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01.
arXiv (quant-ph) 2026-06-19

Simulation of Non-Markovian Quantum Accelerated Dynamics via Time-Fractional Schrödinger Equation

arXiv:2606.20024v1 Announce Type: new Abstract: The Time-Fractional Schrödinger Equation (TFSE) is an effective tool for simulating the dynamics of non-Markovian quantum systems. The Quantum Speed Limit (QSL) time characterizes the minimum time required for the evolution of a non-Markovian quantum system. In this paper, Wei's TFSE is employed to simulate the non-Markovian quantum accelerated evolution process in the Resonant Dissipative Jaynes-Cummings (RDJC) model. By solving the QSL time of a time-fractional single-qubit open system, the enhancement mechanism of the system evolution speed induced by the non-Markovian memory effects of the environment is revealed. Further studies show that the optimized acceleration of the system evolution can be achieved by jointly regulating the fractional order, coupling strength, and photon number. Comparative analyses indicate that Wei's TFSE can accurately capture the non-Markovian accelerated dynamical features of the system over the entire fractional order range, whereas Naber's TFSE is applicable only within a limited fractional order interval. In addition, the comparisons of the average simulation time for calculating the dynamical trajectory of the excited-state probability demonstrate that Wei's TFSE has a significant simulation advantage in computational efficiency. Therefore, Wei's TFSE is more accurate and efficient for simulating the accelerated dynamics of non-Markovian quantum systems.

02.
medRxiv (Medicine) 2026-06-17

Low-Density Lipoprotein Cholesterol and Dementia Risk: Integrating Mendelian Randomization and Target Trial Emulation Within the Heart-Brain Axis

Background: The heart-brain axis links cardiovascular and neurodegenerative disease through shared vascular and inflammatory mechanisms. Although low-density lipoprotein cholesterol (LDL-C) is an established causal factor in atherosclerotic cardiovascular disease (ASCVD), its relationship with dementia remains uncertain, with midlife elevations associated with increased risk but late-life associations often appearing null or inverse. To address this cholesterol paradox, we integrated mendelian randomization (MR) with an active-comparator new-user target trial emulation. Methods: We applied a triangulated causal inference framework integrating two-sample MR with observational target trial emulation. Genetic variants associated with LDL-C were used as instrumental variables to evaluate Alzheimer disease (AD), dementia with Lewy bodies (DLB), frontotemporal dementia (FTD), and any dementia (AnyDem), with causal estimates derived using inverse-variance weighted models and sensitivity analyses for heterogeneity and pleiotropy. In parallel, an active-comparator new-user design compared statin versus ezetimibe initiation among adults aged 60 years or older using propensity score (PS) overlap weighting and Cox proportional hazards models to evaluate cardiovascular and dementia outcomes. Results: Genetically predicted LDL-C was associated with increased risk of DLB (OR 1.65, 95% CI 1.30-2.10; p

03.
medRxiv (Medicine) 2026-06-24

Biochemical fingerprinting of human scalp hair reveals endocannabinoid related compounds as potential biomarker indicators of altered mitochondrial bioenergetics in immune cells from female patients with major depressive disorder

Major depressive disorder (MDD) is a severe psychiatric disorder that affects more than 350 million people worldwide, yet its biomolecular mechanisms are incompletely understood, and clinically applicable markers remain elusive. To shed new light on the underlying pathophysiology of MDD across multiple research disciplines, we first used a biochemical fingerprinting approach with human hair (the first 3 cm cut from the scalp) to identify changes in the total set of detectable metabolites and lipids (metabolipidomics) using quadrupole time-of-flight mass spectrometry (qToF-MS). In this study, we focused on endocannabinoid (ECB)-related lipid compounds and identified 7 candidate markers that differed between depressed and non-depressed female participants. Two phosphatidylinositols, namely PI 24:0 and PI 37:4, showed dose-dependent associations with the severity of depressive symptoms. Finally, to bridge hair findings with previously reported results in blood, we tested associations between changes in identified ECB-related compounds and parameters of mitochondrial respiratory activity in peripheral blood mononuclear cells. We found 17 significant associations, with the strongest effects for the lipids PI 24:0, MGDG-O 16:3, PG 12:0, and PI 37:4. Our approach not only identified novel associations between endocannabinoid (ECB)-related lipid dysregulation and impaired mitochondrial energy metabolism in MDD but also revealed ECB-related lipids as a possible surrogate marker of impaired bioenergetic metabolism in MDD, at least in immune cells. More research is needed to replicate these findings, ideally by testing reversibility in longitudinal intervention studies and by including both sexes in larger cohorts.

04.
arXiv (CS.CV) 2026-06-25

PhyGile: Physics-Prefix Guided Motion Generation for Agile General Humanoid Motion Tracking

Humanoid robots are expected to execute agile and expressive whole-body motions in real-world settings. Existing text-to-motion generation models are predominantly trained on captured human motion datasets, whose priors assume human biomechanics, actuation, mass distribution, and contact strategies. When such motions are directly retargeted to humanoid robots, the resulting trajectories may satisfy geometric constraints (e.g., joint limits and pose continuity) and appear kinematically reasonable. However, they frequently violate the physical feasibility required for real-world execution. To address these issues, we present PhyGile, a unified framework that closes the loop between robot-native motion generation and General Motion Tracking (GMT). PhyGile performs physics-prefix-guided robot-native motion generation at inference time, directly generating robot-native motions in a 262-dimensional skeletal space with physics-guided prefixes, thereby eliminating inference-time retargeting artifacts and reducing generation-execution discrepancies. Before physics-prefix adaptation, we train the GMT controller with a curriculum-based mixture-of-experts scheme, followed by post-training on unlabeled motion data to improve robustness over large-scale robot motions. During physics-prefix adaptation, the GMT controller is further fine-tuned with generated objectives under physics-derived prefixes, enabling agile and stable execution of complex motions on real robots. Extensive offline and real-robot experiments demonstrate that PhyGile expands the frontier of text-driven humanoid control, enabling stable tracking of agile, highly difficult whole-body motions that go well beyond walking and low-dynamic motions typically achieved by prior methods.

05.
arXiv (CS.CV) 2026-06-25

V-Zero: Answer-Label-Free On-Policy Distillation with Contrastive Evidence Gating for Fine-Grained Visual Reasoning

Fine-grained visual reasoning requires multimodal large language models (MLLMs) to identify task-relevant visual evidence and ground their reasoning in local image regions. Existing agentic methods typically rely on reinforcement learning with verifiable rewards or supervised fine-tuning on large-scale annotated reasoning traces, leading to costly exploration, hand-designed verification rules, or heavy dependence on textual supervision. A natural way to avoid such external answer labels is to learn from trajectories sampled by the student itself, which points to On-Policy Distillation (OPD). To understand what OPD can and cannot provide for visual reasoning, we revisit it as negative-free stop-gradient alignment. This perspective shows that, although OPD provides effective token-level correction, its ceiling is constrained by the absence of trajectory-level discrimination. Motivated by these observations, we propose V-Zero, an answer-label-free framework for visual reasoning with contrastive evidence gating. V-Zero uses no annotated textual answer labels; instead, during training it pairs a question-relevant regional crop with a negative visual view to evaluate student-sampled trajectories and gate dense token-level distillation. Experiments on multiple visual reasoning benchmarks show that V-Zero consistently improves fine-grained visual reasoning while preserving strong generalization. Notably, V-Zero is more than 5$\times$ faster than previous supervised fine-tuning methods and more than 10$\times$ faster than reinforcement learning baselines. Code and dataset will be released at https://github.com/eVI-group-SCU/V-Zero

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

Learning What to Remember: A Cognitively Grounded Multi-Factor Value Model for Agentic Memory

arXiv:2606.12945v1 Announce Type: new Abstract: Long-running LLM agents accumulate interaction histories far larger than any context window, forcing a standing decision: what to encode deeply, what to forget, and what to retrieve under a fixed memory budget. Production systems answer with semantic similarity or recency – both mis-specified for the forgetting decision, which is made at consolidation time before the future query is known. We propose a multi-factor memory value function V(m)=\sum_i w_i f_i(m) over seven interpretable factors (emotional intensity, goal relevance, value alignment, self/user relevance, task utility, reliability, and usage history) drawn from cognitive psychology, whose weights are learned from a downstream objective by a gradient-free optimiser, and whose single scalar uniformly controls encoding depth, forget risk, and retrieval rank. We make a methodological point: on LongMemEval, scoring goal relevance against the held-out evaluation question saturates gold-evidence retention at \approx 0.98 – this measures retrieval, not forgetting. In the realistic blind regime, a learned multi-factor value retains 0.770 \pm 0.011 of gold evidence across 479 usable cases, versus 0.657 for uniform weights, 0.518 for the best single factor, and 0.368 for recency; every paired gap's 95% bootstrap CI is above zero, and a neural network over the same factors ties the linear model. The learned weights are interpretable – reliability, emotional intensity, and self/user relevance dominate, while query-time goal similarity is correctly down-weighted for the forgetting decision. A controlled synthetic task with planted confounds confirms the learner recovers a separating weighting (1.00 retention) where uniform weighting fails (0.62). The substrate is open-source; all experiments run on a single CPU with no API calls.

07.
arXiv (CS.AI) 2026-06-12

Functional Cache Grafting: Robust and Rapid Code-Policy Synthesis for Embodied Agents

arXiv:2606.13097v1 Announce Type: cross Abstract: Code-writing large language models (CodeLLMs) generate executable code policies for embodied agents by translating natural language goals and environmental constraints into structured control programs. However, policy generation in open-domain embodied environments suffers from two fundamental limitations: (i) delayed decoding caused by repetitive prefill computation over long prompts, and (ii) limited robustness due to fully generative decoding, which often produces API mismatches, missing safety guards, and unstable control logic. To address these limitations, we present FCGraft, a Functional Cache Grafting framework. FCGraft maintains a library of function-level validated code skeletons and their associated prompt-level Transformer key-value (KV) caches, and synthesizes new policies by retrieving relevant functions and grafting their KV caches when a new task is provided. Given retrieved function caches, FCGraft performs cache grafting via stitching, which composes cached function segments into a composite policy, and patching, which locally adapts only the necessary code regions to satisfy task-specific parameters and constraints with minimal additional decoding. By eliminating redundant prefill computation, this approach reduces generation latency, while reusing validated control structures improves robustness over prompt-level caching methods RAGCache, achieving 18.31% higher task success rate and 2.3x faster policy synthesis.

08.
arXiv (CS.CL) 2026-06-12

GENEB: Why Genomic Models Are Hard to Compare

Progress in genomic foundation models is difficult to assess due to fragmented benchmarks, incompatible evaluation protocols, and task-specific reporting. As a result, claims of superiority or generality across models are often not directly comparable. We introduce GENEB, a large-scale diagnostic benchmark that evaluates frozen representations from 40 genomic foundation models across 100 tasks spanning 13 functional categories under a unified probing-based protocol, including few-shot regimes. GENEB enables controlled comparison across model scale, architecture, tokenization, and pretraining data while explicitly exposing task-level trade-offs. Our analysis shows that aggregate leaderboards are unstable: model rankings vary sharply across task categories, scale provides only modest and inconsistent gains, and architectural and pretraining alignment frequently outweigh parameter count. These results highlight limitations of current evaluation practices and position GENEB as a reference framework for principled comparison and category-aware model selection in genomic machine learning.

09.
arXiv (CS.CL) 2026-06-19

Efficiently Representing Algorithms With Chain-of-Thought Transformers

The increasing popularity of reasoning models – language models that output a series of reasoning or thought tokens before producing an answer – is justified, in part, by theoretical results showing that chain-of-thought (CoT) transformers can simulate Turing machines, and thus perform arbitrary computation. However, the Turing machine, while suitable for complexity-theoretic analysis, is not convenient, intuitive, or efficient for discussing algorithms. Algorithms are typically designed and analyzed at a higher level of abstraction, captured by the Word RAM model with random-access memory and unit-cost operations on $\bigO(\log n)$-bit words. As a result, Word RAM algorithms can be substantially more efficient than their Turing machine counterparts, raising the question: Can CoT transformers efficiently simulate Word RAM algorithms? For instance, can they sort $n$ items in $\bigO(n \log n)$ steps or run Dijkstra's algorithm in $\bigO(E + V \log V)$ steps? We answer affirmatively, up to poly-logarithmic overhead. We first establish this for finite-precision transformers with poly-logarithmic width and rightmost unique hard attention, then strengthen the result to two more practical settings with finite width and log-precision: continuous CoT, where reasoning takes the form of vectors rather than tokens, and a hybrid architecture in which transformer layers sit atop a recurrent (linear RNN) layer. In all three cases, we find that CoT can efficiently simulate any Word RAM algorithm with only a poly-logarithmic overhead in $n$. This overhead reduces to log-square when the Word RAM has a ``flat'' instruction set, and only logarithmic for multiplication-free flat instructions – in stark contrast to known CoT simulations of Turing machines, which require quadratic overhead over Word RAM.

10.
arXiv (CS.LG) 2026-06-19

Tracking Representation Dynamics in Large Language Models with Persistent Homology

arXiv:2606.19542v1 Announce Type: new Abstract: Large language models are commonly aligned through supervised fine-tuning, yet little is known about how their internal representations evolve during this process. We study alignment dynamics using persistent homology by tracking the topology of activation spaces throughout fine-tuning. Across four transformer language models ranging from 1B to 7B parameters and three alignment objectives corresponding to helpful, harmless, and mixed training data, we find that the majority of topological reorganization occurs during the earliest stages of training. A dense checkpoint analysis reveals a transient peak in topological activity followed by rapid stabilization. We further show that different alignment objectives induce distinguishable topological trajectories, while instruction-tuned and pretrained models exhibit qualitatively different patterns of evolution. Our results suggest that persistent homology provides a complementary perspective on alignment, revealing representation-level changes that are not apparent from behavioral metrics alone.

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

Online Distributional Prediction via Latent Cluster Geometry Under Drift and Corruption

arXiv:2606.18778v1 Announce Type: new Abstract: Online learning in non-stationary streams is often formulated as tracking a point estimate, but many applications require predicting the full data-generating distribution. We study online distributional prediction under drift and adversarial corruption. Our approach represents each candidate law through a latent cluster geometry: a variable-size configuration of centers that organizes probability mass and induces a predictive distribution. A Gibbs quasi-posterior over these configurations yields an online predictor by posterior averaging, and the resulting variable-dimensional posterior can be sampled with reversible-jump MCMC. The method therefore avoids specifying a parametric streaming law while retaining a structured latent space for uncertainty, regularization, and comparison. We evaluate performance by cumulative Wasserstein-1 regret against the time-varying true law. The analysis separates two effects: corruption perturbs the loss-based posterior update, whereas drift makes long-horizon posterior memory stale. We address the latter with a restarted variant that temporally localizes the same quasi-Bayesian update. The resulting high-probability bounds decompose into a PAC-Bayesian complexity term, a corruption-sensitive posterior perturbation term, and a dynamic optimal-transport term driven by \(A_T^{\mathrm{OT}}=\sum_{t=2}^T W_2^2(p_{t-1}^*,p_t^*)\). Under bounded support, stable latent geometry, predictive-map regularity, oracle realizability, localized restart windows, sublinear transport action, and sublinear corruption budget, the restarted predictor achieves sublinear cumulative Wasserstein regret. These guarantees require no parametric model for the stream, drift mechanism, or corruption process.

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

LLM Judges Have Dark Current: A Psychometric Datasheet for LLM-as-a-Judge Evaluation

LLM-as-a-judge systems are now routinely used for open-ended model evaluation, where human preference annotation is costly, slow, and difficult to reproduce. Yet these judges are often reported as scalar accuracy, win-rate, or agreement devices. We argue that a judge should instead be reported as a measurement instrument. We introduce a Judge Datasheet protocol that measures dark current under true-vacuum inputs, stable cross-sensitivity to same-quality surface variation, positional false preference, target sensitivity on a controlled quality ladder, and the criterion or operating point induced by tie instructions. The direction-stability decomposition reveals that apparent Delta0 preference can be stable surface response or disguised position bias. In a three-judge open-weight case study, Llama-3.1-8B shows high dark current and presentation-conflicted Delta0 behavior, Qwen2.5-14B is vacuum-clean and target-sensitive but mixes stable and positional over-discrimination, and Qwen2.5-32B is vacuum-clean with low stable cross-sensitivity and low positional false preference. A strict tie criterion eliminates Qwen32B Delta0 false preference but absorbs marginal Delta1 target signals into ties while preserving Delta5 sensitivity. The results show that prompting moves the criterion, not the resolution. We do not claim that the downstream mechanism hypothesis that motivated this work is confirmed; the contribution is a metrological protocol for measuring the measuring device before downstream claims are made.

13.
arXiv (CS.CL) 2026-06-24

Neuro-Symbolic Drive: Rule-Grounded Faithful Reasoning for Driving VLAs

Driving VLA models incorporating Chain-of-Thought (CoT) reasoning are attractive because they leverage pretrained VLM representations and expose intermediate decisions in natural language, yet current rationales often lack the step-by-step decision semantics needed to keep the rationale causally connected to the planned motion. We introduce Neuro-Symbolic Drive, a neuro-symbolic driving framework that supervises a driving VLA with rule-grounded reasoning traces extracted directly from classical rule-based planners. Our key observation is that rule-based planners are symbolic AI systems that already function as executable reasoning engines: they reason about active safety constraints, search over candidate maneuvers, and select a final trajectory. We instrument these planners in simulation to capture both the executed trajectory and the internal decision trace at each rule-evaluation step. Each trace is serialized into structured rule-grounded reasoning and paired with the trajectory to fine-tune Qwen3.5-4B as a driving VLA. Because these traces are derived directly from the planner states that determine the action, they ensure reasoning is structurally coupled to motion generation by construction, rather than by post-hoc alignment. On our simulator-generated benchmark, detailed rule-grounded reasoning reduces ADE@3s from 0.47 to 0.26 and miss rate from 8.30% to 6.40% under three-camera perception, and from 0.54 to 0.26 and 10.13% to 5.99% under eight-camera perception. Neuro-Symbolic Drive thus converts neuro-symbolic planning logic into structured supervision. Code base: https://github.com/XiangboGaoBarry/Neural-Symbolic-Drive.

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

UniDDT: Unifying Multimodal Understanding and Generation with Decoupled Diffusion Transformer

Unified Multimodal Models (UMMs) have emerged as a critical direction for general-purpose multimodal intelligence, integrating understanding and generation into a single framework. However, existing UMMs face prominent challenges: (1) the inherent learning conflicts between visual understanding and generation tasks, leading to suboptimal modeling in both tasks; (2) different understanding and generation visual spaces impeding scalability; (3) over-reliance on task-specific data that neglects the duality of text-image understanding and generation. To address these challenges, we propose UniDDT, which leverages a Noisy ViT encoder along with an LLM to unify semantic encoding for visual generation and understanding tasks, while employing a separate diffusion decoder to decouple diffusion decoding from text decoding. With this Noisy ViT encoder, UniDDT is able to leverage the latent space as a unified visual representation, enabling seamless compatibility between understanding and generation tasks. Thus, the scalability within the generation tasks and the semantic expressiveness within understanding tasks can be balanced. Also, we construct dual data structures from the same image-text pairs, fostering interdependence between the generation and understanding data to exploit their inherent duality. Extensive experiments demonstrate that UniDDT achieves effective unification of multimodal understanding and generation with enhanced semantic consistency and scalability. For visual generation tasks, our UniDDT achieves 0.87 GenEval score and 86.9 DPG overall score. For multimodal understanding tasks, our UniDDT achieves 1699.5 score on MME benchmark and 76.5 overall score on SEEDbench.

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

Physics-conforming Latent Twins

arXiv:2606.15053v1 Announce Type: new Abstract: Surrogate models are central to scientific machine learning, where they enable fast prediction, simulation, inference, and control for complex physical systems. For time-dependent problems, however, accurate interpolation of training trajectories is not sufficient: reliable surrogates should also respect the conservation laws, invariants, admissibility conditions, and dissipative structures that give those trajectories physical meaning. We introduce Physics-conforming Latent Twins, a framework for learning latent surrogate solution operators whose dynamics satisfy selected physical principles by design. The method builds on the Latent Twin formulation by jointly learning an encoder, a decoder, and a latent flow map between arbitrary time-indexed states, while constraining the latent dynamics to preserve or dissipate prescribed structural quantities. We develop a constraint-transfer viewpoint that connects physical structure in the original state space with compatible constraints in latent space, and prove structure-preservation bounds showing how latent enforcement improves control of physical defects after decoding. We also derive algebraic conditions for latent flow maps that preserve linear and quadratic invariants or enforce dissipative inequalities. Numerical experiments on representative ODE and PDE benchmarks demonstrate improved constraint satisfaction, structural fidelity, and qualitative long-time behavior while maintaining accurate surrogate prediction.

16.
arXiv (quant-ph) 2026-06-25

Neural network decoder confidence as a learned proxy for the logical gap

arXiv:2606.08758v2 Announce Type: replace Abstract: To utilize quantum error-correcting codes, a decoder must infer the logical sector from the measured syndrome. Beyond producing a hard logical decision, some decoders provide soft information that estimates the reliability of that decision. For minimum-weight perfect matching (MWPM), a common confidence measure is the complementary, or logical, gap. Here we test whether the logit of a graph neural network (GNN) decoder can act as a learned proxy for the logical gap. Using a pretrained GNN for the rotated surface code under uniform circuit-level noise [Physical Review Research, 7(2):023181, 2025], we compare its soft output with the MWPM complementary gap on the same sampled syndromes. We find that post-selection based on the GNN logit yields a lower logical error rate than one based on the MWPM gap. Shot-by-shot, the signed GNN confidence distribution resembles the signed MWPM gap at low and intermediate values, but assigns higher confidence to many correctly decoded shots. While both scores approximate the posterior log-likelihood ratio, the GNN confidence magnitude is closer to its ideal value. These results show that a neural-network decoder trained only on syndromes and logical labels learns both gap-like discrimination and a quantitative confidence scale, enabling confidence-based post-selection when MWPM gap estimates are unavailable, costly, or poorly matched to the noise model.

17.
arXiv (quant-ph) 2026-06-25

How to improve the accuracy of semiclassical and quasiclassical dynamics with and without generalized quantum master equations

arXiv:2603.04563v2 Announce Type: replace-cross Abstract: Semi- and quasi-classical (SC) theories can handle arbitrary interatomic interactions and are thus well-suited to predict quantum dynamics in condensed phases that encode energy and charge transport, spectroscopic responses, and chemical reactivity. However, SC theories can be computationally expensive and inaccurate. When combined with generalized quantum master equations (GQMEs), the resulting SC-GQMEs have been observed to enhance the efficiency and accuracy of SC dynamics. Yet, while the mechanism responsible for improved efficiency is clear, the underlying improved accuracy remains elusive. What is worse, SC-GQMEs can yield unphysical dynamics in challenging parameter regimes – a shortcoming that might be avoided if the mechanism of accuracy improvement were understood. Here, we uncover this mechanism. We leverage short-time analyses to prove that exact, "left-handed" time-derivatives delay the onset of SC inaccuracy, and show that their numerical integration yields dynamics with improved accuracy, even without the GQME. We find, however, that these derivatives are a double-edged sword: while offering greater short-time accuracy, they become unphysical in challenging parameter regimes. Because short-lived memory kernels can leverage short-time accuracy while circumventing long-time instability, we develop a protocol to unambiguously determine the memory kernel cutoff, even in challenging regimes where previous treatments had failed. Our insights into accuracy improvement and kernel cutoff protocol can be expected to apply to complex systems that go beyond simple models.

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

Plug-and-Play image restoration with Stochastic deNOising REgularization

Plug-and-Play (PnP) algorithms are a class of iterative algorithms that address image inverse problems by combining a physical model and a deep neural network for regularization. Even if they produce impressive image restoration results, these algorithms rely on a non-standard use of a denoiser on images that are less and less noisy along the iterations, which contrasts with recent algorithms based on Diffusion Models (DM), where the denoiser is applied only on re-noised images. We propose a new PnP framework, called Stochastic deNOising REgularization (SNORE), which applies the denoiser only on images with noise of the adequate level. It is based on an explicit stochastic regularization, which leads to a stochastic gradient descent algorithm to solve ill-posed inverse problems. A convergence analysis of this algorithm and its annealing extension is provided. Experimentally, we prove that SNORE is competitive with respect to state-of-the-art methods on deblurring and inpainting tasks, both quantitatively and qualitatively.

19.
bioRxiv (Bioinfo) 2026-06-20

Evaluation of Trypanosoma brucei Phosphofructokinase Allosteric Inhibition: An In-Silico Study

Human African trypanosomiasis, caused by a protozoan parasite Trypanosoma brucei, is a neglected tropical disease for which well-tolerated, conveniently administered, and highly efficacious medicines are still missing. Previously, T. brucei Phosphofructokinase was targeted by small-molecule inhibitor development efforts. This approach has shown promise both in vitro and in vivo. In this study, we have used these wet-lab results, evaluated the compounds already characterised by Molecular Dynamics simulations, found relationships between in silico and wet-lab data and used these observations to evaluate compounds that we selected through several different approaches of virtual screens. We observed that inhibitor-ATP interactions are highly predictive of the inhibitory activity. Several compounds selected through virtual screens have outperformed previously characterised compounds.

20.
arXiv (math.PR) 2026-06-12

Temporal Conductance and Bounds on the Voter Model for Dynamic Networks

arXiv:2606.13374v1 Announce Type: cross Abstract: The voter model is a classical stochastic process that models how opinions might spread through a network: at each step, every node lazily adopts the opinion of a random neighbour; eventually all nodes share the same opinion (consensus). Stronger connectivity should yield faster consensus. Berenbrink, Giakkoupis, Kermarrec, and Mallmann-Trenn (ICALP 2016) make this precise via the network's conductance: if the network has $m$ edges, minimum degree $d_{\min}$, and conductance at least $\phi$, then the voter model reaches consensus in expected $O(m/(d_{\min}\phi))$ steps. Their results extend to dynamic networks with fixed vertex degrees by considering the network's conductance at each time step. We introduce temporal conductance $\Phi$, a more general connectivity measure for dynamic networks. Unlike static conductance, which collapses to $0$ whenever some snapshot is disconnected, $\Phi$ captures connectivity through edges that appear at different times. We generalise the results of Berenbrink et al. from static conductance to temporal conductance, showing that the expected consensus time of the standard voter model is at most $O(m/(d_{\min}\Phi))$. Moreover, we prove that this bound is tight up to constant factors. We expect temporal conductance to be a useful primitive for analysing other dynamics on temporal networks, and potentially time-inhomogeneous Markov chains more generally.

21.
PLOS Computational Biology 2026-06-09

Evolution of phenocopying in a dynamical model of developmental trajectories

by Yuuki Matsushita, Archishman Raju Developmental trajectories are known to be canalized, or robust to both environmental and genetic perturbations. However, even when these trajectories are decanalized by an environmental perturbation outside the range of conditions to which they are robust, they often produce phenotypes similar to known mutants, called phenocopies. This correspondence between the effects of environmental and genetic perturbations has received little theoretical attention. Here, we study an abstract regulatory model that is evolved to follow a specific trajectory. We then study the effects of small and large perturbations to the trajectory, both by changing parameters and by perturbing the state at specific times. We find that the phenomenon of phenocopying emerges in evolved trajectories and is not present in a null model of randomly sampled trajectories. Our results suggest that, in this class of dynamic models, evolution can allow high-dimensional phenotypic landscapes to simultaneously exhibit robustness and phenocopying.

22.
arXiv (quant-ph) 2026-06-16

The Distribution Postulate in Algorithmic Bohmian Mechanics

arXiv:2606.16165v1 Announce Type: new Abstract: In order to make the right empirical predictions Bohmian mechanics requires a special statistical boundary condition – the distribution postulate – but it is unclear how best to understand this condition. We show how one might use the theory of algorithmic randomness to formulate the distribution postulate as an objective constraining law. The framework requires us to say something about admissible quantum-mechanical states and measurements. In return, algorithmic Bohmian mechanics (aBM) guarantees the standard Born statistics for a collection of canonical quantum experiments in the limit, not just with high probability. The algorithmic distribution postulate provides a sharp typicality condition, clarifies the status of quantum probabilities in the deterministic theory, and provides a concrete example of how notions provided by the theory of algorithmic randomness can aid in specifying the content of a physical law.

23.
arXiv (CS.CV) 2026-06-18

DART: A design-aware microfluidic chip paradigm for real-time live-cell image analysis

High-throughput microfluidic live-cell imaging generates rich single-cell data. Yet semi-automated procedures for locating regions of interest (RoIs), each containing one cell population, and removing surrounding microfluidic structures from recorded images, scale with the number of RoIs. This prevents real-time image analysis and delays time-to-insight by hours to days. We introduce the Design-Aware and Real-Time capable (DART) paradigm for microfluidic cultivation chips, which aligns the CAD blueprint with the physical chip and thereby enables throughput-independent localization of all RoIs and fully automated image processing across diverse RoI geometries and chip layouts. DART establishes this alignment through embedded fiducial markers and deep-learning-based marker detection. We validate DART using the Swiss Army Knife chip, which combines eight structurally distinct RoI designs across 1164 RoI locations. DART localizes all RoIs in five minutes, removes microfluidic structures from raw microscopy images in 40 ms, and performs fully automated image analysis, including cell segmentation, in under 1.1 s per image. Together, these capabilities establish DART as an end-to-end hardware-software paradigm with real-time-capable analysis that paves the way toward closed-loop and outcome-driven smart microscopy.

24.
arXiv (CS.AI) 2026-06-19

eCNNTO: A Highly Generalizable ConvNet for Accelerating Topology Optimization

arXiv:2606.19921v1 Announce Type: new Abstract: This work proposes an element-based Convolutional Neural Network (CNN) to accelerate density-based Topology Optimization (TO), termed eCNNTO. TO generally undergoes a large number of iterations, where finite element analysis is performed in every iteration, leading to the efficiency bottleneck especially when dense meshes are used to achieve high-resolution designs. To address this limitation, eCNNTO is proposed to build upon Kallioras et al. (2020), where a Deep Belief Network (DBN) was trained for every element to predict its near-optimal density from its early history, thereby skipping the great majority of iterations and significantly accelerating the TO procedure. However, the method lacks spatial correlations among neighboring elements and may lead to disconnected features in the final structure. The proposed method employs CNN with residual connections to address this issue. On top of it, a novel training strategy is introduced to further enhance the optimization efficiency, where the training dataset consists of the final stage density histories rather than early ones. This change can also help reduce the required training data size. eCNNTO requires only a small dataset to train and yet it can be generalized to problems with largely different boundary conditions, loading cases, design domain geometries, mesh resolutions, as well as non-design domains. In the end, the generalization capabilities and efficiency of eCNNTO are demonstrated through a variety of examples in two and three dimensions, achieving up to 90% and 97% reduction of iterations, respectively.

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

Bergson: An Open Source Library for Data Attribution

arXiv:2606.11660v1 Announce Type: new Abstract: Data attribution is a promising field in interpretability that aims to explain model behavior through the influence of its training data, with applications including debugging undesirable model behavior and training dataset curation. However, significant engineering effort is required to perform it at scale, and many cutting edge techniques lack open-source tooling and support. Bergson is an open source library that aims to enable faster progress in the field by providing a host of techniques that scale to very large language models and pre-training datasets. The library natively supports on-disk gradient stores and multi-node distributed training, and provides quality of life tools for researchers. Finally, we introduce the first open-source implementations of three leading data attribution methods: MAGIC, SOURCE, and TrackStar. The library is available at https://github.com/EleutherAI/bergson .