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01.
arXiv (quant-ph) 2026-06-25

Simulating Universal Quantum Gate Sets on Photonic OAM Qubits: Single-Qubit and Multi-Qubit Operations via Spatial Light Modulator Phase Holography

arXiv:2606.26088v1 Announce Type: new Abstract: Spatial light modulators (SLMs) have emerged as reconfigurable platforms for photonic quantum information processing, offering software-defined control over the orbital angular momentum (OAM) of light encoded in Laguerre-Gaussian (LG) beams. This paper presents a comprehensive simulation and hardware-grounded fidelity analysis of quantum gate operations implemented on the HOLOEYE LC 2012 transmissive SLM. A realistic three-channel noise model comprising 8-bit quantisation noise, twisted-nematic (TN) electronic and thermal noise, and phase-wrap clipping error is obtained from the manufacturer's datasheet without free-parameter fitting, yielding a total noise of $\sigma_{total} = 92.4mrad$. The complete universal single-qubit gate set $\{X, Y, Z, S, T, H\}$ and two-qubit entangling gates $\{CNOT, CZ, SWAP\}$ are simulated on a $512 \times 512$ computational grid. Results show that predicted gate fidelity are in the range of $F = 0.9914–0.9936$, with fork grating gates limited primarily by TN noise and phase gates achieving higher fidelity owing to zero phase-wrap clipping error. In addition, Bell state preparation via the H-CNOT circuit achieves $F(\Phi^+) = 0.9914$ after two SLM interactions. We benchmark our obtained results against six published experimental studies spanning the 78%–99.6% fidelity range. Finally, a wavelength-dependent analysis identifies 450–532 nm operation as the optimal regime for this device.

02.
arXiv (CS.CL) 2026-06-24

AI Fiction in the Wild

Some professional authors are beginning to use AI tools to help produce their fiction writing. Are readers using AI to generate fiction, too? Drawing on over 500,000 anonymized, English-language ChatGPT-user conversations (arXiv:2405.01470), we find that more than one third of the conversations involve some form of fiction generation – including original stories, roleplay, fanfiction, and erotica. This AI-generated fiction is notably dominated by power users. We identify common fiction generation patterns and profiles among these users, including what we call "infinite story demanders," who repeatedly request and revise variations of the same or similar narratives over extended periods of time. We show that users especially gravitate toward fanfiction and erotica, and that they are broadly drawn to generic forms, repetition, immediacy, and niche combinations of story elements. Our findings motivate two theoretical provocations. First, we argue that AI technologies may lead to a shift in the conventional relationship between the author and reader, potentially producing what we call a "solipsistic reader-writer," who both generates and consumes fiction within a closed conversational loop, interacting with a machine rather than a human other. Second, we note that LLMs enable interactivity, play, and permutation in ways that are seemingly pleasurable for users, raising questions about where AI will fit into contemporary storytelling and entertainment ecosystems. We situate these developments within broader transformations in literature and media, including self-publishing, fanfiction, and pornography, and suggest that AI-generated fiction shares structural affinities with on-demand, personalized, and repetitive cultural forms.

03.
arXiv (quant-ph) 2026-06-24

M{\o}lmer-S{\o}rensen gates in trapped-ions chains in the presence of correlated noise

arXiv:2606.23951v1 Announce Type: new Abstract: We analyze the impact of correlated laser frequency noise on M{\o}lmer-S{\o}rensen gates in qubit registers based on trapped-ion chains. Using perturbation theory, we calculate gate fidelities in the presence of noise with arbitrary power spectral density for different chain lengths and ion positions in the chain. With our approach, we account for simultaneous excitation of multiple phonon modes during gate operation. We find out that the impact of medium-frequency laser noise depends considerably on the positions of the ions in the chain. In contrast, low-frequency noise has similar effect for different chain lengths and ion positions.

04.
PLOS Medicine 2026-06-12

Comparison of count-based and clustering definitions of multimorbidity and their association with prevalence of multimorbidity, health profiles, and mortality: A cohort study of UK Biobank participants

by Gabriella C. Silva, Aurore Fayosse, Louis Jacob, Séverine Sabia, Archana Singh-Manoux, Benjamin Landré Background Multimorbidity, the presence of several chronic conditions, is linked to higher mortality and healthcare use and thus poses a major challenge for aging populations. While most studies rely on simple counts of conditions, clustering approaches have been proposed to describe patterns of co-occurring diseases. We aimed to evaluate the extent to which these methodological choices influence prevalence and association with health profiles and mortality. Methods and findings Using UK Biobank baseline data (n = 474,397), collected between 2006 and 2010, we compared six count-based definitions of multimorbidity based on different condition lists (extended, most prevalent, or body systems) and thresholds (≥2 versus ≥3 conditions). We also applied a clustering analysis to characterize subtypes of multimorbidity among participants with at least two chronic conditions. We compared prevalence and associations with concurrent health outcomes (polypharmacy, self-rated health, frailty, falls, surgery, chronic pain), blood-based measures (C-reactive protein, Cystatin-C, HDL, LDL Cholesterol, IGF-1), and 3- and 10-year mortality risks. Analyses were undertaken separately in men and women using multivariable regression models adjusted for sociodemographic characteristics and body mass index. Multimorbidity prevalence ranged from 1.0% (cluster-based) to 35.3% (count-based). Count-based definitions using lists with more conditions yielded higher prevalence. Higher thresholds identified more severe health profiles on all measured health outcomes, blood-based measures, but not higher mortality risks. Associations with blood-based measures were more pronounced using clustering, with the highest differences from the standard definition distributed across clusters. Odds ratios for 3-year mortality ranged from 1.44 [1.26; 1.64] to 4.60 [3.73; 5.62] for men and 1.35 [1.07; 1.69] to 3.83 [2.78; 5.14] for women. For 10-year mortality, they ranged from 1.42 [1.34; 1.50] to 3.86 [3.46; 4.30] in men and 1.29 [1.21; 1.39] to 3.33 [2.93; 3.77] for women, with clustering identifying groups with low prevalence and high mortality risks. Findings should be interpreted in light of the selected nature of the UK Biobank cohort and the cross-sectional assessment of several health indicators. Conclusion Operational definitions of multimorbidity substantially influence prevalence estimates, while associations with mortality appear more robust across count-based approaches. Clustering analyses provide complementary insights into heterogeneity within multimorbid populations. Future translational studies are warranted to determine how multimorbidity definitions can be optimized to ultimately improve clinical management and health outcomes in practice.

05.
arXiv (quant-ph) 2026-06-24

Connecting Quantum Tomography and Quantum Retrodiction

arXiv:2606.23777v1 Announce Type: new Abstract: Quantum tomography and quantum retrodiction are traditionally viewed as separate inference tasks: tomography reconstructs quantum states from measurement data, whereas retrodiction infers past quantum states from observed outcomes. We show that the two are manifestations of the same underlying principle. We prove that the Petz recovery map associated with a measurement channel is precisely the gradient update of the log-likelihood used in maximum-likelihood tomography. Consequently, repeated applications of the Petz map monotonically increase the likelihood. Extending beyond measurement channels, we derive a noncommutative generalization of the Petz map from the gradient of a generalized likelihood for arbitrary quantum channels. The resulting iterative procedure maximizes the likelihood and provides a general framework for quantum tomography, establishing a direct bridge between retrodiction, recovery maps, and statistical inference.

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

Reroute, Don't Remove: Recoverable Visual Token Routing for Vision-Language Models

Vision-language models (VLMs) project images into hundreds to thousands of visual tokens, making decoder inference expensive in both attention computation and KV-cache memory. Existing visual-token reduction methods largely follow a rank-and-remove paradigm: they score visual tokens, keep a compact subset, and permanently discard the rest. We show that this irreversible action is fragile because visual-token importance changes across decoder depth; tokens ranked low at one stage may become relevant in later layers, especially for grounding-sensitive queries. We propose Reroute, a training-free plug-in that replaces removal with recoverable routing. At each routing stage, selected vision tokens pass through decoder blocks, while deferred tokens bypass the stage and re-enter the candidate pool at the next routing decision. Reroute reuses existing attention-score ranking rules and stage-wise schedules, preserving the theoretical TFLOPs and KV-cache budget class of the pruning method it augments. Across FastV, PDrop, and Nüwa variants on LLaVA-1.5 and Qwen backbones, reroute improves grounding under aggressive token reduction while maintaining general VQA performance. These results suggest that VLM token reduction should not be viewed only as irreversible pruning, but also as recoverable routing. The code can be found here: https://github.com/elmma/mllm-reroute/

07.
arXiv (quant-ph) 2026-06-24

Free-Space CV-QKD with Single-Mode Fiber Reception: Effective Coupling Statistics and Protocol-Dependent Reference Noise

arXiv:2606.24431v1 Announce Type: new Abstract: We study free-space continuous-variable quantum key distribution (CV-QKD) with single-mode fiber (SMF) reception under atmospheric turbulence. The optical channel is modeled by split-step propagation through random phase screens, followed by finite-aperture collection and projection onto the guided receiving mode. We first examine the standard GG02 setting and ask which receiver-side observable is sufficient for effective key-rate prediction. We show that a mean-loss description is generally too optimistic, whereas a scalar effective law for the SMF coupling efficiency provides an accurate downstream Gaussian-channel description within the effective model considered here. We then extend the optical model to a pilot-assisted architecture in which the signal and pilot propagate through correlated but non-identical turbulent realizations generated by a frozen-flow construction. In this case, the signal coupling law alone is no longer sufficient: signal–pilot phase mismatch and loss of post-coupling coherence produce an additional protocol-dependent reference-noise penalty. The results distinguish two regimes: a scalar coupling description is largely adequate for GG02, while transmitted-reference architectures require an additional differential reference observable beyond the signal coupling statistics.

08.
arXiv (CS.CV) 2026-06-16

FrameOracle: Learning What to See and How Much to See in Videos

Vision-language models (VLMs) advance video understanding but operate under tight computational budgets, making performance dependent on selecting a small, high-quality subset of frames. Existing frame sampling strategies, such as uniform or fixed-budget selection, fail to adapt to variations in content density or task complexity. To address this, we present FrameOracle, a lightweight, plug-and-play module that predicts both (1) which frames are most relevant to a given query and (2) how many frames are needed. FrameOracle is trained via a curriculum that progresses from weak proxy signals, such as cross-modal similarity, to stronger supervision with FrameOracle-41K, the first large-scale VideoQA dataset with validated keyframe annotations specifying minimal sufficient frames per question. Extensive experiments across five VLMs and six benchmarks show that FrameOracle reduces 16-frame inputs to an average of 10.4 frames without accuracy loss. When starting from 64-frame candidates, it reduces inputs to 13.9 frames on average while improving accuracy by 1.5%, achieving state-of-the-art efficiency-accuracy trade-offs for scalable video understanding.

09.
arXiv (CS.CL) 2026-06-24

ErrorLLM: Modeling SQL Errors for Text-to-SQL Refinement

Despite the remarkable performance of large language models (LLMs) in text-to-SQL (SQL generation), correctly producing SQL queries remains challenging during initial generation. The SQL refinement task is subsequently introduced to correct syntactic and semantic errors in generated SQL queries. However, existing paradigms face two major limitations: (i) self-debugging becomes increasingly ineffective as modern LLMs rarely produce explicit execution errors that can trigger debugging signals; (ii) self-correction exhibits low detection precision due to the lack of explicit error modeling grounded in the question and schema, and suffers from severe hallucination that frequently corrupts correct SQLs. In this paper, we propose ErrorLLM, a framework that explicitly models text-to-SQL Errors within a dedicated LLM for text-to-SQL refinement. Specifically, we represent the user question and database schema as structural features, employ static detection to identify execution failures and surface mismatches, and extend ErrorLLM's semantic space with dedicated error tokens that capture categorized implicit semantic error types. Through a well-designed training strategy, we explicitly model these errors with structural representations, enabling the LLM to detect complex implicit errors by predicting dedicated error tokens. Guided by the detected errors, we perform error-guided refinement on the SQL structure by prompting LLMs. Extensive experiments demonstrate that ErrorLLM achieves the most significant improvements over backbone initial generation. Further analysis reveals that detection quality directly determines refinement effectiveness, and ErrorLLM addresses both sides by high detection F1 score while maintain refinement effectiveness.

10.
arXiv (CS.CV) 2026-06-24

TrOCR for Medieval HTR: A Systematic Ablation Study with Cross-Dataset Validation

Fine-tuning transformer-based handwritten text recognition (HTR) models on medieval manuscripts is challenging because these models are pre-trained on modern text and must adapt to a very different visual domain. This paper studies how three controllable fine-tuning choices (contrast normalization, data augmentation, and layer freezing) affect recognition accuracy when adapting TrOCR to small historical datasets. We run controlled experiments on a 13th-century Italian manuscript (I-CT 91 "Cortonese") and replicate the same experimental grid on the public READ-16 benchmark as robustness evidence. On Cortonese, our best configuration achieves 8.03% character error rate (CER). Statistical comparisons across 13 configurations show that freezing up to three encoder layers or six decoder layers does not significantly harm accuracy, while deeper freezing becomes progressively detrimental. Removing contrast normalization (CLAHE) yields 7.84% CER, comparable to a domain-specialized baseline, suggesting strong optimization can reduce reliance on image preprocessing. Cross-dataset validation on READ-16 shows that decoder freezing thresholds transfer more robustly than encoder thresholds, and combined freezing strategies require dataset-specific re-validation. Finally, we use Grad-CAM gradient attributions and decoder cross-attention maps to diagnose error patterns and failure modes revealed by the ablations. Source code is available at https://github.com/LaudareProject/TrOCR-analysis

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

StagePilot: Stage-Level Planning for Long-Horizon Dialogue Simulation in Cybergrooming

Cybergrooming is an evolving threat to youth, requiring proactive educational interventions. We address this by modeling dialogue progression as a structured planning problem over stage-wise interactions. We propose StagePilot, a dialogue framework that separates stage-level planning from response generation, in which the model selects the next stage under constrained transitions and generates responses conditioned on it, enabling coherent and realistic progression. Reinforcement learning is used to learn stage-level policies from offline data, optimizing for both emotional alignment and goal-consistent progression. Our empirical experiments show that StagePilot generates more structured, coherent dialogue trajectories and reduces conversational stagnation compared to baselines; notably, the IQL+AWAC variant reaches the final stage more often while maintaining over 70% positive or neutral responses, yielding a 43% relative improvement.

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

Generative models for decision-making under distributional shift

arXiv:2604.04342v2 Announce Type: replace Abstract: Many data-driven decision problems are formulated using a nominal distribution estimated from historical data, while performance is ultimately determined by a deployment distribution that may be shifted, context-dependent, partially observed, or stress-induced. This tutorial presents modern generative models, particularly flow- and score-based methods, as mathematical tools for constructing decision-relevant distributions. From an operations research perspective, their primary value lies not in unconstrained sample synthesis but in representing and transforming distributions through transport maps, velocity fields, score fields, and guided stochastic dynamics. We present a unified framework based on pushforward maps, continuity, Fokker-Planck equations, Wasserstein geometry, and optimization in probability space. Within this framework, generative models can be used to learn nominal uncertainty, construct stressed or least-favorable distributions for robustness, and produce conditional or posterior distributions under side information and partial observation. We also highlight representative theoretical guarantees, including forward-reverse convergence for iterative flow models, first-order minimax analysis in transport-map space, and error-transfer bounds for posterior sampling with generative priors. The tutorial provides a principled introduction to using generative models for scenario generation, robust decision-making, uncertainty quantification, and related problems under distributional shift.

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

Auditing Machine Unlearning: A Systematic Research on Whether Models Truly Forget

arXiv:2606.16110v1 Announce Type: new Abstract: Machine unlearning has been extensively studied in response to growing privacy concerns and regulatory requirements. However, auditing whether unlearning algorithms have truly erased the influence of specific data remains an open challenge. The lack of reliable and practical auditing mechanisms can lead to critical privacy risks, such as residual information leakage. This paper initiates a systematic investigation into whether existing unlearning algorithms can truly forget the designated data. We propose the first practical and general-purpose auditing framework for machine unlearning, inspired by the concept of proof of ignorance. Our framework addresses the key practicality limitations of existing methods by eliminating the need for retraining-from-scratch baselines, avoiding the training of large numbers of shadow models, and requiring no intrusive intervention in the original training process. To evaluate the effectiveness of our framework, we first conduct validation experiments to verify its soundness and completeness. We then perform comprehensive experiments across six datasets and ten representative unlearning methods. The results demonstrate that our framework reliably distinguishes between successful and failed unlearning. In particular, we observe that retraining-based and fine-tuning-based methods can achieve effective unlearning, even when the target data remain in the original dataset. In contrast, de-optimization-based methods fail to achieve true unlearning and instead degrade the model's performance. Fisher/Hessian-based methods also fail to unlearn requested data, even formal certification is provided. Moreover, we show that our framework is robust against fake unlearning attempts and generalizes well to large language models.

14.
arXiv (CS.AI) 2026-06-12

Generativism: Toward a Learning Theory for the Age of Generative Artificial Intelligence

arXiv:2606.12441v1 Announce Type: cross Abstract: The four dominant learning theories of behaviorism, cognitivism, constructivism, and connectivism show significant conceptual limitations as generative artificial intelligence (AI) proliferates in educational settings. These frameworks were formulated before the emergence of AI systems capable of generating, synthesizing, and reasoning about knowledge. This article critically examines each learning theory and identifies assumptions challenged by generative AI's affordances. Drawing on research in distributed cognition, extended mind, human-AI collaboration, AI literacy, cognitive offloading, and metacognition, the article proposes Generativism as a learning theory for the generative AI age. Generativism posits that learning increasingly occurs through the iterative co-construction of knowledge between human learners and AI systems. The proposed framework is organized around four principles: epistemic partnership, distributed agency, generative literacy, and adaptive metacognition. The framework offers a foundation for rethinking instructional design, learning, assessment, and expertise development in contexts where generative AI plays an integral role in cognition.

15.
arXiv (CS.CL) 2026-06-12

SkillChain: Closing the Loop on Skill Evolution for Image-Based E-Commerce AI Assistants

Image-based AI assistants are now deployed at production scale on e-commerce platforms, where a single uploaded image can trigger fundamentally different user intents: product search, style recommendation, visual encyclopedia, or utility tool calls, each demanding its own response format, tool invocation, and domain knowledge. Without per-intent behavioral constraints, LLM-based systems conflate these heterogeneous modes and fall short of domain quality standards, while the breadth and dynamism of the intent space render manual engineering infeasible. To address this, we present SkillChain, which closes the production feedback loop on Skill evolution, automating the lifecycle of Skills through three stages: Skill Creator for bootstrapping from task specs and trajectories, Route Optimizer for routing alignment, and Body Refiner for iterative Skill Body refinement via dual-path LLM-Judge evaluation. Deployed on a production-scale e-commerce image assistant, SkillChain substantially improves aggregate response quality, with the strongest gains on structural compliance and content quality; a one-week online A/B experiment further confirms significant gains in user engagement, content consumption, and long-term retention.

16.
Nature Medicine 2026-06-16

<b>Engineered heart muscle passes early clinical milestone</b>

Engineered heart muscle allografts derived from induced pluripotent stem cells show promising early outcomes in patients with treatment-refractory advanced heart failure with reduced left ventricular ejection fraction, in support of further clinical investigation. Engineered heart muscle allografts derived from induced pluripotent stem cells show promising early outcomes in patients with treatment-refractory advanced heart failure with reduced left ventricular ejection fraction, in support of further clinical investigation.

17.
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/).

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

ICA Lens: Interpreting Language Models Without Training Another Dictionary

Finding interpretable directions in language-model representations is critical for understanding and controlling model behavior. Sparse autoencoders (SAEs) have become the standard tool for this purpose, but using them as the default first lens often requires training, storing, and evaluating large overcomplete dictionaries. This bottleneck limits rapid exploration and raises a fundamental question: how much interpretable structure is already visible from activation geometry before training another neural dictionary? Our intuition is simple: many interpretable directions are selective on tokens, and these directions should look less Gaussian than random directions. We therefore revisit independent component analysis (ICA), a classical method for finding non-Gaussian directions, as a compact lens for language-model interpretability. We find that ICA has been underestimated for LLM interpretability, because prior uses often relied on off-the-shelf ICA implementations that are brittle on LLM activations and lacked systematic tools for inspecting and evaluating the recovered directions. To bridge these gaps, we introduce ICALens, the first practical workflow for stable, efficient, and auditable ICA analysis of LLM representations. It combines an optimized GPU-parallel FastICA pipeline with LLM-specific stability recipes and better fitting diagnostics, enabling efficient and reliable layer-wise analysis. Across GPT-2 Small, Gemma 2 2B, and Qwen 3.5 2B Base, ICALens efficiently recovers compact, human-interpretable directions without per-layer gradient-based dictionary training. On SAEBench, ICA is competitive with public SAEs in sparse probing and outperforms them in targeted probe perturbation under small-to-medium budgets. These results suggest that ICA should not be viewed as a weak baseline, but as an efficient and complementary first lens for exploring language-model representations.

19.
arXiv (quant-ph) 2026-06-15

Who can compete with quantum computers? Lecture notes on quantum inspired tensor networks computational techniques

arXiv:2601.03035v2 Announce Type: replace Abstract: This is a set of lectures on tensor networks with a strong emphasis on the core algorithms involving Matrix Product States (MPS) and Matrix Product Operators (MPO). Compared to other presentations, particular care has been given to disentangle aspects of tensor networks from the quantum many-body problem: MPO/MPS algorithms are presented as a way to deal with linear algebra on extremely (exponentially) large matrices and vectors, regardless of any particular application. The lectures include well-known algorithms to find eigenvectors of MPOs (the celebrated DMRG), solve linear problems, and recent learning algorithms that allow one to map a known function into an MPS (the Tensor Cross Interpolation, or TCI, algorithm). The lectures end with a discussion of how to represent functions and perform calculus with tensor networks using the "quantics" representation. They include the detailed analytical construction of important MPOs such as those for differentiation, indefinite integration, convolution, and the quantum Fourier transform. Three concrete applications are discussed in detail: the simulation of a quantum computer (either exactly or with compression), the simulation of a quantum annealer, and techniques to solve partial differential equations (e.g. Poisson, diffusion, or Gross-Pitaevskii) within the "quantics" representation. The lectures have been designed to be accessible to a first-year PhD student and include detailed proofs of all statements.

20.
arXiv (quant-ph) 2026-06-11

Necessary and Sufficient Conditions for Universal Gates with Pauli Strings and Beyond

arXiv:2606.12096v1 Announce Type: new Abstract: Any quantum computation consists of a sequence of unitary evolutions described by a finite set of Hamiltonians. For the case where this set consists of only products of Pauli operators, known as Pauli strings, we provide a necessary and sufficient condition for it to generate $\mathfrak{su}(2^n)$, i.e., to be universal for quantum computation on $n$ qubits. When combining Pauli strings with a general Hamiltonian, we show a sufficient (and in certain circumstances even necessary) condition for universality based on the Pauli-basis expansion of the Hamiltonian. As an application of these results, we prove two corollaries: (i) a necessary and sufficient condition for the universality of a general Hamiltonian given arbitrary single-qubit control on all qubits, and (ii) the universality of an XYZ Heisenberg Hamiltonian with local control of just two adjacent qubits.

21.
bioRxiv (Bioinfo) 2026-06-19

HTS-Oracle v2: Prospective AI-Guided Discovery and Experimental Validation of Small Molecule Modulators Across Multiple Targets

High-throughput screening (HTS) remains the cornerstone of early-phase small molecule discovery yet consistently underperforms against immunotherapy targets, yielding validated hit rates below 0.1%. Here we introduce HTS-Oracle v2, which features rigorous cross-validation that ensures honest performance estimates. HTS-Oracle v2 was trained and validated across four clinically significant immune checkpoint targets (CD28, ICOS, LAG-3, and TIGIT) achieving ROC-AUC values of 0.968, 0.969, 0.875, 0.928 respectively under rigorous cross-validation. For prospective experimental validation, HTS-Oracle v2 was applied to an 8,960-compound Enamine Protein Mimetic Library, selecting only 25 compounds per target for experimental testing using temperature-related intensity change (TRIC) technology, a 99.7% reduction in screening burden. HTS-Oracle v2 identified 4, 5, 4, and 6 validated binders from 25 prospectively selected compounds per target, corresponding to validated hit rates of 16%, 20%, 16%, and 24%, respectively. Notably, 67-80% of all experimentally confirmed hits across the full 8,960-compound library were captured within just 25 model-selected compounds per target. For CD28, this represents a 28-fold improvement over HTS-Oracle v1 (239x versus 8.4x), establishing HTS-Oracle v2 as an efficient platform for AI-guided prospective hit discovery across immunotherapy targets.

22.
medRxiv (Medicine) 2026-06-15

Shortened blastocyst vitrification achieves live birth rates comparable to standard protocols: an analysis of 3168 cryotransfers

Study question Do shortened blastocyst vitrification and warming protocols provide comparable live birth rates (LBR) and obstetrical and perinatal outcomes to traditional vitrification and warming protocols? Summary answer Shortened vitrification and warming protocols provide comparable LBR, obstetric and perinatal outcomes to traditional protocols. Shortened vitrification coupled with traditional multi step warming benefitted women >35yrs. What is known already Embryo viability following cryopreservation is dependent on blastomere survival and functional integrity, both impacted by ice crystal formation and osmotic gradients. Recent innovations in cryopreservation challenge the need for stepwise dehydration and rehydration protocols. While one step ''fast'' blastocyst warming protocols seem to provide equivalent clinical outcomes to traditional ''slow'' protocols, fewer studies investigate whether blastocyst dehydration rates can be similarly increased. A thorough safety and effectiveness evaluation remains necessary for both treatment success and offspring health. Study design, size, duration Three clinics within a network participated in this retrospective consecutive cohort study, with cycle data collected for 3603 warmed blastocysts resulting in 3168 frozen blastocyst transfers in 2170 patients between 2023 and 2025. We modelled the relationship between ''fast'' versus ''slow'' protocols and outcomes with Generalized Additive Models, and linear and logistic regressions where appropriate. Two tailed chi square with Yates correction was used to examine pregnancy loss and obstetrical and perinatal outcomes; p0.05). Importantly, women 35yrs or older at vitrification (n=1715 transfers) profited from a F/S strategy, which provided a significant increase in live birth rates (OR:1.42 [1.02-1.98] p=0.038) compared to S/S. The same improved live birth following a F/S strategy were also seen in embryos of lower quality (OR:1.78 [1.12-2.83] p=0.015), suggesting of a protective effect of this cryopreservation strategy on the developmental competence of impaired germplasm. Limitations, reasons for caution Factors affecting the results may be unaccounted for by the study retrospective nature. Wider implication of the findings Overall, shortened, ''faster'' vitrification and warming protocols provide comparable reproductive outcomes to traditional ones. The combination of shorter exposure to cryoprotectant (CPA) during vitrification and stepwise osmotic gradient during warming provided significant clinical benefits specifically to patients >35 and lower quality embryos, pointing to the possibility of adapting vitrification protocols to specific patients populations and optimizing their clinical outcomes.

23.
arXiv (CS.LG) 2026-06-15

Binary Black Hole Parameter Estimation with Hybrid CNN-Transformer Neural Networks

arXiv:2606.13941v1 Announce Type: cross Abstract: The detection of gravitational waves has revolutionized our ability to explore fundamental aspects of the Universe. Traditionally, modeled gravitational-wave signals have been identified using template-based matched filtering, followed by coincidence analysis across multiple detectors in the signal-to-noise ratio time series. Recent advances in Machine Learning and Deep Learning have sparked growing interest in their application to both signal detection and parameter estimation. In this study, a hybrid Deep Learning strategy is proposed that leverages the effectiveness of Transformer encoders alongside well-established Convolutional Neural Network architectures in an attempt to estimate the intrinsic and extrinsic parameters of non-precessing binary black hole systems. The primary focus of this work is point estimation, producing single best-fit values for each parameter rather than full posterior distributions. This method is evaluated on both simulated signals embedded in Gaussian noise and real gravitational-wave events, and it demonstrates strong predictive performance and robustness across key astrophysical parameters.

24.
arXiv (CS.LG) 2026-06-12

Robustness Verification of Recurrent Neural Networks with Abstraction Refinement

arXiv:2606.12490v1 Announce Type: new Abstract: Certified local robustness verification for recurrent neural networks (RNNs) is challenging because approximation errors introduced by nonlinear relaxations can propagate through recurrent connections and accumulate over time. As a result, scalable linear bound propagation methods often become overly conservative and fail to certify inputs that are in fact robust, especially when many pre-activation intervals cross zero. We propose an abstraction-refinement framework for RNN verification that partitions such intervals to remove the dominant relaxation error: on each refined branch, ReLU becomes exact, and smooth activations such as tanh and sigmoid admit substantially tighter linear envelopes. To control the combinatorial cost of splitting in long sequences, we introduce a SHAP-guided timestep selection strategy that ranks hidden states by their contribution to the verification objective and refines only the most critical timesteps in temporal order. Experiments on CIFAR10 and MNIST stroke benchmarks demonstrate consistent improvements in verification success and robustness-margin tightness over abstraction-only baselines, while exposing clear runtime trade-offs between ReLU and tanh models.