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

Viral Proteins Reveal Geometry of Protein Language Models

arXiv:2606.12609v1 Announce Type: new Abstract: Protein language models are trained on highly imbalanced datasets, raising the question of how they represent underrepresented biological sequences. Using viral proteins as a case study across ESM model families, we identify a dominant nativeness axis in embedding space, aligned with masked reconstruction perplexity, that orders sequences from well-modeled cellular proteins through viral proteins to shuffled and random sequences. Scaling contracts this axis unevenly across viral families. Despite this, protein language model embeddings retain viral-specific signal: viral proteins remain linearly separable beyond zero-shot perplexity and shallow sequence features. Together, these results suggest that pLM representations are structured by a general notion of nativeness while preserving information specific to distinct biological groups.

02.
medRxiv (Medicine) 2026-06-17

High burden of subclinical TB in Africa revealed from a postmortem cohort.

Tuberculosis (TB) is increasingly recognised as a spectrum of infection and disease, yet the prevalence of viable, asymptomatic Mycobacterium tuberculosis (M.tb) infection remains uncertain. Subclinical Tuberculosis (scTB), defined as microbiologically confirmed M.tb infection in the absence of recognised symptoms, is under detected by symptom, sputum and imaging-based approaches. We conducted postmortem examinations of 94 adults who died from non-infectious causes, none of whom were clinically suspected of TB or reported TB related symptoms prior to death. Lung and extrapulmonary tissues were cultured for M.tb. Viable M.tb was confirmed in six individuals, corresponding to a prevalence of 6.4% (95% CI: 2.4 to 13.4%). These findings provide direct tissue-based evidence that viable, asymptomatic M.tb infection can persist beyond the reach of conventional clinical detection. Our data suggest that a biologically active reservoir of infection may exist undetected within high-burden settings, with implications for surveillance strategies aimed at TB elimination.

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

Holo-World: Unified Camera, Object and Weather Control for Video World Model

Video world models are moving toward preserving an observed world under controllable camera and object motion while allowing its environmental state to change. Yet these controls remain isolated, and weather generation typically relies on a source video or reconstructed scene that already specifies future structure. We study a first-frame-anchored source-to-state setting, where the model starts from a single image and follows explicit camera and object controls and an optional weather instruction, then generates a video that either preserves the source world or transfers it to a target weather state. To address these challenges, we first build HoloStateData, a state video dataset that turns diverse videos into unified control samples for camera, object, and weather supervision. Second, we introduce Holo-World, a unified controllable video world model that jointly controls scene from a single image. Its Unified Scene Adapter factorizes world preservation and weather transfer into distinct parameter subspaces, using rendered background, geometry buffers, and object controls to maintain controlled scene structure while modeling weather-dependent appearance and particle effects. Additionally, Scene-Weather Decomposed CFG guides scene and weather residuals separately, strengthening target weather effects without over-amplifying the full condition. Quantitative and qualitative experiments demonstrate that Holo-World maintains precise camera and object control with consistent scene structure while transferring scenes into diverse target weather state, outperforming video-to-video weather editing baselines on weather-state generation. Our project page is available at \url{https://xiangchenyin.github.io/Holo-World/}.

04.
arXiv (CS.LG) 2026-06-18

A Neural Network Framework for Geodesic-Like Curve Computation on Parametric Surfaces

arXiv:2606.18759v1 Announce Type: cross Abstract: The concept of geodesic-like curves was introduced by Chen in 2010 as a method for estimating shortest paths (geodesics) on parametric surfaces, with its convergence established theoretically. However, an efficient numerical computational framework has not yet been developed. In this paper, we propose an elegant and efficient approach for computing geodesic-like curves by leveraging deep learning and Physics-Informed Neural Networks (PINNs). Under the proposed framework, not only can single parametric surfaces be handled efficiently, but a broad class of complex parametric surfaces including multi-surface systems with $C^0$ or higher continuity and surfaces of revolution can also be robustly addressed.

05.
arXiv (math.PR) 2026-06-18

Cramér-Type Moderate Deviations for Engel's Series via a Martingale Approach

arXiv:2606.18866v1 Announce Type: new Abstract: Let $x$ be uniformly distributed on $(0,1)$, and let $(q_n)_{n\geq1}$ be the digits of its Engel series expansion. We establish a Cramér-type moderate deviation expansion for $(\log q_n-n)/\sqrt n$. The proof is based on a martingale decomposition and asymptotic results for martingales. As consequences, we obtain a moderate deviation principle over the full range of scales between the central limit theorem and the law of large numbers, without the additional lower rate restriction required in several earlier works. We also derive a uniform Berry–Esseen bound of order $(\log n)/\sqrt n$.

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

FlowMPC: Improving Flow Matching policies with World Models

arXiv:2606.16286v1 Announce Type: cross Abstract: Flow Matching (FM) is a powerful approach for behavior cloning in multimodal action spaces [Jiang et al., 2025], but because it is not trained to directly maximize expected return, there is still room to improve how FM policies act at test time. This work investigates whether a learned world model can improve FM policies by enabling Model Predictive Path Integral (MPPI) planning over candidate action sequences proposed by the policy. Building on TD-MPC2 [Hansen et al., 2024], I introduce FlowMPC, a framework that combines an imitation-learned FM policy with a learned world model for test-time planning in ManiSkill manipulation tasks [Tao et al., 2025]. Across PickCube and PickSingleYCB, adding the world model improved performance over the FM policy alone, with especially clear gains in end-of-episode success. These results suggest that world-model-based planning can effectively complement flow-based imitation policies without modifying the FM training objective.

07.
arXiv (CS.CV) 2026-06-11

TRON: Tracing Rays to Orchestrate a Neural Renderer for 3D Gaussian Reconstructions

We introduce TRON, a rendering framework that combines 3D Gaussian ray tracing with neural rendering to enable realistic and controllable rendering of real-world 3D scenes under novel lighting, dynamic object motion, object insertion, and material editing. Prior approaches that rely solely on physically based rendering (PBR) of Gaussian representations struggle to achieve realistic relighting due to imperfections in reconstructed geometry, material estimates, and light transport estimation. At the same time, neural rendering methods often lack an explicit scene representation, limiting their ability to support interactive editing with fine-grained manipulation. TRON bridges these two paradigms. We use intrinsic decomposition priors from a learned inverse rendering model to regularize the material properties of a Gaussian field, and repurpose a ray tracer to provide radiometric guidance rather than final pixels. By treating this output as a structured 3D scaffold, we empower a lightweight neural renderer to bridge the domain gap between shading-model constrained estimates and photorealistic output. Our key insight is that the combination of explicit 3D knowledge with robust material priors provides speed and controllability, while neural rendering enables the synthesis of photorealistic images. To support real-world scenarios, we train our neural renderer with a multi-stage strategy consisting of large-scale pretraining and targeted fine-tuning on a newly constructed dataset of 2.1M rendered synthetic and real-world frames from 3D reconstructions. TRON outperforms Gaussian-based relighting methods in realism, and prior neural renderers in editability and speed. To the best of our knowledge, TRON is the first method to enable practical interactive applications in captured 3D environments, offering realistic appearance under dynamic geometric, lighting and material conditions.

08.
arXiv (CS.CL) 2026-06-17

ConSA: Controllable Sparsity in Hybrid Attention via Learnable Allocation

Hybrid architectures combining full attention (FA) and sliding-window attention (SWA) are a promising paradigm for efficient LLM inference. However, existing methods typically rely on hand-crafted rules or simple post-hoc heuristics for FA/SWA allocation and offer limited analysis of the attention behaviors underlying these designs. We propose Controllable Sparsity in Hybrid Attention (ConSA), a framework that learns optimal FA/SWA assignment under a user-specified sparsity target. ConSA employs L0 regularization to learn binary masks selecting between FA and SWA for each attention unit, while an augmented Lagrangian constraint enforces the target sparsity at either layer or KV-head granularity. We evaluate ConSA on two LLMs at the 0.6B and 1.7B scales. Learned allocations consistently outperform rule-based baselines, with KV-head-wise allocation yielding clear gains over layer-wise allocation. The learned patterns place SWA in the bottom layers and concentrate FA into contiguous middle-layer blocks, diverging from evenly interleaved patterns in rule-based methods. This structure persists across model scales, sparsity levels, and allocation granularities, revealing a fine-grained spectrum of intrinsic attention behaviors that underlies the learned allocation.

09.
arXiv (quant-ph) 2026-06-12

Invariant Measures and Weak-Magic-Injection Asymptotics in Random Monitored Quantum Circuits

arXiv:2606.13470v1 Announce Type: new Abstract: Monitored quantum circuits provide a natural setting in which scrambling, measurements, and measurement-conditioned updates compete within a stochastic many-body dynamics. From the viewpoint of nonstabilizer resource theory, this competition is especially relevant because Clifford-compatible operations preserve the stabilizer structure, while weak non-Clifford perturbations inject magic resource. Most of the existing understanding of monitored quantum circuits has been shaped by numerical simulations and phenomenological descriptions, while a rigorous dynamics theory remains less developed. In this paper, we address this gap by developing an analytical framework which lays a rigorous mathematical foundation for the study of random monitored quantum dynamics. Specifically, we study a class of monitored quantum circuits driven by random Clifford. We prove the existence and uniqueness of the stationary law, which gives an ergodic description of the long-time dynamics. We then resolve the leading asymptotics of steady magic in the weak-magic-injection limit. This tangent description makes the contrast between resource measures transparent: in odd-prime local dimension, the steady Gross–Wigner mana has a linear leading asymptotic, whereas in qubit systems the steady 2-stabilizer Rényi entropy has a quadratic leading asymptotic. These different powers reflect the distinct local geometries of the two resource measures near the stabilizer layer. In this way, this work develops an analytical framework that first establishes the stationary ergodic dynamics of random monitored quantum circuits.

10.
arXiv (CS.CL) 2026-06-15

An Empirical Study of Automating Agent Evaluation

Agent evaluation requires assessing complex multi-step behaviors involving tool use and intermediate reasoning, making it costly and expertise-intensive. A natural question arises: can frontier coding assistants reliably automate this evaluation process? Our study shows that simply prompting coding assistants is insufficient for this task. Without domain-specific evaluation knowledge, frontier coding assistants achieve only a 30% execution success rate and produce over-engineered evaluations averaging 12+ metrics per agent, indicating that strong coding ability does not automatically translate to reliable agent evaluation. We introduce EvalAgent, an AI assistant that automates the end-to-end agent evaluation pipeline. EvalAgent encodes evaluation domain expertise as evaluation skills (procedural instructions, reusable code and templates, and dynamically retrieved API documentation) that compose into a trace-based pipeline producing complete evaluation artifacts including metrics, executable code, and reports. To systematically assess generated evaluations, we introduce a meta-evaluation framework alongside AgentEvalBench, a benchmark comprising 20 agents, each paired with evaluation requirements and test scenarios. We further propose the Eval@1 metric to measure whether generated evaluation code both executes and yields meaningful results on the first run. Our experiments show that EvalAgent produces focused evaluations, improving Eval@1 from 17.5% to 65%, and achieving 79.5% human expert preference over baseline approaches. Further ablation studies show that evaluation skills are critical for handling complex evaluation: removing them causes Eval@1 to drop significantly from 65% to 30%.

11.
arXiv (quant-ph) 2026-06-19

All-valid-state HOBO encoding for constrained combinatorial optimization on NISQ devices

arXiv:2606.20017v1 Announce Type: new Abstract: Continued advancements in quantum computing have stimulated growing interest in translating quantum technologies into real-world applications. Consequently, the investigation of practically motivated NP-hard problems is of significant value. This study investigates the performance of a variational quantum eigensolver (VQE) in addressing the traveling salesperson problem (TSP) through noiseless simulations representative of noisy intermediate-scale quantum (NISQ) devices using higher-order binary optimization (HOBO) encodings. We construct a HOBO Hamiltonian with an efficient binary representation and propose an all-valid-state HOBO (AVS-HOBO) scheme based on cyclic mapping that eliminates one penalty term and reuses states that would otherwise be invalid. Using TSP instances of up to 20 cities, we compare the original HOBO and AVS-HOBO encodings from multiple perspectives, including the energy convergence behavior and the approximation, tour-length, and feasibility ratios. In addition to simulations, we perform computations on real quantum hardware with different device architectures, where we not only compare the performances of different chips but also investigate the effects of different error-mitigation methods on actual quantum machines. The results indicate that AVS-HOBO encoding enhances the practical reliability of VQE on NISQ devices and improves scalability for larger TSP instances, with broader applicability to constrained quantum optimization problems.

12.
arXiv (quant-ph) 2026-06-19

Quantum Entanglement Degree, Mean Positronium Lifetime, and the $3\gamma$/$2\gamma$ Annihilation-Rate Ratio as Novel PET Biomarkers for Hypoxia – Concept, Challenges, and Predictions

作者:

arXiv:2605.00021v3 Announce Type: replace-cross Abstract: This manuscript introduces a novel method to assess tissue oxygen concentration via the quantum entanglement (QE) of photons originating from positronium which is produced within the patient's body during positron emission tomography. We also investigate the possibility of assessing hypoxia by simultaneously detecting positronium lifetime and the positronium decay rate ratio. We introduce two distinct quantum sensing approaches. Method 1 utilizes the correlation between oxygen concentration and ortho-positronium (o-Ps) decay rates, relying on the simultaneous measurement of the mean o-Ps lifetime ($\tau_{\mathrm{oPs}}$) and the $3\gamma$-to-$2\gamma$ annihilation rate ratio of o-Ps ($R_{\mathrm{oPs-3\gamma/2\gamma}}$). Method 2 introduces a novel hypothesis: that the degree of QE is sensitive to the relative contribution of annihilation mechanisms (pick-off vs. conversion), which in turn depends on oxygen concentration. We derive a formula for partial pressure of oxygen ($p\mathrm{O}_2$) as a function of $R_{\mathrm{oPs-3\gamma/2\gamma}}$ and $\tau_{\mathrm{oPs}}$ and estimate the measurement accuracy required for these parameters - and for the degree of QE - to sense in-vivo oxygen pressure in the range between hypoxic and physoxic conditions. Theoretical models and quantitative estimates for $R_{\mathrm{oPs-3\gamma/2\gamma}}$, $\tau_{\mathrm{oPs}}$ and for the degree of QE ($C_{\mathrm{QE}}$ ) as a function of $p\mathrm{O}_2$ are provided for water, isopropanol, cyclohexane, isooctane, and adipose tissue. In particular, applying the formulas derived under the working hypothesis that in pick-off process the photons are not entangled, we estimated that for $p\mathrm{O}_2 = 0$, the degree of quantum entanglement $C_{\mathrm{QE}}$ is equal to 0.890 for adipose, 0.886 for isopropanol, 0.867 for water, 0.818 for cyclohexane, and 0.784 for isooctane.

13.
arXiv (quant-ph) 2026-06-16

Adiabatic preparation of a fractional quantum Hall fluid by coherently pumping atoms from a Bose-Einstein condensate

arXiv:2606.15951v1 Announce Type: cross Abstract: We propose a protocol to adiabatically prepare a many-particle fractional quantum Hall fluid of bosonic ultracold atoms exploiting a time-dependent coherent coupling of a strongly interacting atomic state with a large dilute Bose-Einstein condensate. Starting from an empty cloud, atoms with well-defined angular momentum are coherently pumped into the fluid by Raman beams with a Laguerre-Gauss profile. Compared to number-conserving schemes which rely on finite-size-induced topological gaps, we identify an adiabatic path in the Fock space which avoids crossing topological phase transitions and thus maintains a sizable adiabatic gap open at all times. The efficiency of our preparation protocol is numerically assessed for typical experimental parameters up to particle numbers that largely exceed the experimental state-of-the-art. The crucial advantage of including an anharmonic confinement is finally highlighted.

14.
arXiv (quant-ph) 2026-06-12

Robust Pretty Good Measurement via Hybrid Classical-Quantum Pseudoinverse Approximation and Circuit-Level Realization

arXiv:2606.13150v1 Announce Type: new Abstract: Pretty Good Measurement (PGM) is a near-optimal strategy for quantum state discrimination, but its practical realization becomes unstable when the ensemble operator is singular or ill-conditioned. We introduce a numerically robust PGM formulation based on the Moore-Penrose pseudoinverse, replacing the standard inverse square root with a threshold-regularized variant that remains well-defined across different spectral regimes. We develop a hybrid classical-quantum framework that combines pseudoinverse-based spectral preprocessing with quantum circuit realizations using block-encoding and spectral-transformation techniques. The framework incorporates support awareness, yielding physically meaningful measurement operators even in rank-deficient cases, and employs oblivious amplitude amplification to improve circuit-level success probabilities. Extensive numerical and circuit-level simulations show close agreement between theoretical predictions and quantum circuit outputs. Experiments on synthetic and real datasets, including ill-conditioned and degenerate scenarios, demonstrate stable discrimination performance where standard PGM becomes numerically unstable. The results establish a practical hybrid classical-quantum framework for robust quantum state discrimination and extend previous circuit-based implementations of the PGM testing stage toward pseudoinverse-aware measurement design.

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

PostDeg: Placement Beats Parameterization in LayerNorm GNNs

arXiv:2606.14022v1 Announce Type: new Abstract: LayerNorm-based GNNs routinely erase the topology signals (degree, centrality, $k$-core) that node-selection policies should depend on, but the literature has not located where in the residual block the erasure happens. We answer that question: a positive per-node scalar inserted before LayerNorm is divided out up to a stabilizer term, while the same scalar inserted after LayerNorm reaches the score head as representation magnitude. The surviving slot is the post-LayerNorm position. We instantiate it with PostDeg, a parameter-free post-LayerNorm inverse-degree scale, and pre-register four falsifiers (graphwise scalars, extra LayerNorm, expressive same-slot capacity, backbone-agnostic source) that would reject the rule. PostDeg gains $+3.5\%/+2.5\%/+5.6\%$ over the LN backbone on influence maximization, network dismantling, and maximum independent set, with $10/10$ paired-seed wins per task; none of the four falsifiers fires. The takeaway is that placement, not parameterization, carries the gain – a small invariance check that generalizes to any positive topology scalar in any normalized residual stack.

16.
medRxiv (Medicine) 2026-06-22

Symptom-based phenotype discovery in motor neuron disease using natural language processing of electronic health records

Background: Motor neuron disease (MND) is a fatal neurodegenerative condition with significant clinical heterogeneity that is incompletely captured by existing phenotype classifications based on onset site. Electronic health records (EHRs) contain detailed symptom documentation in clinical narratives that may enable data-driven discovery of clinically meaningful patient subgroups. Methods: We developed a natural language processing (NLP) pipeline using MedCAT to extract symptoms from clinical notes of 2,361 people with a confirmed diagnosis of MND at a tertiary neurology center. MND cohort confirmation used three complementary methods: clinic attendance records, text-based diagnosis detection, and NLP extraction with negation detection. Extracted symptoms were filtered to Unified Medical Language System semantic type T184 (Sign or Symptom) with removal of negated concepts. Patients were clustered using latent class analysis on binary symptom profiles. Survival differences were assessed using Kaplan-Meier analysis, log-rank tests, and Cox proportional hazards regression. Results: From the first clinical notes, we identified four clusters of symptoms among 872 patients and 76 symptoms: Motor-Bulbar (n=373), Motor-Tremor (n=154), Sensory-Pain (n=222), and Motor-Respiratory (n=123). When extended to all clinical notes (n=2,065; 184 symptoms), these reorganized into three clusters: Autonomic-Respiratory (n=472), Nocturnal-Respiratory (n=338), and Classic Motor (n=1,255). Survival differences were significant across all clusters in both the first notes and all notes analyses (log-rank p < 0.001). Conclusions: NLP-based symptom extraction from EHRs identifies clinically meaningful MND subgroups that extend beyond traditional onset-site classifications. Autonomic-respiratory symptom burden is associated with poorer survival while a newly identified Sensory-Pain subtype with a better prognosis. These data-driven phenotypes may improve prognostication and inform targeted supportive care.

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

DP-Hype: Federated Differentially Private Hyperparameter Search

arXiv:2510.04902v3 Announce Type: replace Abstract: Tuning hyperparameters in federated machine learning can substantially impact model performance. When hyperparameters are tuned on sensitive data, privacy becomes an important challenge and to this end, differential privacy has emerged as the de facto standard for provable privacy. A standard setting in federated learning is that clients agree on a shared setup, i.e., find a compromise from a set of hyperparameters, like a model's learning rate. Yet, prior work on privacy-preserving hyperparameter tuning is tailored to specific learning tasks, does not account for the privacy leakage of aggregated results, or offers a sub-optimal privacy-utility trade-off. In this work, we present our algorithm DP-Hype, which performs a federated and privacy-preserving hyperparameter search by conducting a federated voting based on local hyperparameter evaluations of clients. In this way, DP-Hype selects hyperparameters that lead to a compromise supported by a majority of clients, while maintaining scalability and independence from specific learning tasks. We prove that DP-Hype preserves the strong notion of differential privacy called client-level differential privacy and, importantly, show that its privacy guarantees do not depend on the number of hyperparameters. We also provide bounds on its utility guarantees, that is, the probability of finding good hyperparameters, and implement DP-Hype as a submodule in the popular Flower framework for federated machine learning. In addition, we evaluate performance on multiple benchmark data sets in iid as well as multiple non-iid settings and demonstrate high utility of DP-Hype even under small privacy budgets.

18.
arXiv (CS.CV) 2026-06-16

Show the Signal, Hide the Noise: Spectral Forcing for Pixel-Space Diffusion

Pixel-space diffusion models are trained on full-bandwidth noisy images, yet the useful signal available to the denoiser is strongly frequency dependent. Under rectified-flow diffusion and natural-image power-law spectra, the per-band data-to-noise contour $k^{*}(t) = (1-t)^{-2/\alpha}$ separates a signal-bearing low-frequency region from a noise-dominated high-frequency region at each time $t$. We show that this implicit coarse-to-fine structure is not merely descriptive: it induces a capacity-allocation problem. A standard pixel-space denoiser must discover the moving bandwidth boundary internally and can spend computation on frequency-time regions where the optimal prediction collapses to deterministic baselines rather than data-distribution modeling. To make this boundary explicit, we introduce Spectral Forcing, a parameter-free, time-conditional 2D-DCT low-pass operator applied to the noisy input before the patch embedder. Its cutoff expands monotonically with the diffusion time and becomes the identity at the data endpoint. Through controlled synthetic experiments, we identify the regime in which the operator is beneficial: coarse patch tokenization and data whose high-frequency content is predominantly noise rather than essential signal. On ImageNet-256 with JiT-700M/32, Spectral Forcing consistently improves both FID and Inception Score across different training epochs, demonstrating robust gains throughout training; at finer tokenization, the spectral forcing is still competitive. We further insert the unchanged operator into SenseNova-U1, a unified text-to-image model, where it improves DPG-Bench and GenEval, showing that the input-side spectral prior transfers beyond class-conditional generation. These results suggest a route to capacity-efficient pixel-space diffusion by showing the signal and hiding the noise.

19.
arXiv (quant-ph) 2026-06-17

Frequency upconversion of infrared signals via molecular cavity optomechanical systems with gain

arXiv:2606.17877v1 Announce Type: new Abstract: Molecular cavity optomechanical systems have recently emerged as a promising platform for enhancing infrared detection sensitivity, owing to their ability to up-convert low-frequency infrared (IR) photons to visible frequency range. Generally, under red-detuned pumping in such systems, the ideal conversion efficiency of the IR signal approaches 1. To overcome this efficiency constraint, we propose a scheme that incorporates gain into the infrared cavity of a molecular cavity optomechanical system comprising two cavities and an ensemble of N molecules. The upconversion process, which relies on IR absorption and Raman scattering associated with specific vibrational modes, is significantly amplified by the incorporation of gain under the red-detuned conditions. Moreover, our analysis demonstrates that the added noise is maintained near 0.5.

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

Quantum iterative approach to the Traveling Salesman Problem

arXiv:2606.11843v1 Announce Type: new Abstract: The Traveling Salesman Problem (TSP) is a classical NP-hard problem in combinatorial optimization, where determining the shortest route among a set of cities becomes computationally prohibitive as the problem size increases. This work explores quantum computing as an alternative approach to address this complexity. Unlike existing methods that primarily rely on quantum annealing, we propose a quantum iterative framework integrating Quantum Phase Estimation (QPE) and Grover's search algorithm. Route costs are encoded as quantum phases, enabling QPE to efficiently evaluate them, while Amplitude Amplification, implemented via the Grover-Long algorithm, iteratively refines the solution space toward the optimal route. A proof-of-concept case study on a small-scale TSP instance demonstrates the feasibility of this approach and its potential for scaling to larger optimization problems. Furthermore, under an expectation-based analysis, the algorithm exhibits an expected computational complexity of $O(\frac{m^2\log_2(m)\log_2(1/\epsilon)}{\sqrt{\epsilon}})$ which depends on the error tolerance parameter $\epsilon$. This estimation omits the initialization term, which we expect future refinements to render subdominant to Phase Estimation.

21.
arXiv (CS.AI) 2026-06-18

What Must Generalist Agents Remember?

arXiv:2606.18746v1 Announce Type: new Abstract: This paper develops a formal account of what generalist agents must store in memory in order to act near-optimally across multiple environments and goals. It shows that when two domains share an observational bottleneck but require incompatible optimal actions, any uniformly near-optimal policy must induce distinct memory distributions at that bottleneck. The result yields a separation theorem: sufficiently successful agents cannot rely only on current state observations, but must preserve domain-relevant information in memory. The paper further shows that if an agent's memory contains enough information to estimate values for related goals, then that memory can be used to approximately reconstruct the agent's local transition dynamics. Together, these results characterize memory as the substrate that supports domain disambiguation, transition-model reconstruction, and planning for generalist agents.

23.
bioRxiv (Bioinfo) 2026-06-12

From Proteome Mining to Structural Validation: Phosphopyruvate Hydratase as a Structurally Tractable Drug Target in Kinetoplastid Parasites

Chagas disease, caused by Trypanosoma cruzi, demands novel therapeutic strategies that overcome the toxicity and limited efficacy of current treatments. To address this need, herein we report an integrative, target-centric strategy that combines parasite proteome mining, structural modeling, and experimental validation. Functional enrichment and druggability analyses identified phosphopyruvate hydratase (PPH) as a promising candidate due to its essential metabolic role and limited similarity to human homologs. Notably, proteome mining revealed the presence and conservation of PPH across kinetoplastid parasites, including Leishmania donovani, supporting its evaluation beyond T. cruzi. For the selected PPH sequences, AlphaFold-derived three-dimensional models underwent extensive molecular dynamics refinement, yielding stable conformational ensembles suitable for structure-based studies. Using this validated model, virtual screening of the Latin American Natural Products Database - LANaPDB - identified aptosimon as a top-ranked compound candidate. Molecular dynamics simulations further showed ligand-dependent binding behavior, suggesting alternative binding modes distinct from the canonical substrate configuration. In vitro assays demonstrated consistent antiparasitic activity against intracellular T. cruzi amastigotes (IC50 = 3.52 ug/mL) and Leishmania donovani promastigotes (IC50 = 13.06 ug/mL), supporting the biological relevance of the aptosimon-related lignan chemotype, hinokinin, across two kinetoplastid parasite models. Together, these results support PPH as a structurally tractable and biologically relevant candidate target, while identifying an aptosimon-related lignan chemotype, represented experimentally by hinokinin, as a cross-species antiparasitic scaffold that warrants further biochemical target-validation studies.

24.
arXiv (CS.CL) 2026-06-18

Mitigating Scoring Errors and Compensating for Nonverbal Subtests in Speech-Based Dementia Assessment

Early detection of cognitive impairment relies on neuropsychological tests to minimize subjectivity by assessing multiple cognitive domains. Speech-based evaluation can support diagnostics and improve accessibility, but transcription errors and the omission of nonverbal subtests (e.g., motor skills) limit accuracy. Beyond conventional test scores, speech-derived features can provide additional insights into cognitive status. This study investigates the speech-based evaluation of the German "Syndrom-Kurz-Test," a standardized dementia screening test comprising verbal and motor subtests. We train models that integrate transcript-derived scores and Whisper embeddings per verbal subtest to reduce scoring errors. To compensate for missing motor subtests, we then leverage these fused representations to approximate expert overall ratings. Despite omitting subtests, our models strongly correlate with expert ratings and efficiently and accurately discriminate between cognitive status groups.

25.
medRxiv (Medicine) 2026-06-18

Cost analysis of overseas versus domestic vaccination of US-bound refugees

Context: To ensure healthy resettlement and protect US health security, the Vaccination Program for US-bound Refugees (VPR) offers some recommended vaccines to refugees overseas before resettlement to the United States. The selected vaccines and number of doses vary by country of departure. VPR was found to be cost-saving in 2018 but had since expanded to more sites. Objective: Assess VPR's current costs and impact on post-arrival domestic vaccination needs and costs. Setting and Participants: A model-based analysis of the Federal government costs for VPR and post-arrival (US) vaccination of resettled refugees separated across five regions: Africa, Asia, the Middle East and North Africa/Republic of Turkiye and Middle East, Europe, and the Americas using fiscal year 2024 data. Design: We quantified and compared full vaccination costs for refugees under two scenarios: (1) 'No VPR' and (2) 'VPR'. Refugees would receive no vaccines overseas and be fully vaccinated after US arrival under 'No VPR'. Under 'VPR', refugees receive one or two doses of selected vaccines overseas before completing vaccination schedules after arrival. Main Outcomes: Costs were reported in 2023 US dollars for 'VPR' and 'No VPR' scenarios and further subdivided by grouping countries/sites depending on whether the International Organization for Migration (IOM) provides vaccination services for refugees (IOM sites) versus non-IOM providers (non-IOM sites). Results: 'VPR' resulted in average net cost savings of $147 per person or $14.7 million per 100,000-refugee cohort compared to providing all vaccines after US arrival ('No VPR'). 'VPR' was cost-saving across most regions, except for IOM sites in Europe, where a net cost of $44 per person was observed. Net cost savings per person were highest for IOM sites in Africa ($333). Conclusions: VPR remains a cost-saving strategy, while protecting US-bound refugees' health and US health security by preventing disease outbreaks during resettlement.