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01.
arXiv (CS.LG) 2026-06-16

Floating-Point Networks with Automatic Differentiation Can Represent Almost All Floating-Point Functions and Their Gradients

arXiv:2605.01702v2 Announce Type: replace Abstract: Theoretical studies show that for any differentiable function on a compact domain, there exists a neural network that approximates both the function values and gradients. However, such a result cannot be used in practice since it assumes real parameters and exact internal operations. In contrast, real implementations only use a finite subset of reals and machine operations with round-off errors. In this work, we investigate whether a similar result holds for neural networks under floating-point arithmetic, when the gradient with respect to the input is computed by the automatic differentiation algorithm $D^\mathtt{AD}$. We first show that given a floating-point function $\phi$ (e.g., a loss function), arbitrary function values and gradients can be represented by a floating-point network $f$ and $D^\mathtt{AD}(\phi\circ f)$, respectively. We further extend this result: given $\phi_1,\dots,\phi_n$, $D^\mathtt{AD}(\phi_i\circ f)$ can simultaneously represent arbitrary gradients while $f$ represents the target values, under mild conditions. Our results hold for practical activation functions, e.g., $\mathrm{ReLU}$, $\mathrm{ELU}$, $\mathrm{GeLU}$, $\mathrm{Swish}$, $\mathrm{Sigmoid}$, and $\mathrm{tanh}$.

02.
arXiv (CS.CL) 2026-06-18

Rethinking Reward Supervision: Rubric-Conditioned Self-Distillation

Post-training of reasoning language models is commonly driven by supervised distillation and reinforcement learning with verifiable rewards. Distillation often relies on chain-of-thought annotations that are expensive to obtain and may themselves be noisy, incomplete, or partially incorrect; even when the final solution is correct, an imperfect rationale can interfere with learning. Reinforcement learning with verified rewards, on the other hand, typically compresses evaluative feedback into a scalar signal, obscuring which aspects of a response should be improved. We propose Rubric-Conditioned Self-Distillation, a framework that incorporates rubrics as structured, fine-grained feedback for on-policy self-distillation. Our method conditions the teacher model on criterion-level rubrics and uses it to provide token-level guidance on the student's own sampled trajectories. This design avoids treating a single reference rationale as the sole supervision target. Instead, rubrics specify what a strong response should satisfy, enabling more fine-grained credit assignment over the reasoning process than scalar reward optimization. We instantiate this framework with a two-stage pipeline that first learns to generate task-specific rubrics and then trains a rubric-guided reasoner. We evaluate on a diverse suite of science reasoning benchmarks and results show that rubric-conditioned self-distillation effectively converts rubric-level criteria into token-level guidance over the reasoning process, surpassing GRPO by 1.0 points and OPSD by 0.9 points on average.

03.
PLOS Computational Biology 2026-06-17

Machine learning-driven identification of virulence determinants in <i>Borrelia burgdorferi</i> associated with human dissemination

by Hoa Thanh Nguyen, Catherine A. Brissette Lyme disease, the most common tick-borne infectious disease in the United States, presents with highly variable clinical outcomes, ranging from localized erythema migrans to severe disseminated complications affecting the heart, joints, and nervous system. The bacterial determinants underlying this phenotypic variation remain largely unknown, limiting our ability to predict disease progression and optimize treatment strategies. Here, we applied machine learning (ML) approaches to identify specific amino acid residues within surface-exposed virulence factors that predict human dissemination phenotypes. Utilizing the published whole genome sequences from 299 clinical Borrelia burgdorferi isolates collected from the United States and Slovenia over a 30-year period (1992–2021), we extracted and characterized translated amino acid sequences (variants) of seven known virulence factors (BB_0406, BBK32, DbpA, OspA, OspC, P66, and RevA). Protein variants were classified based on their association with disseminated versus localized infections using clinical metadata. Cramér’s V analysis revealed possible strong associations between dissemination phenotypes and five adhesins: BBK32, DbpA, OspC, P66, and RevA. We developed ML models using five algorithms with multiple feature selection strategies, achieving robust predictive performance for DbpA, OspC, and RevA variants (all performance metrics > 0.7). Feature importance analysis identified 57, 29, and 42 key predictive residues for DbpA, OspC, and RevA, respectively. Notably, B-cell epitope prediction revealed significant enrichment of ML-identified residues within predicted epitope regions for OspC (11 overlapping residues, OR = 3.57, p = 0.006) and RevA (12 overlapping residues, OR = 2.37, p = 0.048), suggesting these residues may influence immune recognition and bacterial persistence. This study establishes the first computational framework linking Borrelia protein sequence variants to clinical dissemination phenotypes, providing molecular insights into Lyme disease pathogenesis that may inform the development of improved diagnostics and therapeutic targets.

04.
arXiv (CS.CV) 2026-06-11

Understanding Cross-Sensor Feature Variations for Generalizable 3D Perception

Radar-camera BEV perception often suffers from degraded performance when evaluated across datasets, as changes in driving scenes, sensor configurations, and environmental conditions can alter both the input observations and the internal fused representations. This work studies this issue from the perspective of source-domain variation modeling, aiming to improve the robustness of BEV-based 3D detectors without relying on target-domain samples. We introduce a framework that characterizes visual scene variations in the frequency domain and uses them to synthesize diverse source-domain views. By comparing the resulting fused BEV representations, the framework further captures how image-level variations influence multi-modal BEV features. These variation patterns are then used to regularize the detector, encouraging the learned fusion space to remain stable under latent scene changes. The proposed method is applied only during training and leaves the inference pipeline unchanged. Experiments on cross-dataset radar-camera 3D detection between View-of-Delft and TJ4DRadSet demonstrate consistent improvements over multiple BEV fusion backbones, and the gains remain effective when a small amount of target-domain data is available.

05.
bioRxiv (Bioinfo) 2026-06-10

Folding the unfoldable 2: using AlphaFold and ESMFold to explore spurious proteins

Motivation: Spurious protein sequences, resulting from gene prediction errors, theoretically should not yield folded structures. AlphaFold2 was previously shown to predict short spurious sequences with high pLDDT scores and was therefore unlikely to distinguish between real proteins and spurious proteins which are usually short. We evaluate whether newer structure prediction methods (ESMFold and AlphaFold3) similarly predict short sequences with high pLDDT or if they better discriminate between spurious and real proteins. Results: All three structure prediction methods (ESMFold, AlphaFold2, and AlphaFold3) predict short spurious sequences from AntiFam with unexpectedly high pLDDT scores, however the discrimination between spurious and real proteins improves beyond 100 amino acids. By analysing sequences with disparate pTM and pLDDT scores, we identified two likely spurious shadow ORFs in Swiss-Prot and one potentially non-spurious AntiFam entry. Using the structure prediction scores, we developed a Gaussian Process Model and evaluated its performance on AlphaFold DB, identifying potential spurious proteins at scale. While limited on its own, this model can increase confidence in spurious protein identification when combined with other methods.

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

MB-Loc: Multi-planar Bird's-eye-view Localization in outdoor LiDAR scenes

Global LiDAR localization is a fundamental task for autonomous navigation systems. Recent methods perform Scene Coordinate Regression (SCR) and achieve superior accuracy over Absolute Pose Regression (APR) solutions by predicting dense 3D world coordinates. However, SCR approaches introduce two major bottlenecks: severe computational inefficiency from processing raw 3D geometries and significant performance degradation under varying sensor viewpoints. To address these limitations, we present MB-Loc, a lightweight and viewpoint-robust SCR framework. Instead of relying on heavy 3D convolutions, we project the input LiDAR scan into a 2.5D Multi-planar Bird's-Eye View (BEV) representation. By slicing the point-cloud along the Z-axis and mapping signed depths into discrete 2D planes, MB-Loc retains essential 3D geometric structures while exploiting the computational tractability of standard 2D CNNs. To handle the inherent sparsity of outdoor LiDAR, we introduce a KL-regularized latent bottleneck that explicitly models spatial uncertainty without injecting stochastic noise. Finally, to ensure rotation robustness, we apply 3D spatial augmentations prior to planar projection, forcing the network to implicitly learn viewpoint-invariant features. We perform extensive experiments on the publicly available NCLT dataset and demonstrate that our proposed method outperforms the current state-of-the-art. Operating at real-time inference speeds, MB-Loc significantly outperforms traditional 3D-SCR architectures in computational efficiency.

07.
bioRxiv (Bioinfo) 2026-06-18

Population-associated molecular variation in histologically normal breast tissue is context-dependent and associated with distinct transcriptional states

Population-associated molecular variation in breast tissue may contribute to differences in tissue biology and disease susceptibility, yet the extent to which such variation is shaped by underlying tissue states remains unclear. Here, we performed RNA-seq and lipidomic profiling of histologically normal breast tissue samples from African American (AA) and Caucasian White (CW) individuals, followed by conceptual integration of the resulting transcriptomic and lipidomic patterns. Unsupervised analysis revealed two distinct baseline transcriptional states (G1 and G2) that defined the primary axis of molecular variation across the cohort and corresponded to epithelial-enriched (G1) and vascular-enriched (G2) tissue contexts as determined by cell-type deconvolution. Global comparisons between AA and CW samples showed minimal transcriptomic differences, with only a single gene reaching significance after multiple testing correction. However, when stratified by baseline tissue state, 191 genes were differentially expressed within G1, with coordinated upregulation of extracellular matrix organization and proliferative/cytoskeletal processes in AA samples. These patterns were consistently supported across multiple enrichment approaches. No comparable population-associated differences were observed within G2. Lipidomic analyses showed partial but non-significant trends consistent with transcriptomic structure, suggesting that lipid variation provides complementary but limited support for baseline molecular differences, likely reflecting constraints of bulk tissue composition. Together, these findings suggest that population-associated molecular differences in normal breast tissue are context-dependent and emerge within specific baseline transcriptional states, where distinct biological programs can coexist and be differentially modulated. These findings highlight the importance of tissue heterogeneity in shaping molecular variation and its potential relevance to disease-associated tissue states.

08.
arXiv (CS.CL) 2026-06-19

GEMS: Geometric Constraints Enable Multi-Semantic Superposition in LLMs

作者:

Activation steering controls model behavior by modifying intermediate hidden states at inference time without retraining. Existing methods handle only single-direction injection; when multiple semantic directions are superposed without constraints, the model collapses. We show that this collapse decomposes into two independently acting sources: distributional deviation, where additive perturbations accumulate in norm across layers and drive activations outside the training distribution, and directional interference, where non-orthogonal semantic vectors mutually dampen when superposed. These two sources define the design constraints that any training-free multi-directional intervention must address. As one instantiation of these principles, we propose GEMS, a training-free method that maps each source to a corresponding geometric constraint: norm-preserving weighted superposition and targeted attention-pathway injection for distributional deviation, and real-time orthogonalization for directional interference. On GSM8K, injecting three concurrent non-mathematical directions preserves accuracy at 98% (baseline 92%), while unconstrained addition collapses to 4%; on Wikitext-2, the same injection incurs only 2.2% PPL increase. Component ablation isolates the causal role of each constraint, and layer-level probes confirm that orthogonalized signals survive the FFN pathway and reach the output distribution with semantic specificity. Qualitative steering effects transfer across architectures from 3B to 31B.

09.
arXiv (quant-ph) 2026-06-11

Time-Frequency Grid States for Reconstruction and Correction of Channel-Induced Distortion in Entangled Photons

arXiv:2606.12216v1 Announce Type: new Abstract: Characterization of time-frequency (TF) quantum states requires reliable reconstruction of their TF distributions. However, imperfect transmission or measurement channels can distort reconstructed joint spectral intensities (JSIs), especially when the underlying perturbation mechanism is unknown. Here, we experimentally demonstrate a reconstruction and correction framework that uses a TF grid state as an intrinsic frequency-domain reference. By analyzing the displacement of the grid points, a Gaussian process regression model is employed to reconstruct a correction mapping for the nonlinear coordinate deformation without assuming a prior physical model of the distortion. The learned mapping reduces the residual coordinate deviation of the TF grid state by approximately a factor of 11 and, when applied to an independent frequency-entangled test state, improves the Gaussian-shape fidelity from 76.2\% to 90.0\%. These results establish TF grid states as practical metrological resources for diagnosing and correcting distortions in TF quantum systems, providing a pathway toward distortion-resilient quantum communication and high-dimensional quantum information processing.

10.
arXiv (CS.AI) 2026-06-16

Automated ultrasound doppler angle estimation using deep learning

arXiv:2508.04243v2 Announce Type: replace-cross Abstract: Angle estimation is an important step in the Doppler ultrasound clinical workflow to measure blood velocity. It is widely recognized that incorrect angle estimation is a leading cause of error in Doppler-based blood velocity measurements. In this paper, we propose a deep learning-based approach for automated Doppler angle estimation. The approach was developed using 2100 human carotid ultrasound images including image augmentation. Five pre-trained models were used to extract images features, and these features were passed to a custom shallow network for Doppler angle estimation. Independently, measurements were obtained by a human observer reviewing the images for comparison. The mean absolute error (MAE) between the automated and manual angle estimates ranged from 3.9{\deg} to 9.4{\deg} for the models evaluated. Furthermore, the MAE for the best performing model was less than the acceptable clinical Doppler angle error threshold thus avoiding misclassification of normal velocity values as a stenosis. The results demonstrate potential for applying a deep-learning based technique for automated ultrasound Doppler angle estimation. Such a technique could potentially be implemented within the imaging software on commercial ultrasound scanners.

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

Towards End-to-End Automation of AI Research

arXiv:2606.15497v1 Announce Type: new Abstract: The automation of science is a long-standing ambition in the field of AI. While the community has made significant progress in automating individual components of the scientific process, a system that autonomously navigates the entire research lifecycle – from conception to publication – has remained out of reach. Here, we present the strongest demonstration to date toward automating the entire process end-to-end. We present The AI Scientist, which creates research ideas, writes code, runs experiments, plots and analyzes data, writes the entire scientific manuscript and performs its own peer review. Its ideas, execution, and presentation are of sufficient quality to produce a manuscript generated by an AI system that passes the first round of peer review at a major machine learning conference workshop. The workshop has an acceptance rate of 70 percent. Our system leverages modern foundation models within a complex agentic system. We evaluate The AI Scientist in two settings: a focused mode using human-provided code templates as an initial scaffold to conduct research on a specific topic, and a template-free, open-ended mode that leverages agentic search for wider scientific exploration. Both settings produce diverse ideas and automatically test, report on, and evaluate them. This achievement demonstrates AI's growing capacity for scientific contribution and signifies a potential paradigm shift in how research is conducted. As with any impactful new technology, there could be significant risks, including taxing overwhelmed review systems and adding noise to scientific literature. However, if developed responsibly, such autonomous systems could greatly accelerate scientific discovery.

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

Structured Inference with Large Language Gibbs

The knowledge encoded in large language models (LLMs) can serve as a substrate for structured reasoning over variables describing a complex world, but accessing this knowledge in a probabilistically coherent manner poses a difficult inference problem. We propose Large Language Gibbs, a scheme for structured probabilistic inference that uses conditional distributions of an LLM as transition operators. Rather than sampling structured objects through single-pass autoregressive generation, we iteratively resample individual variables conditioned on others using an LLM's next-token conditionals. This approach avoids order-dependent biases and produces a stationary distribution that reflects a compromise between all local conditionals. We apply this approach to sampling from synthetic distributions, consistent reasoning tasks, and Bayesian structure learning. The results suggest that the use of LLM conditionals in MCMC is a practical alternative to one-pass generation for structured probabilistic inference under a world prior accessible through noisy LLM conditionals.

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

Deja Vu at Scale: Paraphrase-Robust Detection of Duplicate Gherkin Steps in Behaviour-Driven Software Testing with Sentence-Transformer Embeddings and a 1.1M-Step Open Benchmark

Context. Behaviour-Driven Development (BDD) suites in Gherkin accumulate step-text duplication with documented maintenance cost. Prior detectors either require runnable tests or are single-organisation, leaving a gap: a static, paraphrase-robust, step-level detector and a public benchmark to calibrate it. Objective. We release (i) the largest cross-organisational BDD step corpus to date, (ii) a labelled pair-level calibration benchmark, and (iii) a four-strategy detector with a consolidation-savings model linking clusters to ISO/IEC 25010 maintainability sub-characteristics. Method. The corpus contains 347 public GitHub repositories, 23,667 .feature files, and 1,113,616 Gherkin steps, SPDX-tagged. The detector layers exact hashing, normalised Levenshtein, sentence-transformer cosine, and a Levenshtein-banded hybrid. Calibration uses 1,020 manually labelled step pairs under a released rubric (60-pair overlap, Fleiss kappa = 0.84). We report precision, recall, and F1 with bootstrap 95% CIs under the primary rubric and a score-free relabelling, and benchmark against SourcererCC-style and NiCad-style lexical baselines. Results. Step-weighted exact-duplicate rate is 80.2%; median-repository rate is 58.6% (Spearman rho = 0.51). The top hybrid cluster has 20,737 occurrences across 2,245 files. Near-exact reaches F1 = 0.822 on score-free labels; semantic F1 = 0.906 under the primary rubric reflects a disclosed stratification artefact. Lexical baselines reach F1 = 0.761 and 0.799. The savings model estimates 893,357 corpus-wide eliminable step occurrences; on the median repository 62.5% of step lines are eliminable.

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

How to Detect and Measure the AI Dangers to Democracy

arXiv:2606.16054v1 Announce Type: cross Abstract: Research on artificial intelligence and democracy has grown quickly over the last decade. A shared conclusion in this literature is that AI does not create new democratic problems so much as it makes old ones worse. We now see this across information ecosystems, in elections, and in public administration. However, despite growing evidence, we lack a clear way to prioritize risks in this area, compare them across domains, and identify where democratic control is most likely to break down. So, our problem is: How can we systematize the problems that AI systems pose to democratic processes? This paper argues that principal agent theory may fit the task. In many phases of democratic systems, principals delegate key functions to AI systems and their providers without really being able to monitor how these systems operate or the outputs they produce. Treating AI as a delegation problem helps identify accountability gaps and other governance failures. Most importantly, as we shall illustrate, it provides metrics for empirical assessments of AI impact on democracy. As a second analytical element, we draw on the NIST AI Risk Management Framework and its seven characteristics of trustworthy AI, which supply substantive criteria for evaluating delegated tasks. Operationalized across the three domains through measurable indicators and domain specific trustworthiness criteria, we propose an analytical framework that centers on institutional assessability as the central condition for democratic control over AI. However, we stress that how severe a harm is, and how much risk is acceptable, are evaluative judgments that current methodologies neither acknowledge nor operationalize. This becomes acute when such evaluative judgments are (silently) delegated to private vendors. We identify this as a strong limitation left for future work.

15.
PLOS Medicine 2026-05-21

Novel symptoms associated with eclampsia could improve detection and save lives

by Alice Beardmore-Gray, Andrew Shennan Eclampsia is a life-threatening complication of pre-eclampsia, yet remains difficult to predict. In this Perspective, Alice Beardmore-Gray and Andrew Shennan highlight a recent study that identifies 10 novel prodromal symptoms of eclampsia, with potential to better predict which women are at risk and therefore reduce delays in intervention.

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

Will AI Agents Free Us From Meaningless Work? A Human-Centered Analysis

arXiv:2606.12430v1 Announce Type: cross Abstract: Some claim that AI agents will free workers from the boring parts of their jobs, yet little is known about how workers themselves identify which tasks should be automated. Prior research focuses on occupations, overlooking that workers experience varying levels of meaning across tasks within the same role. We address this gap with a task-level analysis grounded in Graeber's theory of bullshit jobs. Using ratings from 202 workers on 171 workplace tasks, we (1) validate a five-item scale of perceived bullshitness, (2) show that perceived bullshitness strongly predicts desire for AI delegation, and (3) find that such tasks are also seen as requiring less human oversight. Together, these findings suggest that tasks perceived as bullshit are natural candidates for AI delegation, aligning worker preferences with perceived feasibility.

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

Improving and Evaluating Hand-Object Interaction Detection

Understanding hands and the objects they interact with, both directly and through tools, is a key step for tasks ranging from action perception to 3D reconstruction and robotics. Our paper provides several contributions to the Hand-Object Interaction (HOI) understanding literature: (1) HOI-DETR, a new framework that introduces hand-object and object-object interactions to the Co-DETR architecture to produce a state-of-the-art method; (2) a comprehensive HOI evaluation suite of 4 diverse datasets, including a video benchmark derived from the HD-EPIC dataset and fresh annotations that improve the Hands23 benchmark and (3) a trained checkpoint that significantly improves the state of the art across Hands23, HOIST, FineBio, and HD-EPIC, including mAP gains of over 20 percentage points on Hands23 and FineBio. Our ablations confirm the contributions of each model component.

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

Discovering Symmetry Groups with Flow Matching

arXiv:2512.20043v3 Announce Type: replace Abstract: Symmetry is fundamental to understanding physical systems and can improve performance and sample efficiency in machine learning. Both pursuits require knowledge of the underlying symmetries in data, yet discovering these symmetries automatically is challenging. We propose LieFlow, a novel framework that reframes symmetry discovery as a distribution learning problem on Lie groups. Instead of searching for the symmetry generators, our approach operates directly in group space, modeling a symmetry distribution over a large hypothesis group $G$. The support of the learned distribution reveals the underlying symmetry group $H \subseteq G$. Unlike previous works, LieFlow can discover both continuous and discrete symmetries within a unified framework, without assuming a fixed Lie algebra basis or a specific distribution over the group elements. Experiments on synthetic 2D and 3D point clouds, ModelNet10 and a real-world MI-Motion dataset show that LieFlow accurately discovers continuous and discrete subgroups, significantly outperforming a state-of-the-art baseline, LieGAN, in identifying discrete symmetries.

19.
arXiv (CS.LG) 2026-06-11

Attention by Synchronization in Coupled Oscillator Networks

arXiv:2606.12059v1 Announce Type: new Abstract: We address transformer attention on energy-constrained physical substrates. Softmax attention requires exponentiation and global reduction, operations with high energy cost on von Neumann hardware and no natural physical analog. We show that Kuramoto synchronization dynamics (which arise in electrical, mechanical, superconducting, and charge-density-wave oscillator arrays, among other physical systems) implement a well-defined attention operation without either. The resulting mechanism, fixed-query oscillator attention, replaces softmax's arithmetic with the equilibration of a gradient flow on the sphere: queries are learned anchors fixed on the sphere, and free oscillators evolve under Kuramoto-Lohe dynamics until they settle at positions encoding attention weights via cosine similarity. Because the computation is equilibration, it requires no exponentiation; the only global operation is an affine normalization at readout. The fixed point is provably unique and globally attractive from almost every initial condition, a guarantee that holds across every physical realization. Empirically, at the minimal hardware configuration (oscillator dimension $d_{\mathrm{osc}}$ = 2), oscillator attention outperforms softmax on keyword spotting (+1.00 pp) and on subject-verb agreement (+5.27 pp on hard sentences, with zero training failures versus one in five for softmax). On causal language modeling, where softmax retains an advantage, oscillator attention closes the gap as $d_{\mathrm{osc}}$ grows: from +11.09 PPL at $d_{\mathrm{osc}}$ = 2 to +2.98 PPL at $d_{\mathrm{osc}}$ = 32 on WikiText-2, and from +2.39 PPL at $d_{\mathrm{osc}}$ = 2 to +0.57 PPL at $d_{\mathrm{osc}}$ = 32 on TinyStories. The main objective of this work is not to replace softmax in software but to provide a mathematically grounded blueprint for accurate attention on physical substrates.

21.
bioRxiv (Bioinfo) 2026-06-18

Structure Bioinformatics of Eight Human ATP Synthase Fo Subunits and Their AlphaFold3-Predicted Water-Soluble QTY Analogs

Human mitochondrial ATP synthase is an essential rotary motor enzyme that produces most of the cellular ATP through oxidative phosphorylation. Its membrane-embedded Fo sector contains highly hydrophobic transmembrane subunits that are challenging to study in aqueous environments without detergents. This study explores whether applying the QTY code can reduce the hydrophobicity of selected ATP synthase Fo subunits while preserving their overall molecular structures. We applied the QTY code to eight human ATP synthase Fo subunits: ATP6, ATP8, ATPK, ATP68, ATPMK, AT5G1, AT5G2, and AT5G3. Hydrophobic amino acids leucine (L), isoleucine (I), valine (V), and phenylalanine (F) in transmembrane regions were systematically replaced with hydrophilic glutamine (Q), threonine (T), and tyrosine (Y). Four native subunits with available CryoEM structures from human ATP synthase (PDB: 8H9S) were superposed with their AlphaFold3-predicted QTY analogs. The native ATP synthase Fo subunits superposed well with their respective QTY analogs. For the CryoEM-native comparisons, RMSD values ranged from 0.565[A] to 2.546[A]. For the AlphaFold3-native comparisons of subunits without CryoEM structures, RMSD values ranged from 0.204[A] to 0.297[A]. Despite substantial QTY substitutions in the transmembrane regions, ranging from 38.89% to 50.79%, the QTY analogs retained similar overall folds, molecular weights, and isoelectric points. Hydrophobic surface analysis showed that the QTY analogs had reduced hydrophobic patches compared with their native counterparts, with average hydrophobicity decreasing from 0.2959 in native proteins to -1.1023 in QTY analogs. These structural bioinformatics studies suggest that the QTY code can be applied to ATP synthase Fo subunits to generate more hydrophilic, potentially water-soluble analogs while preserving overall structural similarity. These results extend the application of the QTY code to the membrane-embedded Fo sector of ATP synthase and provide a foundation for future experimental studies testing whether these QTY analogs can be expressed, purified, and evaluated for assembly or proton-transfer-related functions.

22.
bioRxiv (Bioinfo) 2026-06-15

DAQplugin: Deep Learning based Real-time Model Evaluation Plugin for ChimeraX

Although an increasing number of protein structures are determined by cryogenic electron microscopy (cryo-EM), protein structure modeling frequently suffers from residue misassignments and sequence register shifts, particularly in regions with ambiguous density. Here, we present DAQplugin, a ChimeraX plugin that performs real-time evaluation of protein models against cryo-EM density maps using the deep-learning-based residue-wise model quality (DAQ) score. Unlike existing validation tools that are typically applied after model construction, DAQplugin enables real-time deep-learning-based validation during model building and refinement. To our knowledge, DAQplugin is the first tool that provides real-time deep-learning based validation of protein models for cryo-EM map within an interactive modeling environment. In addition to identifying potential modeling errors, DAQplugin also provides guidance for correcting sequence register shifts by suggesting alternative residue placements along the backbone. The computation in this plugin is designed to run efficiently on general CPUs without requiring GPU hardware. Using DAQplugin, users can perform deep-learning-based validation on standard laptops during interactive model building, model-map fitting, and refinement. DAQplugin is able to facilitate more accurate interpretation of cryo-EM density maps and improve the reliability assessment of protein structure models.

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

Did You Forget What I Asked? Prospective Memory Failures in Large Language Models

作者:

Large language models often fail to satisfy formatting instructions when they must simultaneously perform demanding tasks. We study this behaviour through a prospective memory inspired lens from cognitive psychology, using a controlled paradigm that combines verifiable formatting constraints with benchmark tasks of increasing complexity. Across three model families and over 8,000 prompts, compliance drops by 2-21% under concurrent task load. Vulnerability is highly type-dependent: terminal constraints (requiring action at the response boundary) degrade most, with drops up to 50%, while avoidance constraints remain comparatively robust. A salience-enhanced format (explicit instruction framing plus a trailing reminder) recovers much of the lost compliance, restoring performance to 90-100% in many settings. Interference is bidirectional: formatting constraints can also reduce task accuracy, with one model's GSM8K accuracy dropping from 93% to 27%. In additional stacking experiments, joint compliance declines sharply as constraints accumulate. All results use deterministic programmatic checkers without an LLM-as-judge component on publicly available datasets.

24.
arXiv (quant-ph) 2026-06-11

Residual-Squeezing Mechanism of Mismatch in Inverse-Squeezing Kennedy Receivers

arXiv:2601.19093v4 Announce Type: replace Abstract: The discrimination of quantum states is fundamental to quantum information processing. Inverse-squeezing Kennedy (IS-Kennedy) receivers can outperform the coherent-state BPSK Helstrom benchmark at the same energy by converting transmitter-side squeezing into an effective coherent-state separation gain, without violating the Helstrom bound for the squeezed-state alphabet. This work investigates how squeezing mismatch degrades this mechanism. We show that imperfect inverse squeezing transforms the ideally nulled output into a residually squeezed state, thereby altering the photon-number statistics before detection. This residual-squeezing picture reveals a strong physical asymmetry between squeezing-magnitude and squeezing-phase mismatches. Magnitude mismatch produces an energy-independent error floor in the high-signal-energy regime, whereas phase mismatch generates a residual squeezing term that grows with signal energy. In the small-residual-squeezing regime, this leads to a polynomial growth of the leading error contribution and a rapid collapse of the SQL advantage. We also identify a parity-step effect in photon-number-resolving detection: because the nulled residual squeezed vacuum contains only even photon numbers, increasing detector resolution improves the high-energy robustness only when the effective saturation threshold crosses the next even photon number. These results identify phase locking as the dominant bottleneck for IS-Kennedy-type non-Gaussian receivers under unitary squeezing mismatch and provide design guidelines for robust squeezed-state quantum receivers.

25.
medRxiv (Medicine) 2026-06-12

Conversational Artificial Intelligence-Enabled Precision Oncology Reveals Context-Specific TGFβ and JAK/STAT Alterations in Pancreatic Cancer

Background: Pancreatic ductal adenocarcinoma (PDAC) is characterized by extensive molecular complexity, profound stromal remodeling, and limited responsiveness to systemic therapies. Although gemcitabine-based regimens remain widely utilized, the molecular pathways that influence treatment-associated biological variation are incompletely understood. The TGF{beta} and JAK/STAT signaling networks are recognized regulators of tumor progression, immune modulation, and therapeutic resistance; however, their genomic architecture in clinically stratified PDAC populations remains poorly defined. Methods: We employed a conversational artificial intelligence-driven analytical framework to investigate TGF{beta} and JAK/STAT pathway alterations in a cohort of 184 PDAC patients. Clinical and molecular data were integrated to generate age- and treatment-stratified cohorts, enabling pathway-level and gene-level analyses according to gemcitabine exposure. Findings generated through AI-assisted interrogation were subsequently evaluated using conventional statistical approaches. Results: TGF{beta} pathway alterations were identified in approximately one-quarter to one-third of tumors across clinical subgroups and demonstrated relatively stable frequencies regardless of age at diagnosis or gemcitabine treatment status. Gene-level analyses revealed that pathway disruption was predominantly driven by recurrent alterations in SMAD4, with additional low-frequency events involving TGFBR1 and TGFBR2. Notably, TGFBR2 mutations were significantly more frequent among late-onset PDAC patients receiving gemcitabine compared with untreated late-onset patients (8.8% vs. 1.4%; p = 0.04), suggesting a potential treatment-associated enrichment. In contrast, JAK/STAT pathway alterations were rare throughout the cohort, with only isolated mutations observed in pathway components including JAK1, JAK2, JAK3, STAT1, STAT3, and related regulatory genes. No significant differences in JAK/STAT alteration frequencies were identified according to age or treatment exposure. Conclusions: TGF{beta} and JAK/STAT pathways exhibit distinct genomic architectures in PDAC. TGF{beta} pathway disruption represents a recurrent feature of disease biology, largely driven by SMAD4 alterations, while TGFBR2 enrichment in gemcitabine-treated late-onset tumors suggests a potential context-specific association worthy of further investigation. Conversely, genomic alterations within the JAK/STAT pathway are uncommon, indicating that pathway activity may be regulated predominantly through non-genomic mechanisms. These findings demonstrate the utility of conversational artificial intelligence agents for rapid, scalable, and clinically contextualized pathway interrogation and support future studies integrating multi-omic data to refine precision medicine strategies in PDAC.