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01.
bioRxiv (Bioinfo) 2026-06-08

TRACEY: an updated resource for SNARE protein domain annotation with improved HMMs and expanded sequence coverage

Motivation: SNARE proteins catalyse membrane fusion across the eukaryotic endomembrane system, from synaptic vesicle exocytosis to intracellular trafficking, endosomal and vacuolar transport, and autophagy, and their accurate domain annotation depends on the quality of profile models and the sequence diversity behind them. The original SNARE domain classification predates the recent expansion of eukaryotic sequence data, leaving its HMM profiles and subgroup coverage unable to resolve divergent and lineage-specific paralogs. Results: We present an updated release of TRACEY built on a resynchronized, non-redundant collection of 18,915 curated SNARE proteins spanning 1,188 species, together with a consolidated set of 83 HMM profiles, including 43 models for newly defined subgroups, reconstructed through an iterative, mixture-model-driven procedure. In direct comparison with the legacy models, at least ~75% of sequences in every overlapping group scored better with the new HMMs, indicating systematic gains in domain detection. A redesigned web interface adds multiparameter querying, FASTA download, and direct scanning of user-submitted sequences against the curated profiles. Availability and implementation: TRACEY is freely available at https://tracey.unil.ch.

02.
arXiv (math.PR) 2026-06-19

Optimal Sparsification of Gaussian Processes

arXiv:2606.19763v1 Announce Type: new Abstract: We prove an optimal dimension-free sparsification theorem for suprema of centered Gaussian processes. Given a bounded set $T\subseteq\mathbb{R}^n$, we show that the supremum of the canonical Gaussian process on $T$ can be $L^2$-approximated by the supremum of a shifted subprocess indexed by only $\exp(O(1/\varepsilon^2))$ points, with error at most $\varepsilon$ times the Gaussian width of $T$. In particular, the size of the approximating process is independent of both the ambient dimension and the cardinality of the original index set. This improves a recent sparsification theorem of De, Nadimpalli, O'Donnell, and Servedio (2026) by an exponential factor, and we show that the dependence on $\varepsilon$ is tight up to constants in the exponent. As consequences, we obtain an exponentially improved junta theorem for norms over Gaussian space and sharpen results on learning, property testing, and polyhedral approximation of convex sets under the Gaussian measure. The proof is based on an interpolation argument that combines Sudakov's minoration with the Brascamp–Lieb inequality.

03.
arXiv (CS.LG) 2026-06-15

MAD: Manifold Attracted Diffusion

arXiv:2509.24710v3 Announce Type: replace-cross Abstract: Score-based diffusion models are a highly effective method for generating samples from a distribution of images. We consider scenarios where the training data comes from a noisy version of the target distribution, and present an efficiently implementable modification of the inference procedure to generate noiseless samples. Our approach is motivated by the manifold hypothesis, according to which meaningful data is concentrated around some low-dimensional manifold of a high-dimensional ambient space. The central idea is that noise manifests as low magnitude variation in off-manifold directions in contrast to the relevant variation of the desired distribution which is mostly confined to on-manifold directions. We introduce the notion of an extended score and show that, in a simplified setting, it can be used to reduce small variations to zero, while leaving large variations mostly unchanged. We describe how its approximation can be computed efficiently from an approximation to the standard score and demonstrate its efficacy on toy problems, synthetic data, and real data.

04.
arXiv (quant-ph) 2026-06-19

Random Local Stabilizer Codes in Three Dimensions without String or Self-Similar Fractal Logical Operators

作者:

arXiv:2606.19873v1 Announce Type: new Abstract: Quantum error-correcting codes (QECs) are essential components quantum computation and have deep connections to quantum phases of matter. A key obstruction to passive self-correcting QECs is the presence of string logical operators, which can generate logical errors through constant-energy-barrier processes. Haah's Codes (fracton codes) showed that three-dimensional stabilizer codes can forbid such string logical operators, but their translation-invariant structure supports self-similar fractal logical operators with a logarithmic energy barrier. We introduce the qutrit random cubic codes, a family of local qutrit Calderbank-Shor-Steane stabilizer Hamiltonians with similar cube-check structure as Haah's Code 1 but built from spatially varying stabilizers. We prove that these models retain the no-string property and numerically observe that they have properties distinct from translation-invariant fracton codes: the smallest ground-state degeneracy exponent is $k=2$ for odd $L$ and $k=4$ for even $L$; noncontractible plane-logical operators span the entire logical space; and charge-push diagnostics show that the self-similar fractal operators are absent. These results demonstrate that constrained randomness can fundamentally change the nature of stabilizer codes and improve their self-correction properties. They further point to broader families of quantum error-correcting codes and quantum phases beyond canonical topological and fracton orders.

05.
arXiv (CS.AI) 2026-06-17

Functional Equivalence in Attention: A Comprehensive Study with Applications to Linear Mode Connectivity

arXiv:2606.17830v1 Announce Type: cross Abstract: Neural network parameter spaces are inherently non-injective, as distinct parameter configurations can realize identical functions through functional equivalence. While this symmetry is well understood in classical fully connected and convolutional models, it becomes substantially more intricate in modern attention-based architectures. Existing analyses of multihead attention have largely focused on the vanilla formulation, overlooking positional encodings that fundamentally reshape architectural symmetries. In this work, we provide a formal study of functional equivalence in Transformers with positional encodings. Focusing on the two most widely used variants–sinusoidal and rotary positional encodings (RoPE)–we show that sinusoidal encodings preserve the equivalence structure of vanilla attention, whereas rotary encodings significantly reduce the symmetry group, thereby enhancing expressivity. This offers a principled explanation for the growing prominence of RoPE in practice. We further examine how positional encodings affect linear mode connectivity, and through an alignment algorithm, empirically demonstrate that the presence and variability of connectivity across Transformer settings crucially depend on the positional encoding.

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

Uncertainty-Aware Reward Modeling for Stable RLHF

arXiv:2606.19818v1 Announce Type: cross Abstract: Reinforcement learning from human feedback (RLHF) aligns large language models by training reward models on preference data and optimizing policies to maximize predicted rewards. However, this pipeline faces two fundamental challenges: (1) reward models cannot signal when their predictions are unreliable, since they usually act as deterministic point estimators; and (2) modern group-based policy optimization can amplify unreliable reward signals, as exemplified by GRPO's uniform treatment of rewards during advantage computation. As policies explore increasingly diverse responses, these two limitations create a critical vulnerability: unreliable reward estimates may be granted disproportionate influence, triggering severe reward hacking. We propose Uncertainty-Aware Reward Modeling (UARM), which equips reward models with calibrated uncertainty via quantile-based conformal prediction and reweights GRPO advantages through heteroscedastic variance decomposition. Experiments across HelpSteer, UltraFeedback, and PKU-SafeRLHF demonstrate that UARM significantly improves reward model calibration, reduces reward hacking, and enhances downstream alignment quality compared to standard GRPO and uncertainty-agnostic baselines.

07.
arXiv (CS.CL) 2026-06-19

The Voice Behind the Words: Quantifying Intersectional Bias in SpeechLLMs

Speech Large Language Models (SpeechLLMs) process spoken input directly, retaining cues such as accent and perceived gender that were previously removed in cascaded pipelines. This introduces speaker identity dependent variation in responses. We present a large-scale intersectional evaluation of accent and gender bias in three SpeechLLMs using 2,880 controlled interactions across six English accents and two gender presentations, keeping linguistic content constant through voice cloning. Using pointwise LLM-judge ratings, pairwise comparisons, and Best-Worst Scaling with human validation, we detect recurring directional disparities. Eastern European-accented speech receives lower helpfulness scores, particularly for female-presenting voices. Responses remain polite but differ in helpfulness. While LLM judges capture the directional trend of these biases, human evaluators exhibit significantly higher sensitivity, showing stronger accent-level contrasts.

08.
arXiv (quant-ph) 2026-06-11

Isotropic random walks and Brownian diffusion on complex projective space

arXiv:2606.11438v1 Announce Type: new Abstract: We show that isotropic random walks on the complex projective space provide a canonical and analytically tractable stochastic-geometric framework for the exploration of quantum-state space. The approach combines harmonic analysis on compact rank-one symmetric spaces with stochastic pure-state evolution and yields explicit analytical expressions for transition kernels, fidelity statistics, and geometric observables associated with the Fubini–Study metric. In particular, the framework provides a solvable reference model for isotropic depolarization and Haar equilibration, reproducing Haar-random fidelity statistics and the invariant measure on projective Hilbert space without specifying a microscopic Lindblad generator. In the short-time regime, the stochastic evolution converges to Brownian diffusion generated by the Fubini–Study Laplace–Beltrami operator, while the long-time limit exhibits concentration-of-measure behaviour characteristic of high-dimensional random quantum states. We further derive analytical and asymptotic results for the first-passage-time problem, including closed-form expressions in the Brownian limit for the mean first passage time and the long-time tail of the first-passage-time distribution. For high-fidelity target states, the mean first passage time exhibits a strong dimension-dependent divergence originating from the concentration properties of the Fubini–Study geometry.

10.
bioRxiv (Bioinfo) 2026-06-10

ECMME: an atlas of selection pressures on the mammalian extracellular matrix reveals contrasting evolutionary dynamics

The extracellular matrix (ECM) is a fundamental metazoan innovation that provides structural support and regulatory cues essential for multicellular life. While core matrisome components are subject to strong functional constraints, their evolutionary dynamics at the molecular level remain incompletely characterized. Here, we present a comprehensive per-residue analysis of selection pressures across 272 human core matrisome proteins using high-quality orthologous sequences from up to 228 placental mammal species. We developed an automated pipeline integrating ortholog identification, codon-aware alignments, and site-specific selection analyses with the MEME and FUBAR methods from the HyPhy suite. Results reveal pervasive strong purifying selection across the matrisome, consistent with its structural and functional indispensability. This is accompanied by episodic positive selection and rarer pervasive positive selection, with collagens exhibiting significantly elevated episodic positive selection compared to glycoproteins and proteoglycans. To facilitate community access, we developed ECMME (ECM Molecular Evolution) browser, an intuitive open-access web resource that visualizes selection metrics plotted directly onto protein topologies. ECMME allows researchers to seamlessly browse and investigate the data, providing a powerful framework for interpreting functional sites. It is available online and requires no local installation or set-up (https://izzilab-ecmme.share.connect.posit.cloud/).

11.
arXiv (CS.AI) 2026-06-12

Token Complexity Theory for AI-Augmented Computing

作者:

arXiv:2606.12647v1 Announce Type: cross Abstract: AI-augmented computing delegates natural language queries, code generation requests, and other open-ended tasks to a cluster of AI models that processes queries and generates responses. This paradigm introduces a resource dimension that neither classical time nor space complexity captures: the cost of sending queries to and receiving responses from such a cluster. We introduce token complexity, a formal resource measure defined as the minimum expected token cost to achieve a specified level of output quality on a task, and develop a taxonomy classifying AI systems by the strength of their probabilistic properties. We develop token complexity within the framework of AI-Oracle Turing machines, in which a probabilistic Turing machine interacts with a stochastic oracle via dedicated query and response tapes. We prove basic theorems establishing that token complexity behaves as expected: monotonicity (higher quality costs more tokens), convexity (quality improvements become progressively more expensive), price sensitivity (small price changes produce bounded cost changes), and price-relativity of task ordering (the token complexity ordering of tasks can reverse depending on the query-to-response cost ratio). We prove that the complexity frontier, defined as the set of all feasible resource bounds in tokens, time, and space, is non-empty, upward-closed, and convex.

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

Pythagoras-Prover: Advancing Efficient Formal Proving via Augmented Lean Formalisation

arXiv:2606.12594v1 Announce Type: new Abstract: Modern Lean theorem provers achieve strong performance only with substantial training and inference compute, driven in part by scarce verified proof data and the long reasoning traces of formal proof search, making both supervised fine-tuning (SFT) and sampling expensive. We introduce Pythagoras-Prover, a compute-efficient open-source family of Lean theorem provers built for practical compute budgets. The family spans two generation paradigms: autoregressive models at 4B and 32B parameters, and a first proof-of-concept diffusion-based prover (4B) that iteratively refines Lean proofs at inference time. For training efficiency, we build a Lean-verified corpus stratified into easy, medium, and hard problems for curriculum SFT, so models acquire proof skills progressively from shorter, simpler proofs to longer, harder ones. During SFT, a dynamic proof-reasoning filtering scheme preserves informative proof traces while keeping each instance within an 8k-token context budget. We also introduce Augmented Lean Formalisation (ALF), which expands scarce verified corpora into variants of formal statements, populated via self-distillation for extra training signal without formally verifying every mutated instance. By perturbing known problems while preserving their formal character, ALF reduces reliance on any statement's surface form. Empirically, Pythagoras-Prover-4B surpasses DeepSeek-Prover-V2-671B at pass@32 on MiniF2F-Test (86.1% vs 82.4%) with ~167x fewer parameters, while Pythagoras-Prover-32B sets the open-source state of the art at 93.0% on MiniF2F-Test and solves 93 of 672 PutnamBench problems. We release MiniF2F-ALF, an ALF-mutated contamination-sensitive benchmark on which every evaluated model loses accuracy; here our 32B remains strongest and our 4B matches the prior state of the art, Goedel-Prover-V2-32B.

13.
medRxiv (Medicine) 2026-06-22

GCH1 p.Ser80Asn Confers Risk for Parkinson's Disease in East Asian Populations

Introduction: GCH1 has been implicated in Parkinson's disease (PD), but its risks variants and associations are not well defined. Objectives: To investigate the clinical relevance and PD risk associated with the GCH1 p.Ser80Asn variant. Methods: We first identified a segregating GCH1 p.Ser80Asn variant in a Malaysian Chinese PD family via whole genome sequencing (WGS). We assessed its risk association using multi-ancestry WGS data from the Global Parkinson's Genetics Program (GP2) (n=22,372PD vs n=8,826Controls) and meta-analysis of East Asian (EAS) cohorts (n=4,712PD vs 38,733Controls). Clinico-demographic details of affected variant carriers were collated. Results: The GCH1 p.Ser80Asn variant was enriched in GP2 EAS PD populations (n=9/2,757; 0.33%) but not detected in other ancestries. Meta-analysis revealed increased PD risk in EAS populations (odds ratio:5.1; 95%CI:2.3-10.7; p=2.89x10-5). Affected carriers (mean age at onset:56.3+-12.5 years) had additional occurrence of dystonia, while dementia was rare. Conclusions: The GCH1 p.Ser80Asn variant is a rare, EAS-enriched risk variant for PD.

14.
arXiv (CS.CL) 2026-06-16

Learning When to Sample: Confidence-Aware Selective Sampling for Efficient Chain-of-Thought Reasoning

Large language models (LLMs) can achieve strong reasoning performance through chain-of-thought (CoT) reasoning, yet they often generate unnecessarily long reasoning paths that incur high inference cost. Self-consistency-based approaches push accuracy higher still, but they require sampling and aggregating multiple reasoning trajectories, leading to substantial computational overhead. In this paper, we introduce a confidence-aware selective sampling framework that, at inference time, analyzes a single reasoning trajectory to adaptively determine whether to rely on that trajectory alone or trigger multi-path sampling. The framework uses trajectory-level numeric features and sentence-level linguistic features extracted from reasoning states to guide selective multi-path reasoning. We train it on MedQA and evaluate it in-domain on MedQA and under calibration-only transfer on MathQA, MedMCQA, and MMLU, without further fine-tuning. Experimental results show that the proposed framework maintains comparable performance to full and efficient multi-path reasoning baselines, with accuracy changes of $-0.41 \pm 0.58$ and $-0.31 \pm 0.58$ percentage points, respectively, while reducing token usage by $71.7 \pm 5.0%$ and $36.6 \pm 9.1%$. These findings demonstrate that reasoning trajectories contain rich signals for uncertainty estimation, enabling a simple, transferable mechanism to balance accuracy and efficiency in LLM reasoning.

15.
arXiv (CS.LG) 2026-06-16

AI for Social Good: An Investigation of the Causal Relationship Between Environmental Regulations and Their Effects on Air Pollution in London, UK

arXiv:2606.15257v1 Announce Type: new Abstract: Air pollution regulation is central to urban public health governance, but estimating its effects is difficult because policies are implemented non-randomly and pollution trajectories are shaped by meteorology, socioeconomic change, temporal trends, and overlapping interventions. This study develops an uncertainty-aware Bayesian deep learning framework to estimate the aggregate effect of air pollution regulations on PM$_{2.5}$ concentrations in London from 2010 to 2020. The framework integrates daily PM$_{2.5}$ observations from Inner London monitoring stations, meteorological covariates, annual socioeconomic indicators, month-of-year and day-of-week indicators, and daily regulation status data for 32 policy measures. A Bayesian LSTM captures temporal dependencies in environmental and socioeconomic covariates, Bayesian embedding layers represent temporal and regulation status inputs, and a regulation status prediction branch supports propensity score-based adjustment for non-random policy implementation. Regulatory effects are estimated by comparing observed PM$_{2.5}$ concentrations with counterfactual predictions under a hypothetical no-regulation scenario, with uncertainty summarized across repeated Bayesian training runs and bootstrap resampling. Results show that London's regulations were associated with an average PM$_{2.5}$ reduction of 1.88 $\mu$g/m$^3$, a relative reduction of 12.35%, with a 95% confidence interval of 1.64-2.12 $\mu$g/m$^3$. Estimated effects were limited before 2013, became clearer from 2013 to 2017, and were strongest in 2018 and 2019. The findings suggest that sustained and cumulative regulatory interventions contributed to measurable improvements in London's air quality. This study demonstrates how uncertainty-aware causal AI can support environmental accountability, public health protection, and evidence-based governance for environmental decision-making.

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

FronTalk: Benchmarking Front-End Development as Conversational Code Generation with Multi-Modal Feedback

We present FronTalk, a benchmark for front-end code generation that pioneers the study of a unique interaction dynamic: conversational code generation with multi-modal feedback. In front-end development, visual artifacts such as sketches, mockups and annotated creenshots are essential for conveying design intent, yet their role in multi-turn code generation remains largely unexplored. To address this gap, we focus on the front-end development task and curate FronTalk, a collection of 100 multi-turn dialogues derived from real-world websites across diverse domains such as news, finance, and art. Each turn features both a textual instruction and an equivalent visual instruction, each representing the same user intent. To comprehensively evaluate model performance, we propose a novel agent-based evaluation framework leveraging a web agent to simulate users and explore the website, and thus measuring both functional correctness and user experience. Evaluation of 20 models reveals two key challenges that are under-explored systematically in the literature: (1) a significant forgetting issue where models overwrite previously implemented features, resulting in task failures, and (2) a persistent challenge in interpreting visual feedback, especially for open-source vision-language models (VLMs). We propose a strong baseline to tackle the forgetting issue with AceCoder, a method that critiques the implementation of every past instruction using an autonomous web agent. This approach significantly reduces forgetting to nearly zero and improves the performance by up to 9.3% (56.0% to 65.3%). Overall, we aim to provide a solid foundation for future research in front-end development and the general interaction dynamics of multi-turn, multi-modal code generation. Code and data are released at https://github.com/shirley-wu/frontalk

17.
arXiv (CS.AI) 2026-06-12

Deployment-Centered Evaluation: Predicting Query-Level Rejection Risk in a Clinical LLM System

arXiv:2606.12702v1 Announce Type: new Abstract: Large language models (LLMs) are increasingly integrated into clinical systems, making it essential to evaluate the real-world utility of these systems. However, static benchmarks tend to measure correctness rather than user acceptance, aggregate performance across queries, and require densely annotated datasets – leading to major blind spots for evaluating clinical systems. In this work, we perform a deployment-centered evaluation of an LLM system embedded within electronic health records at an academic medical center, where user feedback is sparse but closely reflects the deployment conditions. Specifically, we train a pre-response classifier that estimates the risk that a future interaction will result in the user rejecting the LLM response, based on query content and deployment-specific context available before generation. We conduct a prospective analysis of our model over 4.5 months of user feedback, finding that our prediction model achieves an AUROC of 0.719. Further, we estimate the benefit of such predictions in two downstream use cases (guardrail triggering and abstention). Our key conceptual insight is that making use of deployment-specific context (i.e., the provider type, department name, language model used for response), as opposed to only query content, improves the ability to predict whether the user will reject the system output. Altogether, our empirical case study demonstrates the feasibility of predicting user rejection using deployment-specific context, opening the door to targeted guardrails.

18.
bioRxiv (Bioinfo) 2026-06-22

Reference-guided immune recovery matching prioritizes traditional Chinese medicine ingredients

Therapeutic prioritization from single-cell transcriptomes requires a target that is closer to treatment response than disease-signature reversal. In immune diseases, post-treatment recovery may follow patient- and cell-type-specific trajectories rather than a simple return along the pretreatment disease axis. We developed ImmuneNavi, a healthy-reference-anchored recovery-matching workflow for ranking traditional Chinese medicine ingredients from paired PBMC data. The workflow maps heterogeneous PBMC cohorts to a common healthy immune coordinate system, constructs patient-cell-type disease and recovery states, and processes ITCM treated-control profiles into a fixed ingredient perturbation bank. Patient and ingredient states are represented in matched gene, pathway and transcription-factor views, allowing the model to combine local transcriptional direction with more stable program-level features. A matcher trained on one paired treatment cohort preserved recovery-aligned ingredient rankings in independent PBMC cohorts without redefining the feature space, candidate set or preprocessing procedure. This provides a reusable transcriptomic pipeline for moving from paired immune-state measurements to prioritized natural-product candidates for experimental follow-up.

19.
medRxiv (Medicine) 2026-06-19

Specific epigenetic age acceleration measures are associated with oral health outcomes in U.S. adults

Objectives: Oral health conditions impact a significant proportion of the global population. Chronological age is a known risk factor; however, characterization of epigenetic age remains limited and is expected to provide additional insight into biological mechanisms. Materials and Methods: The National Health and Nutrition Examination Survey (NHANES) was used to analyze the effect of epigenetic age measures of DunedinPoAm, and epigenetic age acceleration (EAA) of Horvath, Hannum, Weidner, Lin, VidalBralo, PhenoAge, GrimAge, and GrimAge2, on various oral health outcomes from survey and examination results. Univariable and multivariable logistic regression were performed, adjusting for sex, race-ethnicity, education, poverty income ratio categories, and dental insurance coverage status. Results: DunedinPoAm was associated with the last dental appointment being for an existing issue (p=0.0093), poor general oral condition (p=0.0226), limiting food due to teeth problems (p=0.0031), and recommendation to see a dentist within the next two weeks (p=0.0171). EAAs for PhenoAge, GrimAge, and GrimAge2, were associated with a smaller number of oral health outcomes, whereas EAAs for Horvath, Hannum, Weidner, Lin, and Vidal-Bralo showed no associations. Conclusions: In a representative U.S. population, DunedinPoAm was most consistently positively associated with different adverse oral health outcomes compared with other epigenetic aging measures. Tracking specific epigenetic ages such as DunedinPoAm, EAA GrimAge, EAA GrimAge2, and PhenoAge, may aid in additional monitoring of oral health outcomes. Understanding specific aging-related CpGs associated with oral health may aid in elucidating underlying molecular mechanisms.

20.
medRxiv (Medicine) 2026-06-22

Level of Physical Activity and ApoE Status - Effects on Alzheimer's Disease and on Mortality

Background: Alzheimer's disease and related dementias (ADRD) affect over 7.2 million Americans aged 65 and older, with the APOE-4 allele representing the strongest known genetic risk factor. Physical activity (PA) has been associated with reduced dementia risk, but its interaction with APOE genotype remains poorly characterized in large, genomically informed cohorts. Methods: We conducted a retrospective cohort analysis using linked genomic, survey, and longitudinal electronic health record data from the VA Million Veteran Program (MVP). Veterans aged

21.
arXiv (CS.CV) 2026-06-17

MM++: Unsupervised Scale-Invariant Multilayer OOD Detection via Top-K Gated Feature Fusion

We introduce MM++ (Multilayer Mahalanobis++), a fully unsupervised, strictly post-hoc, and scale-invariant framework for Out-of-Distribution (OOD) detection. To address the trade-off between scale invariance and hierarchical expressivity, MM++ constructs a principled joint feature space. It first identifies discriminative intermediate layers by measuring entropy density drops, which mark the boundaries of sharp semantic compression. By fusing these selected layers with the terminal representation, the framework captures latent cross-layer correlations while mitigating early-layer noise. Crucially, a Ledoit-Wolf regularized tied covariance matrix stabilizes this unified space, enabling reliable distance estimation. Requiring no auxiliary OOD data, classifier fine-tuning, or architectural modifications, MM++ delivers robust performance across distinct architectures for both near- and far-OOD detection.

22.
arXiv (CS.AI) 2026-06-19

A Tool for the Synthesis of Adaptive Probabilistic Processors Based on the Ising Model

arXiv:2606.19533v1 Announce Type: cross Abstract: This work presents a tool for the synthesis and simulation of probabilistic architectures for solving combinatorial optimization problems by mapping them to the Ising model. The proposed approach automatically constructs the Ising Hamiltonian and determines the number of probabilistic elements (p-bits) based on problem characteristics such as size and topology. Furthermore, the tool introduces an adaptive strategy for selecting the most suitable update algorithm among Gibbs Sampling, Simulated Annealing (SA), Simulated Quantum Annealing (SQA), and cluster-based methods. Experimental results using benchmark problems demonstrate improved convergence behavior and flexibility compared to fixed approaches. The proposed framework enables systematic evaluation of probabilistic computing strategies and supports the development of future hardware implementations based on MTJs and p-bits.

23.
arXiv (quant-ph) 2026-06-17

Demonstration of Exponential Quantum Speedup with Constant-Depth Compiled Circuits for Simon's Problem

arXiv:2604.27457v2 Announce Type: replace Abstract: We demonstrate exponential algorithmic quantum speedup for a restricted-Hamming-weight version of Simon's problem, in which the hidden string $b$ is promised to satisfy $HW(b)\le w$ for a Hamming-weight cutoff $w$, on present-day superconducting quantum processors. We introduce a hardware-aware compilation strategy that reduces the quantum part of each Simon query circuit to constant depth. The resulting compiled circuits have $O(1)$ depth, require only linear nearest-neighbor connectivity, map directly onto common device layouts, and avoid additional routing and SWAP overhead. Implemented on IBM's $156$-qubit Boston and $120$-qubit Miami processors, these circuits achieve sufficient fidelity to exhibit algorithmic quantum speedup without error suppression. Using the number-of-queries-to-solution (NTS) metric, we observe exponential speedup over the classical lower-bound benchmark for all restricted-Hamming-weight cutoffs $w\ge 4$ on Boston and across low-to-intermediate Hamming-weight cutoffs on Miami; at higher Hamming-weight cutoffs on Miami, we still observe polynomial speedup. The same construction also enables unrestricted instances of Simon's problem, corresponding to $w=n$ for problem size $n$, over the finite problem-size ranges for which our NTS computation is feasible; in this regime, the observed scaling advantage is not limited to the restricted-Hamming-weight setting. These results show that careful hardware-aware compilation can make quantum speedup experimentally accessible for a canonical hidden-subgroup problem in the NISQ regime.

24.
medRxiv (Medicine) 2026-06-15

Sociodemographic Disparities in Tafamidis Initiation and Clinical Outcomes in ATTR-CM Across the United States

BACKGROUND Transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive, life-threatening disease. Sociodemographic factors may influence time to treatment initiation and resulting clinical outcomes, yet these relationships are poorly characterized. OBJECTIVE Assess the effects of sex and race on tafamidis initiation and subsequent outcomes and their interaction with factors such as ATTR-CM type and social deprivation measures. METHODS A retrospective cohort analysis was conducted using the US Komodo Healthcare Map (01/2016-06/2024) among patients with amyloidosis, identified by ICD-10-CM diagnosis codes. Cumulative incidence of treatment initiation and survival probabilities for cardiovascular-related hospitalization (CVH) or death were estimated by Kaplan-Meier, stratified by sex and race. Cox proportional hazards models were fitted for both endpoints to estimate hazard ratios, adjusting for demographics and clinical characteristics. RESULTS Of 11,311 patients identified, White and Black patients (n=9,223) were included in subsequent analyses. Within 12 months of diagnosis, White women had the lowest cumulative incidence of tafamidis initiation (11.4%), followed by Black women (22.0%), Black men (26.7%), and White men (31.0%). Event-free survival at 12 months was lowest in Black women (42.9%), followed by Black men (46.8%), White women (48.6%), and White men (54.4%). Median (95% CI) time to CVH or death was shortest for Black women (8.0 months [6.8-10.0]) followed by Black men (9.9 months [8.8-12.0]), White women (11.0 months [9.6-13.0]), and White men (15.0 months [14.0-16.0]). CONCLUSIONS In this large, real-world cohort of US patients with ATTR-CM, sex and race contributed to disparities in tafamidis initiation and survival, underscoring compounded disparities in both access and outcomes.

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

Online Shift Detection and Conformal Adaptation for Deployed Safety Classifiers

arXiv:2606.11949v1 Announce Type: new Abstract: We present an online monitoring system for distributional shift in deployed safety classifiers, using calibrated sequential statistics to detect when a classifier has moved out of distribution. Upon detection, a conformal abstention layer adapts decision thresholds to recover a target error rate epsilon=0.1. In a pre-registered factorial evaluation (4 classifiers x 5 shift conditions x 20 seeds x 2 window sizes, 800 cells), the system achieves 86.6% valid detection (693/800, 95% CI [84.1%, 88.8%]) with mean latency of 39.5 steps. Detection holds across three ground-truth regimes: synthetic onset (86.6%), real temporal jailbreaks (85%, 17/20), and GCG adversarial attacks. Weighted conformal prediction recovers up to 39 pp of lost coverage for DeBERTa (ESS=46/300) but collapses for all other classifiers (ESS~300): logistic density ratio estimation achieves perfect source/target separability in high-dimensional embedding spaces, clipping all importance weights to the floor. DeBERTa shows a gradient from effective correction (paraphrase, ESS=46) to near-total collapse (adversarial suffix, ESS=206). PCA to 32 dimensions breaks the collapse, recovering 33 pp for Llama Guard and 21 pp for ShieldGemma. Variance decomposition reveals classifier (eta^2=0.243), shift type (eta^2=0.237), and their interaction (eta^2=0.185) all contribute substantially to detection latency variance (all p