Chen et al. proposed a free-rider detection method based on the weight evolving frequency (WEF) of model parameters. This detection approach is a leading candidate for practical free-rider detection methods, as it requires neither a proxy dataset nor pre-training. Nevertheless, it struggles to detect ``dynamic'' free-riders who behave honestly in early rounds and later switch to free-riding, particularly under global-model-mimicking attacks such as the delta weight attack and our newly proposed adaptive WEF-camouflage attack. In this paper, we propose a novel detection method S2-WEF that simulates the WEF patterns of potential global-model-based attacks on the server side using previously broadcasted global models, and identifies clients whose submitted WEF patterns resemble the simulated ones. To handle a variety of free-rider attack strategies, S2-WEF further combines this simulation-based similarity score with a deviation score computed from mutual comparisons among submitted WEFs, and separates benign and free-rider clients by two-dimensional clustering and per-score classification. This method enables dynamic detection of clients that transition into free-riders during training without proxy datasets or pre-training. We conduct extensive experiments across three datasets and five attack types, demonstrating that S2-WEF achieves higher robustness than existing approaches.

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

Unlocking air traffic flow prediction through microscopic aircraft-state modeling

arXiv:2605.10083v2 Announce Type: replace Abstract: Short-term air traffic flow prediction in terminal airspace is essential for proactive air traffic management. Existing approaches predominantly model traffic flow as aggregated time series. However, traffic dynamics are governed by aircraft states and their interactions in continuous airspace. Such aggregation obscures fine-grained information, including aircraft kinematics, boundary interactions, and control intent. Here we present AeroSense, a state-to-flow modeling paradigm that predicts future traffic flow directly from instantaneous airspace situations represented as dynamic sets of aircraft states derived from ADS-B trajectories. By establishing an end-to-end mapping from microscopic aircraft states to future regional traffic flow, AeroSense preserves aircraft-level dynamics while naturally accommodating varying traffic density without relying on historical look-back windows. Experiments on a large-scale real-world dataset show that AeroSense exhibits admirable predictive accuracy and robustness over aggregation-based forecasting approaches, particularly during high-density traffic periods. These findings suggest that aircraft-state situation modeling provides a promising alternative to conventional time-series forecasting in air traffic flow management.

15.
arXiv (quant-ph) 2026-06-16

Spectrally Corrected Polynomial Approximation for Quantum Singular Value Transformation

arXiv:2603.03998v2 Announce Type: replace Abstract: Quantum Singular Value Transformation (QSVT) provides a unified framework for applying polynomial functions to the singular values of a block-encoded matrix. QSVT prepares a state proportional to $\bA^{-1}\bb$ with circuit depth $O(d\cdot\mathrm{polylog}(N))$, where $d$ is the polynomial degree of the $1/x$ approximation and $N$ is the size of $\bA$. Current polynomial approximation methods are over the continuous interval $[a,1]$, giving $d = O(\sqrt{\kap}\log(1/\varepsilon))$, and make no use of any properties of $\bA$. We observe here that QSVT solution accuracy depends only on the polynomial accuracy at the eigenvalues of $\bA$. When all $N$ eigenvalues are known exactly, a pure spectral polynomial $p_{S}$ can interpolate $1/x$ at these eigenvalues and achieve unit fidelity at reduced degree. But its practical applicability is limited. To address this, we propose a spectral correction that exploits prior knowledge of $K$ eigenvalues of $\bA$. Given any base polynomial $p_0$, such as Remez, of degree $d_0$, a $K\times K$ linear system enforces exact interpolation of $1/x$ only at these $K$ eigenvalues without increasing $d_0$. The spectrally corrected polynomial $p_{SC}$ preserves the continuous error profile between eigenvalues and inherits the parity of $p_0$. QSVT experiments on the 1D Poisson equation demonstrate up to a $5\times$ reduction in circuit depth relative to the base polynomial, at unit fidelity and improved compliance error. The correction is agnostic to the choice of base polynomial and robust to eigenvalue perturbations up to $10\%$ relative error. Extension to the 2D Poisson equation suggests that correcting a small fraction of the spectrum may suffice to achieve fidelity above $0.999$.

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

No One-Size-Fits-All Neurons: Task-based Neurons for Artificial Neural Networks

arXiv:2405.02369v2 Announce Type: replace-cross Abstract: In the past decade, many successful networks are on novel architectures, which almost exclusively use the same type of neurons. Recently, more and more deep learning studies have been inspired by the idea of NeuroAI and the neuronal diversity observed in human brains, leading to the proposal of novel artificial neuron designs. Designing well-performing neurons represents a new dimension relative to designing well-performing neural architectures. Biologically, the brain does not rely on a single type of neuron that universally functions in all aspects. Instead, in our brain, neurons are often task-based. In this study, we address the following question: since the human brain is a task-based neuron user, can the artificial network design go from the task-based architecture design to the task-based neuron design? Since methodologically there are no one-size-fits-all neurons, given the same structure, task-based neurons can enhance the feature representation ability relative to the existing universal neurons due to the intrinsic inductive bias for the task. Specifically, we propose a two-step framework for prototyping task-based neurons. As the initial step, we evaluate the proposed framework using polynomials as base functions. Empirically, systematic experimental results on synthetic data, classic benchmarks, and real-world applications show that the proposed task-based neuron design is not only feasible but also delivers competitive performance over other state-of-the-art models.

17.
bioRxiv (Bioinfo) 2026-06-19

Nickel-Driven Dynamics of Urease in Sporosarcina pasteurii: Integrated Computational and Experimental Insights

Urease is a nickel-dependent enzyme that plays an important role in urea hydrolysis and in a process named as microbial-induced calcium carbonate precipitation (MICP), which is widely used in sustainable environmental biotechnology. Despite its ecological importance, urease powers Biogrout (biocementation), a promising green technology for soil stabilization and infrastructure repair. Yet, the relationship between nickel availability, enzyme activation, and bacterial fitness remains poorly understood. In this study, we reveal a striking dual effect of nickel on Sporosarcina pasteurii: while high Ni2+ concentrations strongly inhibit growth (IC50 {approx} 637.7 {micro}M), they simultaneously boost specific urease activity up to six-fold. This uncoupling between biomass and enzymatic efficiency highlights a previously overlooked adaptive strategy under metal stress. Using structural bioinformatics and molecular docking, we show that Ure1–the catalytic subunit–exhibits the strongest nickel affinity (-4.3 kcal{middle dot}mol-1), supported by highly conserved active-site residues, whereas accessory proteins UreE and UreG display moderate and weak binding, consistent with their roles in metal delivery and GTP-dependent maturation. In addition, microscopic observations confirmed that calcium carbonate precipitation was most pronounced at intermediate nickel concentrations (approximately 400-1000 {micro}M), whereas higher concentrations ([≥]1000-1300 {micro}M) led to reduced mineral formation due to loss viable cells. Taken together, these results indicates that nickel availability controls both urease activation and bacterial fitness, and that an optimal balance is required to maximize biomenerilization efficiency in environmental applications, particularly in biocementation technology.

18.
arXiv (quant-ph) 2026-06-16

Conditions for Unitarity in Timeless Quantum Theory

arXiv:2504.01579v3 Announce Type: replace Abstract: Quantum timeless approaches solve the problem of time by recovering the usual unitary evolution of quantum theory relative to a clock in a stationary quantum Universe. For some Hamiltonians of the Universe, such as those including an interaction term with the clock, the dynamics is substantially altered and can be non-unitary. This work derives necessary and sufficient conditions for the relative dynamics to be unitary and finds the general form of the unitary evolution operator. A physical interpretation of these conditions is given in terms of the clock's rate. Unitary dynamics is associated with rates that are constant in time and independent of the clock's internal structure.

19.
medRxiv (Medicine) 2026-06-22

The Protective Role of Belonging and Socioeconomic Status in Dropout Intent Among Minority Ethnic Students: A Mixed Methods Study

Improving minority ethnic student retention is a global higher education priority. This mixed-methods study investigated how institutional belonging and socioeconomic status interact to shape dropout intentions among minority university students in the UK (N = 182). Quantitative results revealed that perceived course difficulty and lower subjective socioeconomic status were the strongest predictors of dropout intent. While the interaction between socioeconomic status and difficulty was non-significant, qualitative accounts showed distinct structural vulnerabilities. Financial strain restricted social integration, turning socioeconomic disparities into campus isolation. Conversely, representative curricula, diverse peer networks, and stable cultural in-groups (e.g., religious affiliations, living in the parental home) functioned as essential psychological buffers against academic exhaustion and alienation. Universities must shift from transactional models to sustained structural equity to protect vulnerable student groups.

20.
medRxiv (Medicine) 2026-06-24

A Custom Global Screening Array for Integrated Familial Hypercholesterolemia Detection and Polygenic Risk Assessment in a Multi-Ethnic New Zealand Population

Background: Cardiovascular disease (CVD) is the leading cause of mortality in New Zealand, with significant inequities affecting M[a]ori and Pacific peoples. Familial hypercholesterolaemia (FH) affects approximately 1 in 313 individuals globally, yet over 90% remain undiagnosed. Standard polygenic risk scores (PRS) derived from European cohorts may not be portable to diverse ancestries. We developed the HoloQ Omniscan Waka Te Ira, a custom Illumina Global Screening Array (GSA) v3 enriched with FH mutations, coronary artery disease (CAD) PRS markers, and network medicine-derived content. Methods: We customised the GSA v3 by adding 43,437 single nucleotide polymorphisms (SNPs) targeting FH and CAD. Content included 6,717 unique variants in primary FH genes; 14,005 pathogenic or likely pathogenic cardiovascular and pharmacogene variants; and 5,845 copy number variant probes. We further incorporated 5,232 network medicine derived CAD SNPs, 14,806 rare variants for a multiancestry PRS, and 407 globally diverse and population-specific variants. The final design comprised 47,027 target SNPs. Validation utilised large-scale genotype and whole-genome sequencing (WGS) datasets with PRS benchmarking. Results: In a large European-ancestry dataset, we observed high recovery for common PRS loci but low recovery for population-specific founder variants. The array captured 938 (84%) of all pathogenic or likely pathogenic FH variants catalogued in ClinVar, representing a 26.4% expansion beyond the standard backbone array. WGS validation identified additional carriers of rare high impact variants present only in the custom content. The selected CAD PRS model achieved an adjusted area under the receiver operating characteristic curve of 0.786. Conclusion: The HoloQ Omniscan Waka Te Ira enhances detection of clinically relevant FH variants and provides robust PRS coverage. The low recovery of population-specific alleles underscores the necessity of this custom array for equitable genomic medicine in New Zealand's multi-ethnic population.

21.
arXiv (CS.LG) 2026-06-16

Convex Approximation of Two-Layer ReLU Networks for Hidden State Differential Privacy

arXiv:2407.04884v4 Announce Type: replace Abstract: The hidden state threat model of differential privacy (DP) assumes that the adversary has access only to the final trained machine learning (ML) model, without seeing intermediate states during training. However, the current privacy analyses under this model are restricted to convex optimization problems, reducing their applicability to multi-layer neural networks, which are essential in modern deep learning applications. Notably, the most successful applications of the hidden state privacy analyses in classification tasks have only been for logistic regression models. We demonstrate that it is possible to privately train convex problems with privacy-utility trade-offs comparable to those of 2-layer ReLU networks trained with DP stochastic gradient descent (DP-SGD). This is achieved through a stochastic approximation of a dual formulation of the ReLU minimization problem, resulting in a strongly convex problem. This enables the use of existing hidden state privacy analyses and provides accurate privacy bounds also for the noisy cyclic mini-batch gradient descent (NoisyCGD) method with fixed disjoint mini-batches. Empirical results on benchmark classification tasks demonstrate that NoisyCGD can achieve privacy-utility trade-offs on par with DP-SGD applied to 2-layer ReLU networks.

22.
medRxiv (Medicine) 2026-06-16

Presurgical immune biomarkers associated with pain intensity and pain interference recovery after total knee arthroplasty: findings from the PRIME-KNEE study

Chronic postsurgical pain (CPSP) prevalence after total knee arthroplasty (TKA) is >20%. Circulating immune biomarkers are known factors of musculoskeletal pain but poorly understood as CPSP predictors. This prospective, longitudinal study of 203 patients s/p TKA tested presurgical plasma biomarkers associated with 6-month CPSP, using promising approaches from geriatrics biomarker research: expected recovery differential (ERD; resilience outcome) and penalized, machine-learning regularization modeling (elastic net and LASSO regression). Forty-nine presurgical candidate biomarkers were considered. CPSP was operationalized using ERDs built around PROMIS pain intensity and pain interference, which quantified the difference between observed and expected recovery after accounting for demographic, comorbidity, reserve, and perioperative factors. Plasma/ERDs from ~130 patients revealed 13 biomarkers with the highest selection stability criteria, and either positive or negative (+/-) associations with ERDs. Interleukin (IL) 5 (-) and Lipopolysaccharide-Binding Protein (LBP; +) were associated with both ERDs. Unique associations with pain intensity ERD included Cytomegalovirus-Specific IgG Negative (CMV IGg-; -), Macrophage Inflammatory Protein-1 Beta (MIP1b; -), IL12p70 (-, Cluster of Differentiation 30 (sCD30;-), Interferon alpha 2a (IFN2a;+), and Leukemia Inhibitory Factor (LIF;+). Unique associations with pain interference ERD included Lipopolysaccharide (LPS;-), Activin A (-), IL8 (-), Serum Amyloid A (SAA;-), and IL7 (+). Protein-protein interaction analyses and topology motifs suggest a centralized network with higher-than-expected connectivity, involving IL5, IL7, IL8, MIP1{beta}, and IFN2a, among others. This study proposes rigorous yet feasible approaches to expedite pain biomarker research, and introduces presurgical biomarkers t0 consider in future TKA-CPSP biosignature derivation.

23.
arXiv (CS.CL) 2026-06-25

The Tatoxa System for Text Detoxification in Low-Resource Languages: The Case of Tatar

Text detoxification, the automated detection and mitigation of abusive and harmful content, is essential for ensuring the safety of online communities and protecting users. However, low resource languages such as Tatar have received little research attention. In this paper we present Tatoxa, a novel state-of-the-art system for text detoxification in the Tatar language. Comparative experiments show that the proposed approach outperforms existing open source and proprietary commercial LLMs on key quality metrics. We also introduce a new dataset for text detoxification in Tatar, designed for fine tuning and evaluation in low resource settings. Finally, cross lingual transfer experiments indicate that transfer from other languages, including the culturally close Russian, performs significantly worse than training on native Tatar data even when a large Russian corpus is available.

24.
bioRxiv (Bioinfo) 2026-06-24

V3Cell: A Vision-Guided Virtual 3D Cell Framework for Phenotypic Modeling and Perturbation Prediction

Predicting how organoids respond to chemical perturbations is central to disease modeling and drug discovery. Existing virtual cell models operate at the single-cell level, producing static endpoint predictions from destructive assays. This leaves a critical gap at the organoid scale, where biological identity is defined by tissue-level architecture and continuous developmental dynamics rather than single-cell features. Here we introduce V3Cell, a vision-guided framework that constructs in silico surrogates of organoids directly from non-invasive brightfield microscopy. A foreground-aware model constructs static virtual 3D cells across colon, stomach, and lung organoid lineages. These virtual 3D cells closely match real samples across distributional metrics, micro-texture, and lineage-specific morphometrics, with small effect sizes for most descriptors. A temporal module further predicts developmental fate from as few as six early-frame observations and models fate-conditioned spatiotemporal trajectories that closely recapitulate real perturbation responses. V3Cell requires no omics profiling or fluorescent labeling, establishing a non-invasive brightfield-based paradigm for organoid-scale perturbation prediction. Our code and data are publicly available at https://github.com/Laineyoulu/V3Cell.

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

Loss Landscape Diagnosis for Gradient-Based Gray-Scott System Inversion: Disentangling the Roles of PINN Components

作者:

arXiv:2606.11258v1 Announce Type: new Abstract: Gradient-based inversion of reaction-diffusion systems is typically approached via surrogate models or physics-informed neural networks (PINNs), while the most direct route, backpropagation through the PDE's structure itself, has largely been avoided. We pursue this direct route as a diagnostic probe, backpropagating a steady-state loss through unrolled Gray-Scott simulation to recover its parameters, with no surrogate or neural-network augmentation. Optimization fails to converge, and plotting the landscape directly locates the failure in its geometry – flat plateaus with no gradient signal, bounded by sharp cliffs that align with bifurcation boundaries – a structure that recurs across loss functions and is inherited however the gradients are routed to parameters. Reading this minimal setup as an ablation of PINN, we disentangle each component's role: with the neural network fixed, the residual loss is quadratic in the PDE parameters and yields a smooth landscape, so it alone already avoids the pathology, by implicitly encoding the full PDE dynamics across all initial conditions. The neural network, for its part, cannot repair an ill-posed parameter subspace, and so serves only to complete the observed data – a division of labor not previously made explicit. These findings carry concrete design implications for PINN-type methods and a broader heuristic on when added dimensions actually help.