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01.
arXiv (quant-ph) 2026-06-12

A Quantum Algorithm for Random Number Generation

arXiv:2606.13034v1 Announce Type: new Abstract: We present a quantum algorithm for random number generation that achieves a provable quadratic speedup over classical Markov chain mixing, building on the Diaconis-Shahshahani Fourier analysis of the top-to-random card shuffle. The algorithm integrates three quantum primitives into a unified mixing circuit: the Quantum Fourier Transform (QFT), which diagonalizes the Markov transition operator; controlled phase rotations, which encode the shuffle eigenvalue spectrum; and the Grover diffusion operator, which acts as a quantum analogue of the Aldous-Diaconis strong uniform stopping time by reflecting amplitudes about their mean at each iteration. For an n-qubit register, the mixing time is O(\sqrt{n \log n}) iterations. Extending to m qudits of local dimension d reduces this to O(\sqrt{\log_d N}) iterations, where N = d^m, compared to the classical O(n \log n) bound. The qudit formulation further reduces QFT circuit depth from O(\log^2 N) to O(\log_d^2 N) gates per layer by encoding the same N-state space using m = \log_d N subsystems instead of \log_2 N qubits. We validate both variants on IBM superconducting hardware.

02.
arXiv (CS.CL) 2026-06-15

The Culture Funnel: You Can't Align What isn't in the Data

Current cultural alignment approaches focus on inference-time interventions, assuming models already contain sufficient cultural knowledge. We argue modern LLM pipelines suffer from a cultural data funnel. Using a multidimensional tagging framework across pretraining, fine-tuning, alignment, and reasoning datasets, we show explicit cultural signals decline sharply during post-training, while geographically concentrated, task-specialized data dominates. Multilinguality enhances geographic diversity of cultural knowledge but does not ensure balanced representation. Our tags improve downstream cultural benchmark performance, demonstrating that advances require shifting focus in training data pipelines. To facilitate future research, we release our culturally tagged dataset with 5.6M samples at https://huggingface.co/datasets/CohereLabs/CultureMarkers.

03.
arXiv (CS.AI) 2026-06-11

GPO: Learning from Critical Steps to Improve LLM Reasoning

arXiv:2509.16456v3 Announce Type: replace Abstract: Large language models (LLMs) are increasingly used in various domains, showing impressive potential on different tasks. Recently, reasoning LLMs have been proposed to improve the reasoning or thinking capabilities of LLMs to solve complex problems. Despite the promising results of reasoning LLMs, enhancing the multi-step reasoning capabilities of LLMs still remains a significant challenge. While existing optimization methods have advanced the LLM reasoning capabilities, they often treat reasoning trajectories as a whole, without considering the underlying critical steps within the trajectory. In this paper, we introduce Guided Pivotal Optimization (GPO), a novel fine-tuning strategy that dives into the reasoning process to enable more effective improvements. GPO first identifies the `critical step' within a reasoning trajectory - a point that the model must carefully proceed to succeed at the problem. We locate the critical step by estimating the advantage function. GPO then resets the policy to the critical step, samples the new rollout and prioritizes the learning process on those rollouts. This focus allows the model to learn more effectively from pivotal moments within the reasoning process to improve the reasoning performance. We demonstrate that GPO is a general strategy that can be integrated with various optimization methods to improve reasoning performance. Besides theoretical analysis, our experiments across challenging reasoning benchmarks show that GPO can consistently and significantly enhance the performance of existing optimization methods, showcasing its effectiveness and generalizability in improving LLM reasoning by concentrating on pivotal moments within the generation process.

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

Your Mouse and Eyes Secretly Leak Your Preference: LLM Alignment using Implicit Feedback from Users

To align a Large Language Model (LLM), most existing methods collect explicit human feedback and train a reward model to predict the human preference based on the response text. These existing methods have two key limitations. First, the users rarely provide explicit feedback for LLM responses, which makes the high-quality preference annotation expensive to collect. Second, the methods do not leverage implicit human feedback, which has proven vital to the economic moats of Internet giants. To quantify the value of implicit feedback, we build a new dataset called IFLLM, which collects 1336 multi-turn questions from the 59 Mechanical Turk workers, their mouse trajectories, and eye gazing points to the LLMs' responses from their webcams. IFLLM shows that the users have very diverse types of gazing behavior and mouse trajectories. Our reward model based on the implicit user feedback boosts the accuracy of the text-based reward model from 55% to 64% and nearly triples the relative response quality improvements after applying the DPO to eight LLMs, demonstrating the value of implicit feedback in the wild. Our data collection website, dataset, and codes can be found at https://github.com/themehulpatwari/llm-implicit-feedback/.

05.
arXiv (CS.AI) 2026-06-19

Computational Identifiability

arXiv:2606.19361v1 Announce Type: cross Abstract: Identification conditions describe the computability of a target query or parameter of interest as a function of the type and amount of information available. In causal identification, this information is often expressed in the form of a causal graph, and data are observed or collected for some subset of variables in the graph. Target queries may be for a single effect alone or for a class of effects in a given model. The derivation of an identification algorithm then defines mathematically the process by which the desired causal effect(s) can be uniquely determined, theoretically, in expectation. Identifiability in expectation, or 'theoretical identifiability,' generally assumes asymptotic properties, infinite data, or other mathematically idealized conditions. In this paper, we explore a fundamental distinction between this theoretical, idealized notion of identifiability and a proposed alternative that is computation-bound. The framework we propose - 'computational identifiability' - is to instead define a finite computational search procedure for an empirical estimator. If this process finds an estimator empirically, within a desired error tolerance, then identifiability is satisfied, conditional on the specified assumptions of the search (i.e., a prior distribution over the parameters) and conditional on the search procedure itself. Through several experiments, we demonstrate how this framework allows us to answer fine-grained, practical identification questions, such as identification with small finite samples, with ambiguous graphical criteria, with mixed observational-interventional data, and across counterfactual data and estimands. Code is available at https://github.com/lbynum/metadentify.

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

AI Engram: In Search of Memory Traces in Artificial Intelligence

arXiv:2606.14997v1 Announce Type: new Abstract: Memory formation is fundamental to intelligence, yet whether deep neural networks preserve identifiable memory traces analogous to biological memory units remains an open question. This work introduces a geometric framework to identify such "AI engrams" by formalizing the neuroscientific criteria of specificity, reactivation, sufficiency, and necessity into a constrained inverse problem. We derive a closed-form estimator that isolates individual memory traces from globally entangled parameters, and show that this biologically-derived solution corresponds to a natural gradient update on the parameter manifold. AI engrams enable surgical manipulation of learned knowledge: any subset of memories can be composed or erased through linear arithmetic, without iterative optimization. Experiments ranging from simple MLPs to LLMs demonstrate the causal validity and substantial scalability of AI engrams. Together, these results bridge theories of biological memory and artificial representation learning and offer geometric insight into how deep networks simultaneously support functional specificity within distributed storage.

07.
Nature Medicine 2026-06-11

Microglia at a key inflection point in Alzheimer’s disease

作者: 未知作者

We analyzed brains from octogenarians and cognitively resilient centenarians to understand why some individuals with substantial Alzheimer’s disease pathology develop dementia whereas others remain cognitively intact. Spatial transcriptomics revealed gene expression changes in discrete tissue domains surrounding amyloid plaques and tau pathology that distinguish early, clinically silent, disease from later stages associated with cognitive decline.

08.
arXiv (CS.LG) 2026-06-15

Can Machine Learning Forecast Rice Yields in Data-Constrained Settings? Satellite Climate Data, National Crop Statistics, and Lessons from Sierra Leone

arXiv:2606.13959v1 Announce Type: new Abstract: Sierra Leone's agriculture operates with almost no data-driven decision support, and no published machine learning study has examined the country's crop yields. We ask whether rice yield can be forecast from data Sierra Leone currently has. Using 25 years of FAOSTAT production data (2000-2024) for nine major crops, we train XGBoost, Gradient Boosting, and Random Forest under a strict anti-leakage protocol with expanding-window walk-forward evaluation across seven held-out years, benchmarked against naive persistence. No model trained on crop statistics alone outperforms persistence. Augmenting with free satellite climate data (CHIRPS rainfall, NASA POWER temperature) reverses this result: a climate-only XGBoost reduces forecast error by one third (RMSE 284 vs 428 kg/ha), a gain that holds for a linear model and is robust to excluding the anomalous 2018 season. Early-season (May-June) rainfall is the dominant predictor, implying seasonal yield risk is observable months before harvest. No model anticipated the 2018 collapse, whose origins were institutional rather than climatic. We translate the findings into policy recommendations for Sierra Leone's Feed Salone Strategy, with a fully open-source pipeline.

09.
arXiv (CS.CL) 2026-06-18

Language Models as Interfaces, Not Oracles: A Hybrid LLM-ML System for Pediatric Appendicitis

Large language models (LLMs) can make clinical decision support more accessible by interpreting free-text documentation, but their direct use as diagnostic engines is limited by sensitivity to prompts, information order, and plausible but incorrect outputs. Structured machine-learning models offer more stable risk prediction, yet they require tabular inputs that are difficult to integrate with narrative clinical workflows. We present ClaMPAPP (Clinical Language-assisted Machine-learning Pipeline for Appendicitis), a hybrid system that uses an LLM as an interface rather than as the final decision-maker. ClaMPAPP extracts schema-constrained clinical features from note-like narratives, applies deterministic plausibility checks, and passes validated features to an XGBoost classifier trained on clinical, laboratory, and ultrasound variables. We evaluated ClaMPAPP on two independent pediatric appendicitis cohorts from German hospitals and compared it with end-to-end LLM baselines, including open-source and proprietary models. To preserve ground truth while testing free-text input, narratives were generated from structured electronic health records through template rendering and constrained LLM rewriting, with additional sentence-order permutation to assess positional robustness. ClaMPAPP achieved the strongest overall diagnostic performance in both internal and external validation while minimizing missed appendicitis cases, the key safety concern in acute triage. End-to-end LLMs showed unstable sensitivity-specificity trade-offs and greater degradation under narrative reordering. These results support an LLM-as-interface, ML-as-predictor design that separates natural-language usability from predictive inference and provides a more auditable pathway for clinical decision support.

10.
arXiv (CS.CV) 2026-06-18

Taming I2V models for Image HOI Editing: A Cognitive Benchmark and Agentic Self-Correcting Framework

Current image editing methods excel at static attributes but fail at complex Human-Object Interactions (HOI), a critical challenge unaddressed by existing benchmarks that conflate HOI with static attributes, relying on global metrics incapable of simultaneously assessing dynamic interaction validity and entangled human-object pair preservation. Thus, we first introduce HOI-Edit, a comprehensive benchmark with three progressive cognitive levels, which features an automated metric HOI-Eval that reliably evaluates instance-level interaction by letting VLM Q&A after thinking with images containing grounded Human-Object pairs. Considering the task's essence of remodeling dynamic relationships, we benchmark Image-to-Video (I2V) models, finding them inherently suited for dynamic editing due to their temporal generation capabilities. Crucially, beyond superior performance, this capability provides a "replay of the failure process," offering unique diagnosability into why errors occur. We thus propose SCPE (Self-Correcting Process Editing), a novel, agentic self-correcting framework that constrains the generation of I2V models through iteratively refined prompts, enabling the generated videos to more accurately present the target HOI. Extracted frames from these videos are the final editing results. On HOI-Edit, SCPE achieves performance competitive with state-of-the-art (SOTA) editing models like Nano Banana on interaction. Code is available at https://github.com/oceanflowlab/HOI-Edit.

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

Towards an Agent-First Web: Redesigning the Web for AI Agents

arXiv:2606.19116v1 Announce Type: new Abstract: The World Wide Web was built on an assumption held for three decades: the primary consumer of web content is a human being. This permeates every layer; its access model presumes human visitors, its economics rest on human attention, and its content targets human perception. The rapid emergence of AI agents as intermediaries between humans and web content invalidates this assumption. Yet the web resists agents through blanket blocking, CAPTCHA-based exclusion, and economic models that treat agent access as extraction rather than legitimate interaction. This paper proposes a principled redesign across three layers. At the access layer, agents acting for humans should inherit equivalent access rights, governed by rate limiting and agent identification metadata in HTTP requests, analogous to browser headers, alongside a dual-layer architecture serving human-readable and agent-optimized content from the same domain. At the economic layer, we propose an intent-based tier framework grounded in the agent-as-human-proxy principle: an agent's economic obligation mirrors that of the human it represents. A token-based subscription model meters content in tokens rather than pageviews, alongside a commissioned content economy anchoring AI content production in human intentionality. At the content layer, we identify epistemic recursion, the self-referential loop in which AI-generated content is consumed by agents to produce further content, progressively detaching web knowledge from human ground truth. We propose the Agent Text Markup Language (ATML), a four-level human supervision tier model, and a cryptographic provenance chain to counter this threat. Together these constitute ten design principles for an agent-first internet, one in which agents are first-class citizens whose integration requires renegotiating the web's foundational social contract across access, economics, and content.

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

VLGA: Vision-Language-Geometry-Action Models for Autonomous Driving

Vision-language-action (VLA) models can describe scenes and reason about them in language, yet still struggle to ground their actions in the dense 3D world around them. Existing approaches either inject features from a frozen 3D foundation model without an objective that ensures the policy uses them, or constrain geometry with sparse box and map losses that provide no dense spatial signal. We introduce VLGA, the first vision-language-action model supervised to reconstruct the dense 3D world it drives through. VLGA introduces geometry as a fourth modality alongside vision, language, and action through a dedicated expert supervised by a per-pixel pointmap regression loss against LiDAR. Extensive experiments conducted on challenging nuScenes and Bench2Drive datasets for open-loop and closed-loop evaluations, respectively, show the superiority of VLGA over counterpart VLA methods. In particular, on open-loop nuScenes, VLGA sets a new state of the art among VLA methods without ego status, with the lowest L2 (0.50\,m average) and 3-second collision rate (0.18\%). On closed-loop Bench2Drive, VLGA attains the state-of-the-art driving score of 79.08, +0.71 over the strongest prior VLA, at comparable efficiency and comfort.

13.
arXiv (CS.CL) 2026-06-11

Hey Chat, Can You Teach Me? Structuring Socratic Dialogue for Human Learning in the Wild

Large language models are now widely used for everyday learning, but the underlying interactions are typically unstructured chats rather than following a curriculum. Unlike formal online learning systems, these interactions carry no prior record of the student, so any estimate of what the student already knows must be inferred from the dialogue itself. We show that this gap is not closed by scaling models alone. Frontier and education-tuned LLMs perform poorly when asked to tutor a student over an extended session, because doing so requires three things at once. The tutor must sequence a curriculum, conduct Socratic dialogue, and infer the student's knowledge state from that dialogue. We propose separating these responsibilities. Given a student query, our system constructs a prerequisite knowledge graph in which subtopics are nodes and dependencies are edges, and frames tutoring as deciding which node to teach next and how many dialogue turns to spend on it before moving on. A lightweight PPO policy handles this sequencing decision, while an LLM conducts the Socratic exchange at the chosen node and returns a signal of student progress. Across held-out STEM and non-STEM topics, our PPO-paired tutor outperforms heuristic baselines, frontier general-purpose models, and a model specialised for Socratic dialogue: on both the rate at which students reach full curriculum mastery and the number of turns required. Explicit curriculum structure delivers gains that scaling the underlying model does not.

14.
arXiv (quant-ph) 2026-06-16

Inflationary branch decoherence and the cosmological arrow of time

作者:

arXiv:2602.21263v3 Announce Type: cross Abstract: We analyze branch decoherence in inflationary quantum cosmology by computing reduced density matrices and branch-overlap factors for long-wavelength perturbations. The Hartle-Hawking no-boundary state is real in the semiclassical regime and contains both expanding and contracting WKB components, whereas the tunneling state is selected as an outgoing complex WKB branch; expanding-contracting decoherence is therefore central for the former and mainly diagnostic for the latter. Using the influence-functional formalism, we derive the noise kernel for a light spectator environment and evaluate decoherence under horizon-based and EFT-motivated coarse grainings. We then compute the single-mode branch overlap directly from the Bunch-Davies mode functions, obtaining $|\mathcal{D}_k(z)|=[z^2/(z^2+1)]^{1/4}$ in the massless limit and $|\mathcal{D}_k(z)|\sim z^\nu$ on superhorizon scales for massive fields, where $z=-k\eta$ is the dimensionless wavenumber with $\eta$ the conformal time. In the massless case, the accumulated geometric branch functional is evaluated in closed form, with a leading cutoff-sensitive phase-space term and a universal subleading contribution. The calculation provides an explicit quantitative bridge between quantum-cosmological boundary conditions, inflationary squeezing, and the emergence of effectively classical cosmological histories.

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

Information geometry and entanglement under phase-space deformation through nonsymplectic congruence transformation

arXiv:2505.02269v3 Announce Type: replace Abstract: The Fisher-Rao (FR) information matrix is a central object in multiparameter quantum estimation theory. The geometry of a quantum state can be envisaged through the Riemannian manifold generated by the FR-metric corresponding to the quantum state. Interestingly, any congruence transformation $GL(2n,\mathbb{R})$ in phase space leaves the FR-distance for Gaussian states invariant. In the present paper, we investigate whether this isometry affects the entanglement in the bipartite system. It turns out that the entanglement-generating congruent transformation depends upon the system and background space. To make our study relevant to physical systems, we choose Bopp's shift in phase space as an example of $GL(2n,\mathbb{R})$, so that the results can be interpreted in terms of noncommutative (NC) phase-space deformation. We provide an estimation of the measure of entangled states over separable states for bipartite Gaussian states under a Bopp's shift. Since the dynamics of free oscillators in background NC-space is mathematically equivalent to the dynamics of a charged particle under a homogeneous magnetic field, we provide an outline for a gedankenexperiment through photocurrent measurement in order to determine the effects of congruent transformation on the distinguishibility of Gaussian states.

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

Priors Persist Through Suppression: A Stroop Paradigm for Lexical Override

作者:

Glossaries, technical specifications, and system prompts routinely ask language models to use familiar words in unfamiliar ways. When this works, the local rule does not install the new meaning on top of the old one; the pretrained prior keeps operating underneath, and its strength still shows through. We test this with a Stroop-style paradigm: a remapping rule (doctor means forest) pitted against the query word's lexical-prior distractor (hospital), with matched neutral controls. Across 11 open-weight models spanning four families and 1B-9B parameters, lexical-prior strength predicts interference even after item-level controls for answer prior, frequency, tokenization, and prompt wording. Activation patching on five aligned models locates a source-position triplet (definition subject, definition target, query word) that nearly fully recovers the conflict effect (aggregate $R \in [0.92, 1.06]$); a definition-target swap shows the triplet performs binding rather than identity matching. Dissociation experiments isolate target preservation as the binding-specific signature: distractor suppression occurs under matched, swap, and item-mismatched conditions alike, whereas target logit collapse occurs only when the definition-target position is corrupted. Behavior and mechanism converge on the same channel: the prior's strength both predicts which overrides fail and marks where the causal repair lands.

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

The Proxy Knows Too Much: Sealing LLM API Routers with Attested TEEs

arXiv:2606.16358v1 Announce Type: cross Abstract: Agents increasingly access large language models (LLMs) through API routers. A router terminates the client's transport-layer security session and opens a separate upstream session, so it holds the full interaction in plaintext. This makes the router an application-layer man-in-the-middle: it can rewrite agent tool calls, swap dependencies for typosquatted packages, trigger attacks only under audit-evading conditions, and passively exfiltrate secrets. Existing client-side defenses are evadable. We propose AEGIS, a provider-transparent attested API router whose data path is a client-verified faithful passthrough. AEGISconfines plaintext handling to a small hardware-enclave component while leaving authentication, scheduling, accounting, and management on the untrusted host. The client verifies the enclave before releasing plaintext. The host can neither read nor alter the interaction, and plaintext leaves only toward destinations fixed by the measured image. We show that all four malicious-router attack classes succeed against a plaintext-access baseline and are blocked by AEGIS, including adaptive tests against the same boundary. The trusted path is $851$ lines, carries three provider-native APIs without conversion, and completes every request under real-provider workload and concurrency. In a seeded audit pilot, two commodity coding agents find eight and ten of ten planted invariant violations. The local relay overhead is about six milliseconds per request.

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

EPIG: Emotion-Based Prompting for Personalised Image Generation

arXiv:2606.13247v1 Announce Type: new Abstract: Text-to-image diffusion models have achieved impressive results in synthesizing high-quality images from natural language prompts. However, commonly used prompting strategies remain relatively generic, limiting the model's ability to accurately express emotional intent and nuanced affective attributes. This work proposes EPIG, a method that enhances emotional expressiveness at the prompt level prior to image generation. Grounded in psychologically informed emotion representations (valence-arousal) and leveraging structured, role-aware prompt enrichment, EPIG enriches emotion-related components of prompts without modifying or retraining the image generation backbone. The resulting emotion-aware prompts guide the generative process toward more emotionally coherent visual outputs, with particular effectiveness in controlling arousal. EPIG is lightweight, training-free, and well suited for resource-constrained and personalized image generation scenarios. Experimental results on a benchmark of 10 diverse prompts show that EPIG reduces mean arousal error compared to strong baselines, including naive insertion and LLM-based prompt expansion, with reductions of 14% and 12%, respectively. These improvements are statistically significant. EPIG also preserves valence alignment and semantic consistency, as measured by CLIPScore and supported by ablation studies. The effect is more pronounced on prompts containing explicit subjects such as humans, children, or animals, where the reduction reaches 17%, highlighting the subject-sensitive behavior of the proposed method.

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

AlignCoder: Aligning Retrieval with Target Intent for Repository-Level Code Completion

arXiv:2601.19697v2 Announce Type: replace-cross Abstract: Repository-level code completion remains a challenging task for existing code large language models (code LLMs) due to their limited understanding of repository-specific context and domain knowledge. While retrieval-augmented generation (RAG) approaches have shown promise by retrieving relevant code snippets as cross-file context, they suffer from two fundamental problems: misalignment between the query and the target code in the retrieval process, and the inability of existing retrieval methods to effectively utilize the inference information. To address these challenges, we propose AlignCoder, a repository-level code completion framework that introduces a query enhancement mechanism and a reinforcement learning based retriever training method. Our approach generates multiple candidate completions to construct an enhanced query that bridges the semantic gap between the initial query and the target code. Additionally, we employ reinforcement learning to train an AlignRetriever that learns to leverage inference information in the enhanced query for more accurate retrieval. We evaluate AlignCoder on two widely-used benchmarks (CrossCodeEval and RepoEval) across five backbone code LLMs, demonstrating an 18.1% improvement in EM score compared to baselines on the CrossCodeEval benchmark. The results show that our framework achieves superior performance and exhibits high generalizability across various code LLMs and programming languages.

20.
arXiv (CS.CL) 2026-06-18

Written by AI, Managed by AI: Semantic Space Control and Index Sickness Elimination Across 391 Consecutive Sessions

The prevailing engineering intuition for addressing conceptual drift in long-horizon LLM collaboration is to trade more formal constraints for more reliable outputs – designing symbolic identifier systems, accumulating defensive rules in System Prompts, expanding context windows. Our engineering record shows that in long-horizon settings, this direction may produce effects contrary to design intent. Using action research methods in a real software project (Bang-v3) spanning approximately one month and 391 collaborative sessions, we document and analyze the failure process of these strategies. When the symbolic system exceeds a complexity threshold, LLMs do not become more accurate – instead, they abandon genuine understanding of business semantics, retreat to self-referential reasoning within the symbolic layer, and generate outputs that appear internally consistent but are physically disconnected from reality. We name this failure pattern "Index Sickness," and its canonical manifestation "Phantom Legislation." We name the underlying principle the "Pang Principle (Semantic Vitality Law)": natural language carrying explicit purpose conveys far greater information quality than symbolic expression. From this, we design and validate its physical engineering mechanism: "Baseline-Log Physical Separation." In the same project, this mechanism reduced AI Instructions volume by ~75%, and across the subsequent ~150 sessions, no recurrence of Index Sickness was observed. A bilingual companion version (Chinese) is included as supplementary material.

21.
arXiv (quant-ph) 2026-06-12

First-order and interior-point methods for entanglement detection

arXiv:2508.05854v3 Announce Type: replace Abstract: Quantum entanglement lies at the heart of quantum information science, yet its reliable detection in high-dimensional or noisy systems remains a fundamental computational challenge. Semidefinite programming (SDP) hierarchies, such as the Doherty-Parrilo-Spedalieri (DPS) and Extension (EXT) hierarchies, offer complete methods for entanglement detection, but it is well known that their practical use is limited by exponential growth in problem size if implemented naively. We make three contributions. First, we introduce a new SDP hierarchy, PST, that is sandwiched between EXT and DP – offering a tighter approximation to the set of separable states than EXT, while incurring significantly lower computational overhead than DPS. Second, we explicitly construct compact, polynomially-scalable descriptions of EXT and PST using partition mappings and operators. These descriptions in turn yield formulations that satisfy desirable properties such as the Slater condition and are well-suited to both first-order methods (FOMs) and interior-point methods (IPMs). Third, we design a suite of entanglement detection algorithms: three FOMs (Frank-Wolfe, projected gradient, and fast projected gradient) based on a least-squares formulation, and a custom primal-dual IPM based on a conic programming formulation. These methods are numerically stable and capable of producing entanglement witnesses or proximity measures, even in cases where states lie near the boundary of separability. Numerical experiments on benchmark quantum states demonstrate that our algorithms improve the ability to solve deeper levels of the SDP hierarchy.

22.
bioRxiv (Bioinfo) 2026-06-15

Inferring Cell Fate Trajectories in Time-Resolved Metabolic RNA Labeling data

Single-cell RNA sequencing provides high-resolution snapshots of cellular states but lacks direct information about transcriptional dynamics. Metabolic RNA labeling addresses this limitation by distinguishing newly synthesized RNA, offering insight into the direction of cell state changes, and providing valuable information when attempting to recover the underlying continuous dynamics from static snapshots of cell distributions. However, existing trajectory inference methods do not fully exploit this additional signal. Here, we propose FLOWSATATE, a framework for single-cell trajectory inference that leverages time-resolved RNA labeling within an Optimal Transport setting. We model cell dynamics as a gradient flow in an inferred potential landscape parameterized by a neural network, integrating both total and labeled RNA across time points. The learned potential enables identification of key genes and transcription factors driving cell fate decisions and supports prediction of future cellular states. We benchmark our approach on its ability to generalize unseen data and recover coherent trajectories. We also apply it to study colorectal cancer response to demethylation treatment as well as neuronal differentiation of embryonic stem cells.

23.
bioRxiv (Bioinfo) 2026-06-11

Sequence-Based Therapeutic Peptide Classification with Augmented Negative Sampling

Therapeutic peptides offer high target specificity, low toxicity, and the ability to modulate protein-protein interactions, yet experimental functional characterization remains costly and slow. Computational prediction of therapeutic function directly from sequence could accelerate peptide screening and enable generative design pipelines, but requires reliable discrimination between therapeutic and non-therapeutic peptides. Existing multi-label predictors cover few functions, rely on limited datasets, and exhibit high glspl{fpr}, limiting their practical utility. We present a lightweight CNN classifier trained on the most comprehensive therapeutic peptide database to date (54,655 peptides, 48 functional categories). A key contribution is a statistically motivated negative sampling strategy using Markov models to generate diverse synthetic decoys at multiple difficulty levels. When evaluated on this controlled decoy benchmark, the FRP is reduced from over 60% for previous models to 2.1% for our approach. Our fine-tuned five-model ensemble achieves 78.9% Micro F1 and 54.6% Macro F1 while requiring only amino acid sequences as inputs. Analysis using a sparse L1-constrained variant of our model shows that convolutional filters capture conserved functional motifs and statistically improbable non-therapeutic patterns, with downstream layers combining these signals, providing mechanistic evidence that the network learns biologically meaningful structure. In a generalization task on the TPpred-LE benchmark, our model achieves 55.3% Micro F1 and 38.6% Macro F1, comparable to TPpred-LE trained on its native dataset (57.9%/38.1%) while predicting four times more therapeutic functions with four times fewer parameters. Code and models will be made available at https://github.com/terra-quantum-public/tq-therapep-ai.

24.
arXiv (quant-ph) 2026-06-17

Einstein-Podolsky-Rosen correlations between mechanical oscillators revealed through SU(1,1) interferometry

arXiv:2606.18202v1 Announce Type: new Abstract: Quantum correlations are essential for achieving quantum advantage in computing, communication and sensing. Moreover, their observation challenges and constrains our fundamental understanding of nature. Mechanical oscillators in the quantum regime provide an appealing platform for preparing and investigating quantum correlations at macroscopic scales. Despite substantial progress, however, continuous-variable quantum correlations stronger than entanglement have not yet been observed in this macroscopic regime. Here, we report the experimental observation of continuous-variable Einstein-Podolsky-Rosen correlations between two spatially-separated mechanical oscillators with an effective mass of $\sim 16 \,\mu g$ each. This is achieved by coupling them to a superconducting qubit which allows for engineering a two-mode squeezing interaction when parametrically driven. Crucially, we show that this interaction can be used to witness quantum correlations through the realization of a mechanical SU(1,1) interferometer. Our results expand the toolbox of operations in circuit quantum acoustodynamics and demonstrate that quantum correlations stronger than entanglement can also be observed in macroscopic systems, thereby shedding light on the boundary between quantum and classical regimes.

25.
Nature (Science) 2026-06-17

Towards Conversational AI for Disease Management

While large language models (LLMs) have shown promise in diagnostic dialogue1, their capabilities for effective management reasoning—including disease progression, therapeutic response, and safe medication prescription—remain under-explored. We advance the previously demonstrated diagnostic capabilities of the Articulate Medical Intelligence Explorer (AMIE)1−3 through a new LLM-based agentic system optimized for multi-visit clinical management and dialogue. To ground its reasoning in authoritative clinical knowledge, AMIE leverages Gemini’s long-context capabilities4, combining in-context retrieval with structured reasoning to align its output with up-to-date clinical practice guidelines and drug formularies. In a randomized, blinded virtual Objective Structured Clinical Examination (OSCE) study, AMIE was compared to 21 primary care physicians (PCPs) across 100 multi-visit case scenarios designed to reflect UK NICE Guidance and BMJ Best Practice guidelines. AMIE was non-inferior to PCPs in management reasoning as assessed by specialists and scored better in both preciseness of treatments and investigations, and in its alignment with and grounding in clinical guidelines. To benchmark medication reasoning, we developed RxQA, a multiple-choice question benchmark derived from two national drug formularies (US, UK) and validated by board-certified pharmacists. Though AMIE and PCPs both benefited from the ability to access external drug information, AMIE outperformed PCPs on higher difficulty questions. While further research would be needed before real-world translation, AMIE’s strong performance across evaluations marks a significant step towards conversational AI as a tool in disease management.