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01.
Nature Medicine 2026-06-15

Plasma proteomic signatures of cellular aging predict human disease

Aging is asynchronous across cells and organs. Here we tested whether plasma proteomics can be used to analyze cell type-specific aging. From analyses of over 7,000 plasma proteins measured in 60,542 individuals, we developed machine learning models to estimate the biological age of over 40 cell types spanning neuronal, immune, glial, endocrine, epithelial and musculoskeletal origins. We observed that 20–25% of individuals exhibited accelerated aging in a single cell type and 1–3% in 10 or more cell types. Cellular aging signatures were associated with disease status and predicted incident disease and mortality over 15 years of follow-up. Individuals with the APOE4 genotype showed older astrocytes but younger macrophages compared to APOE3 carriers, whereas the APOE2 genotype had inverse associations. Moreover, extreme astrocyte aging tripled the risk of incident Alzheimer’s Disease in individuals with two APOE4 alleles, while youthful astrocytes reduced risk. Individuals with extremely aged compared to youthful skeletal myocytes exhibited a 12.7-fold higher risk of developing amyotrophic lateral sclerosis. In individuals who smoked, extreme respiratory epithelial cell aging was associated with a 58% higher lung cancer risk compared to smoking alone. Specific cellular vulnerabilities and cumulative cellular aging burden influenced survival, with youthful immune and neuronal cell types conferring protective effects. Finally, we developed a polycellular aging risk score that stratified mortality risk across cohorts and proteomics platforms. These findings establish a framework for quantifying human physiology at cellular resolution, revealing heterogeneous aging trajectories and their impact on disease susceptibility and resilience. The biological age of individual cell types can be evaluated using plasma proteomics, revealing diverse aging profiles across more than 40 cell types and links between the accelerated aging of specific cell types and disease.

02.
arXiv (CS.LG) 2026-06-17

Learning and Generating Mixed States Prepared by Shallow Channel Circuits

arXiv:2604.01197v4 Announce Type: replace-cross Abstract: Learning quantum states from measurement data is a central problem in quantum information and computational complexity. In this work, we study the problem of learning to generate mixed states on a finite-dimensional lattice. Motivated by recent developments in mixed state phases of matter, we focus on arbitrary states in the trivial phase. A state belongs to the trivial phase if there exists a shallow preparation channel circuit under which local reversibility is preserved throughout the preparation. We prove that any mixed state in this class can be efficiently learned from measurement access alone. Specifically, given copies of an unknown trivial phase mixed state, our algorithm outputs a shallow local channel circuit that approximately generates this state in trace distance. The sample complexity and runtime are polynomial (or quasi-polynomial) in the number of qubits, assuming constant (or polylogarithmic) circuit depth and gate locality. Importantly, the learner is not given the original preparation circuit and relies only on its existence. Our results provide a structural foundation for quantum generative models based on shallow channel circuits. In the classical limit, our framework also inspires an efficient algorithm for classical diffusion models using only a polynomial overhead of training and generation.

03.
Nature (Science) 2026-06-17

A distant brown dwarf coplanar to a warm Jupiter and a hot super-Earth

In transiting planetary systems, in which planetary sizes are accurately determined from transit observations, the presence of transit-timing variations1 (TTVs), especially when combined with radial velocity (RV) data, provides powerful constraints on masses and orbital eccentricities. Together, these measurements offer crucial insights into system architecture, formation mechanisms and dynamical evolution. We present long-term RV and transit/TTV monitoring of the relatively young star (age approximately 1 Gyr) TOI-201, revealing an exceptional multi-planet system composed of a hot super-Earth (SE) size planet transiting every 5.8 days, a warm Jupiter (WJ) on a 53-day orbit and an eccentric (e = 0.62) low-mass brown dwarf (BD) on an approximately 8-year orbit, with an estimated mass MBD of about 16 Jupiter masses. The BD is the longest-period transiting substellar object ever characterized by means of RVs and the only one known to be coplanar with inner planets. The architecture of this system suggests that the SE was formed isolated and in the innermost region of the gaseous disk. On the other hand, the orbital configuration of the outer companions suggests a nearly in situ formation of both objects, with the WJ forming in a dense inner disk. Alternatively, the BD might have formed farther out and migrated inward, while increasing its eccentricity owing to interactions with the disk. Analysis of long-term radial velocity data and transit time variations, induced by a super-Earth, a warm Jupiter and a brown dwarf in a coplanar orbit around the relatively young star TOI201.

04.
arXiv (math.PR) 2026-06-11

The Geometry of Admissible Short Selling in Discrete-Time Stochastic Portfolio Theory

arXiv:2606.11191v1 Announce Type: cross Abstract: While discrete-time Stochastic Portfolio Theory (SPT) provides a robust framework for market analysis, existing work on functional generation has predominantly focused on long-only portfolios defined on the entire unit simplex. This paper extends the geometric framework of functional generation to the broader class of bankruptcy-proof long-short portfolios defined on local market state spaces. We establish that, within this admissible setting, pseudo-arbitrage is fully characterized by the concavity of the generating function on the market state space, thereby relaxing the usual global domain requirement. A central contribution of this work is a geometric characterization of the short-selling mechanism. We prove that the presence of short selling is equivalent to the negativity of the maximal concave extension of the generating potential. This phenomenon is linked to the steepness of the logarithmic gradient as the market approaches a zero boundary nested inside the simplex. To systematically exploit this mechanism, we introduce the barycentric scaling transformation, a constructive methodology that maps classical long-only generating functions onto restricted domains to engineer admissible strategies with controlled short-selling exposure. Finally, through the analysis of specific shrunken portfolios, we identify a geometric phase transition: under suitable boundary conditions, admissible strategies exhibit a long-only core and a short-selling region in a qualitative sense (without asserting an exact partition of the state space). This provides a unified geometric perspective on relative arbitrage beyond the long-only constraint.

05.
arXiv (CS.AI) 2026-06-24

MultiMem: Measuring and Mitigating Memorization in Multi-Modal Contrastive Learning

arXiv:2606.22220v2 Announce Type: replace-cross Abstract: Memorization in machine learning models enables high performance on rare in-distribution samples by capturing their atypical patterns. However, it also causes harmful retention of noise and outliers, degrading generalization. While memorization has been extensively studied in both supervised and self-supervised learning in the vision domain, it remains unexplored in multi-modal contrastive learning. We address this gap by introducing MultiMem, the first metric designed to quantify memorization in multi-modal contrastive learning. Through our systematic analysis, we demonstrate that cross-modal semantic misalignment has the strongest influence on memorization, with text being the dominant modality driving memorization, followed by video, image, and audio. We show that targeted augmentations applied across all modalities effectively reduce memorization as measured by our MultiMem metric and improve model performance. Overall, this work establishes the first framework for measuring and mitigating memorization in multi-modal contrastive learning, preventing harmful data retention and contributing to higher-performing models.

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

UNIEGO: Proxies as Mediators for Unified Egocentric Video Representation Learning

arXiv:2606.20559v1 Announce Type: cross Abstract: Egocentric video understanding is inherently limited by the narrow perspective of wearable cameras: a single viewpoint, a single modality, a single model cannot capture the full richness of human action. We argue that a truly expressive egocentric representation must subsume complementary knowledge across viewpoints, modalities, and foundation model representations, yet remain deployable from egocentric video alone. To this end, we introduce a hierarchical multi-teacher distillation framework that produces UNIEGO, a unified egocentric encoder trained with nine teachers spanning ego-exo viewpoints, RGB, depth, and skeleton modalities, and four foundation models. Rather than distilling directly from heterogeneous teachers whose incompatible architectures and feature geometries induce conflicting gradients, our framework interposes a layer of representation-specific Proxy models that translate diverse teacher knowledge into a homogeneous egocentric space. A second distillation stage, Selective Proxy Distillation (SPD), then adaptively selects, for each training sample, the subset of proxies that are both correct and confident, distilling exclusively from reliable supervision and suppressing erroneous signals. SPD is further stabilized by initializing UNIEGO as a learned convex combination of proxy parameters, placing the unified model in a well-conditioned region of the loss landscape before distillation begins. UNIEGO achieves state-of-the-art performance across three egocentric video understanding tasks - action recognition, video retrieval, and action segmentation on three challenging ego-exo benchmarks, outperforming naive multi-teacher distillation baselines and demonstrating that structured, proxy-mediated knowledge transfer yields richer and more discriminative egocentric representations.

07.
arXiv (math.PR) 2026-06-16

Purely unrectifiable sets, fractal percolation and graphs of functions

arXiv:2606.15745v1 Announce Type: cross Abstract: This paper contains a survey of some of the results of the author related to unrectifiablity and is an extended version of the author's talk given at the Second Winter School Geometric Measure Theory Rectifiability vs. Pure Unrectifiability in Hanghzou, China. These results include irregular/purely unrectifiable $1$-sets on the graphs of continuous functions like the Takagi, the Weierstrass-Cellerier and the typical (in the sense of Baire) continuous function. It is also discussed that there exists $ {\alpha}_{0}\alpha_0$. The background of the $1$-unrectifiability is discussed in more detail.

08.
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.

09.
arXiv (CS.AI) 2026-06-17

PreAct: Computer-Using Agents that Get Faster on Repeated Tasks

作者:

arXiv:2606.17929v1 Announce Type: new Abstract: Computer-using agents drive real software through the screen – clicking and typing – but they solve every task from scratch: asked to repeat a task, an agent re-reads the screen, re-reasons every tap, and pays the full cost again. We present PreAct, which lets such an agent get faster on tasks it has done before. The first time it succeeds, PreAct compiles the run into a small state-machine program-states that check the screen, transitions that act-and on later runs replays it directly instead of invoking the agent 8.5-13x faster, with no per-step language-model calls. Replay is not blind: at each step PreAct checks that the screen matches what the program expects before acting, and hands control back to the agent the moment something is off. PreAct applies the same discipline when deciding what to keep: a freshly compiled program enters the store only if, re-run from a clean state, an independent evaluator confirms it solved the task-catching programs that replay to their last step yet leave the task undone. Across a mobile, a desktop, and a web benchmark, this store-time check separates repeated runs that improve from ones that degrade as faulty programs accumulate, worth 1.75-2.6 tasks per benchmark, the same direction on all three; a fallback that explores afresh when no program fits brings PreAct level with a strong record-and-replay baseline. We also report what did not matter: prompt wording, runtime guardrails, and whether a language model or a plain embedding retriever selects which program to reuse.

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

Why Tree-Style Branching Matters for Thought Advantage Estimation in GRPO

Group Relative Policy Optimization (GRPO) trains Chain-of-Thought reasoning with verifiable rewards, but estimating thought-level advantages without value functions often suffers from high variance. Although tree-style branching is used in practice to reduce variance, it lacks a theoretical explanation of why it works and whether it is important or potentially necessary. We study thought-level advantage estimation in GRPO from a variance perspective under a minimal tree-style setting where multiple continuations are sampled for each thought. Using the multivariate delta method, we reveal a sampling-dimension asymmetry. Increasing sampled thoughts ($K$) leaves a strictly positive estimation-variance floor, whereas increasing continuations per thought ($M$) drives the leading-order estimation variance to zero at rate $1/M$. This implies that, within the fixed-temperature GRPO-style estimator without value models studied here, accurate thought-level advantage estimation cannot be achieved by scaling thought sampling alone, making continuation-level branching a principled and potentially necessary mechanism rather than a heuristic. Experiments further provide empirical evidence for its effectiveness and potential necessity, demonstrating improved optimization stability, training efficiency, and final performance not only in math but also across vision domains and under different model architectures and sizes.

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

Efficient Analytic Uncertainty Quantification for Multi-Modal Regression

arXiv:2606.25188v1 Announce Type: new Abstract: Efficient uncertainty quantification (UQ) is essential for trustworthy large-scale learning. Existing UQ methods for regression tasks mainly operate under the assumption that the conditional label marginal satisfies single-peak parametric models, e.g., Gaussians, where the negative log-likelihood function simplifies to the mean square error. However, such single-peak assumptions fail in regression tasks featuring multi-modal distributions. On the other hand, semi-parametric methods which achieve strong regression performance for multi-modal distributions often lack efficient quantification on their prediction variances. In this work, we extend UQ techniques based on Variational Bayesian Inference (VBI) to two widely used semi-parametric regression models that yield histogram-like reconstructions of the conditional label densities: Quantile Regression (QR) and Classification Restoration (CR). Our approach introduces a unified, distribution-agnostic framework that simultaneously achieves accurate estimation of complex conditional distributions and highly efficient UQ. Theoretically, our method is grounded in novel formulations of QR and CR within the VBI framework, yielding analytic Evidence Lower Bounds (ELBO) to streamline training and a closed-form or analytically approximated predictive density for efficient inference. Empirically, we evaluate our methods on three large-scale regression benchmarks with multi-modal label distributions. Our framework outperforms state-of-the-art multi-modal regression baselines, and even matches predictive performance of computationally expensive ensemble models. Furthermore, by leveraging epistemic uncertainty estimation, our approach enables highly data-efficient active learning strategies.

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

History of the Muddy Children Puzzle

arXiv:2606.13703v1 Announce Type: new Abstract: The Muddy Children Puzzle is a puzzle about knowledge and ignorance that has been inspiring for the development of epistemic logic. Who came up with it first? This is unclear. We trace the origin of the Muddy Children Puzzle through logical and literary publications over the past two centuries. The puzzle inspired a numerous variations such as involving numbers or coloured hats. We also present a novel hats puzzle involving self-reference.

13.
arXiv (CS.CV) 2026-06-18

Vines-DB: An RGB image dataset for multi-species ornamental vine segmentation

The Vines-DB dataset contains 1,218 original high-resolution RGB images of seven ornamental vine species collected under field conditions at the Utah Agricultural Experiment Station's Greenville Research Farm in Logan, Utah, USA. The dataset was generated from 168 individual vine plants that were transplanted in 2022 and photographed repeatedly across multiple months during the 2023 and 2024 growing seasons (July-October). Images were captured with an iPhone 16 Pro equipped with a 48 MP camera between 10:00 AM and 12:00 PM under daylight. Vines were grown on 1.2m x 2.4m trellises and photographed from a distance of 1m against black or white Styrofoam backdrops to improve contrast and reduce background noise. The dataset includes Akebia quinata, Campsis radicans, Hydrangea anomala petiolaris, Lonicera x heckrottii, Campsis x tagliabuana 'Madame Galen', Parthenocissus quinquefolia, and Wisteria floribunda. All original images were manually annotated in Roboflow by trained annotators to produce polygon-based instance segmentation masks for eight classes, including seven species and background. After preprocessing and data augmentation, the working dataset was expanded to 2,307 images for model development and evaluation. The augmented dataset was divided into 2,019 training images, 192 validation images, and 96 test images using stratified sampling to maintain balanced representation. Vines-DB supports the development and evaluation of deep learning models for multi-class instance segmentation in precision horticulture and urban ecology. The dataset enables applications such as automated canopy cover estimation, species identification, and scalable field phenotyping. In addition, repeated monthly imaging of the plants captures temporal variation in canopy development and plant appearance, increasing the dataset's utility for segmentation benchmarking under realistic field conditions.

14.
arXiv (CS.LG) 2026-06-11

A Data-Centric Framework for Detecting and Correcting Corrupted Labels

arXiv:2606.11699v1 Announce Type: new Abstract: The performance of machine learning and deep learning models largely depends on the quality of the training data. However, the quality of the real-world datasets is often compromised by noisy labels, which can substantially degrade model accuracy and reliability. To address this challenge, we propose Relabeler, an end-to-end data-centric framework for detecting and correcting corrupted labels. For corrupted label detection, Relabeler jointly leverages both local and global relationships among data instances to identify potentially noisy samples. After detecting suspicious instances, Relabeler further performs label correction by estimating the most probable clean label for each instance based on both its input features and observed noisy label. Extensive experiments across multiple datasets, noise types, and noise rates demonstrate that Relabeler consistently outperforms state-of-the-art baselines, achieving up to 58% improvement in label correction precision and 6% improvement in downstream task performance.

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

Efficient Stochastic Optimisation via Sequential Monte Carlo

arXiv:2601.22003v2 Announce Type: replace-cross Abstract: The problem of optimising functions with intractable gradients frequently arises in machine learning and statistics, ranging from maximum marginal likelihood estimation procedures to fine-tuning of generative models. Stochastic approximation methods for this class of problems typically require inner sampling loops to obtain (biased) stochastic gradient estimates, which rapidly becomes computationally expensive. In this work, we develop sequential Monte Carlo (SMC) samplers for optimisation of functions with intractable gradients. Our approach replaces expensive inner sampling methods with efficient SMC approximations, which can result in significant computational gains. We establish convergence results for the basic recursions defined by our methodology which SMC samplers approximate. We demonstrate the effectiveness of our approach on the reward-tuning of energy-based models within various settings.

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

Evaluating and Combating the Impact of Concept Drift on the Performance of Machine Learning-Based Phishing Detection Systems

arXiv:2606.11471v1 Announce Type: cross Abstract: The expansion of the digital domain has resulted in a substantial increase in digital communication, with email emerging as one of the most prominent channels. The proliferation of email communication is apparent in both professional and personal contexts, thereby creating numerous vulnerabilities for malicious actors to exploit. Spam emails, a form of unsolicited correspondence often bearing malicious intent towards recipients, have been an ongoing challenge for email users since the inception of email technology, and this problem has been exacerbated by the growth of the digital landscape. Email spam filters are integral components of email clients, engineered to identify potentially harmful messages and alert users to their malicious content. Phishing, frequently the initial phase of malware-based attacks, is evolving rapidly, with malware becoming increasingly sophisticated over time. A widely adopted approach for detecting malicious activity within malware and spam domains is the application of machine learning. Our aim is to assess the impact of the evolution within the spam email domain on these machine learning-based detection systems and to explore strategies for mitigating associated performance degradation.

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

On the entanglement induced by the deformation of phase-space

arXiv:2606.17587v1 Announce Type: new Abstract: Most quantum gravity theories propose that the fundamental concept of space-time is mostly compatible with quantum theory in noncommutative (NC) space. In the present paper, we revisit the notion of entanglement induced by NC deformations of phase space. The positive partial transpose (PPT) criterion for separability of bipartite Gaussian states is extended to a general class of Bopp's shift. In particular, we have considered both the position-position and momentum-momentum noncommutativity, with deformation parameters $\theta$ and $\eta$, respectively. It turns out that $\theta$ and $\eta$ induce the entanglement. We have directly applied the formalism for an anisotropic two-dimensional harmonic oscillator. Peres-Horodecki separability condition leads to a constraint equation for the parameter values of the oscillator in NC space. It turns out that the bipartite Gaussian state is almost always entangled in deformed space. To implement the theoretical idea, we provide an outline for a gedankenexperiment to identify the signature of phase-space noncommutativity, i.e., quantum gravity. In particular, the gedankenexperiment is devised to test the separability of supposedly separable Gaussian states in the usual commutative space, through the covariance matrix, which is constructed via measured output photocurrents after interaction of input Gaussian states and reference states. If the experiment shows that the supposedly separable states are actually entangled, then the entanglement is created through the intermediate background noncommutative space, which is a signature of the quantum nature of gravity.

18.
arXiv (CS.LG) 2026-06-15

Deep Learning and Elicitability for McKean-Vlasov FBSDEs With Common Noise

arXiv:2512.14967v2 Announce Type: replace Abstract: We present a novel numerical method for solving McKean–Vlasov forward–backward stochastic differential equations (MV–FBSDEs) with common noise, combining Picard iterations, elicitability and deep learning. The key innovation involves elicitability to derive a pathwise loss function, enabling efficient training of neural networks to approximate both the backward process and the conditional expectations arising from common noise, without requiring computationally expensive nested Monte Carlo simulations. The mean-field interaction term is parameterized via a recurrent neural network trained to minimize an elicitable score, while the backward process is approximated through a hybrid feedforward and recurrent network representing the decoupling field. We validate the algorithm on a systemic-risk inter-bank borrowing and lending model, where analytical solutions exist, demonstrating accurate recovery of the true solution. We further extend the model to quantile-mediated interactions, showcasing the flexibility of the elicitability framework beyond conditional means or moments. Finally, we apply the method to a non-stationary Aiyagari–Bewley–Huggett economic growth model with endogenous interest rates, illustrating its applicability to complex mean-field games without closed-form solutions.

19.
arXiv (CS.AI) 2026-06-25

Holographic Memory for Zero-Shot Compositional Reasoning in Knowledge Graphs: A Mechanistic Study of Where and Why It Fails

arXiv:2606.24948v1 Announce Type: cross Abstract: Knowledge graph embedding (KGE) models predict single-hop links well but have no mechanism for zero-shot compositional queries: multi-hop questions whose relation chains never appeared during training. Holographic Reduced Representations (HRR), which bind and unbind symbols via circular convolution, are a theoretically attractive candidate, since binding is approximately invertible and associative. We test whether this promise holds. We study two holographic memory variants, real-valued HRR and phase-only Fourier HRR (FHRR), each with a modern Hopfield cleanup, on FB15k-237 over five seeds. Four findings follow. First, both are competitive single-hop retrievers (filtered MRR 0.358 +/- 0.002 for HRR, 0.350 +/- 0.021 for FHRR). Second, neither composes zero-shot: accuracy stays at chance across all cleanup temperatures. Third, the main contribution, we localise the failure mechanistically. A hop-1 probe shows the memory recovers the correct intermediate entity with high fidelity (MRR 0.896 +/- 0.002 for HRR), yet composition still fails even with a verified-correct intermediate. A second probe shows why: posing the ground-truth second-hop fact as a standalone atomic query, bypassing composition entirely, already recovers it at only 0.26 to 0.48x average atomic accuracy, uniformly across relation fan-out. The bottleneck is not the bind-unbind algebra or the cleanup; it is that facts compositional chains pass through are intrinsically harder for the superposed memory to retrieve, a capacity and interference effect present already at a single hop. Fourth, we prove (Lemma 4.1) that FHRR's softmax cleanup is not phase-equivariant, compounding the primary failure on the minority of chains where hop-1 itself errs. Fixing zero-shot composition requires improving retrieval capacity under superposition, not just redesigning the cleanup.

20.
arXiv (CS.AI) 2026-06-19

Latent Confounded Causal Discovery via Lie Bracket Geometry

arXiv:2606.19610v1 Announce Type: cross Abstract: Recent work on Kan-Do-Calculus (KDC) has established that the boundary between passive observation and active intervention in causal inference is a category-theoretic bi-adjunction, with interventions modeled by left Kan extensions and conditioning by right Kan extensions. This paper introduces two causal discovery algorithms under latent confounding, building on the information-geometric and categorical consequences of KDC. In smooth statistical settings, Radon-Nikodym derivatives between observational and interventional measures induce local causal vector fields; failures of these fields to close under Lie brackets become computable Frobenius residuals, which we interpret as witnesses of failed visible integrability and possible latent or unmodeled structure. Our first algorithm, BRIDGE (Bracket Residuals for Interventional Discovery and Geometric Estimation), combines an interventional density or Radon-Nikodym-ratio engine with a geometric screen that proposes a high-recall family of admissible arrows, identifies non-closing visible pairs as latent-obstruction candidates, and passes the reduced family to downstream score-based or differentiable discovery routines. The second algorithmic contribution, Spectral Kan-Do Flow Matching (SKFM), learns amortized intervention fields and factors latent curvature spectrally, exposing the direct Lie-space endpoint toward which BRIDGE points. A detailed set of experiments show that both algorithms are capable of discovering causal models with latent confounders while collapsing the super-exponential space of possible DAGs by many orders of magnitude. This paper introduces a new paradigm in causal discovery, where latent structure is inferred directly from the geometry of intervention-induced flows.

21.
bioRxiv (Bioinfo) 2026-06-18

Bioinf-Farma: supervised integration of epitope prediction and recombinant protein developability for automated vaccine candidate prioritization

Vaccine antigen discovery requires prioritizing protein candidates according to both immunogenic potential and recombinant expression feasibility. These properties are typically evaluated using separate computational tools, requiring researchers to integrate heterogeneous outputs through ad hoc workflows. Here, we present BIOINF-farma, a modular platform integrating epitope prediction and developability assessment for rational antigen selection within a unified environment. Candidates can be submitted as amino acid sequences or three-dimensional structures. When experimental structures are unavailable, BIOINF-farma automatically searches for models in AlphaFold DB or performs structure prediction using Boltz-2, ensuring a standardized structural representation for downstream analyses. Antigenicity is quantified by combining structure-based conformational epitope signals (MLCE/REBELOT-BEPPE) and sequence-based linear epitope propensity scores (BepiPred 3.0) into a protein-level Antigenicity Score, with a classification threshold optimized on a manually curated validation dataset. Developability is evaluated through two supervised Random Forest meta-learners that integrate three solubility predictors (DeepSoluE, SoluProt, Protein-Sol) and three thermal stability predictors (TemStaPro, ProLaTherm, BertThermo), whose outputs are combined into an Expression Efficiency Score (EES). By integrating complementary predictive signals, the meta-learning framework achieves greater accuracy and robustness than individual predictors while maintaining performance across a broad range of sequence identities. The Antigenicity Score effectively discriminates antigenic from non-antigenic proteins with a large effect size, whereas EES successfully distinguishes soluble from insoluble outcomes on an independent panel of recombinant proteins expressed in Escherichia coli. BIOINF-farma jointly assesses antigenicity and expression feasibility within a single framework. Its modular architecture facilitates the incorporation of future predictive methods, while its web-based interface makes the full pipeline accessible to users without programming expertise, supporting rapid candidate triage in vaccine research and emerging pathogen responses.

22.
arXiv (CS.LG) 2026-06-24

SEED: Semi-supervised Continual MalwarE Detection for Tackling ConcEpt Drift on a BuDget

arXiv:2605.24903v2 Announce Type: replace-cross Abstract: Machine learning based malware detectors become obsolete over time due to concept drift in benign and malware applications. Recent methods rely on fully labeled data and use hierarchical contrastive loss (HCL) with active learning to improve robustness against drift by exploiting semantic structure in malware representations. However, obtaining labeled data in the security domain is difficult. Under partially labeled settings, HCL suffers significant performance degradation in detecting unseen malware, especially on datasets such as BODMAS where strong semantic structure may not exist. In this paper, we propose SEED, a semantic-structure-agnostic method for malware detection under limited supervision. SEED combines a tailored binary cross-entropy objective with semi-supervised continual learning and active learning. For partially labeled seen tasks, unlabeled samples are projected into a representation space constructed from previously seen data using singular value decomposition, and paired with suitable labeled samples to encourage representation consistency. For unseen tasks with fully unlabeled data, uncertainty is quantified using cosine distance in representation space, and the most uncertain samples are selected for analyst labeling. We evaluate SEED on both Windows and Android malware datasets. Using only 20% labeled data on seen tasks, SEED achieves average AUT improvements of 40% on BODMAS and 14% on AndroZoo for unseen malware detection compared to HCL* (the semi-supervised adaptation of HCL), while remaining competitive on APIGraph. Finally, we introduce a delayed buffer update strategy to reduce label noise propagation during replay and improve learning stability.

23.
Nature (Science) 2026-06-23

Daily briefing: NASA to launch satellite-rescue mission

作者:

The space agency will lift the orbit of a falling satellite by around 200 kilometres. Plus, Europe’s efforts to take on the US and China as a science superpower and the narcissism of bosses who want to nix remote working. The space agency will lift the orbit of a falling satellite by around 200 kilometres. Plus, Europe’s efforts to take on the US and China as a science superpower and the narcissism of bosses who want to nix remote working.

24.
arXiv (CS.LG) 2026-06-17

On Surjectivity of Neural Networks: Can you elicit any behavior from your model?

arXiv:2508.19445v3 Announce Type: replace Abstract: Given a trained neural network, can any specified output be generated by some input? Equivalently, does the network correspond to a function that is surjective? In generative models, surjectivity implies that any output, including harmful or undesirable content, can in principle be generated by the networks, raising concerns about model safety and jailbreak vulnerabilities. In this paper, we prove that many fundamental building blocks of modern neural architectures, such as networks with pre-layer normalization and linear-attention modules, are almost always surjective. As corollaries, widely used generative frameworks, including GPT-style transformers and diffusion models with deterministic ODE solvers, admit inverse mappings for arbitrary outputs. By studying surjectivity of these modern and commonly used neural architectures, we contribute a formalism that sheds light on their unavoidable vulnerability to a broad class of adversarial attacks.

25.
arXiv (quant-ph) 2026-06-12

Kerr-induced nonreciprocal transparency and group delay in a hybrid cavity magnomechanical system

arXiv:2606.13412v1 Announce Type: new Abstract: We propose a scheme for realizing nonreciprocal transparency, Fano resonances, and slow/fast light in a hybrid cavity magnomechanical system containing two YIG spheres and a mechanical resonator. The nonreciprocal behavior originates from the magnon Kerr nonlinearity, which induces direction-dependent frequency shifts and modifies the interference pathways among cavity photons, magnons, and phonons. We show that the hybrid system supports multiple transparency windows arising from magnon- and magnomechanical-induced interference processes. The Kerr interaction strongly reshapes these transparency features, producing asymmetric Fano line shapes and enabling controllable nonreciprocal transmission. Furthermore, the associated dispersion exhibits pronounced directional asymmetry, leading to giant differences in the group delay for opposite propagation directions and allowing reversible switching between slow- and fast-light regimes. We investigate the roles of hybrid coupling strengths and dissipation channels and identify parameter regimes where the nonreciprocal response is maximized. These findings establish Kerr-engineered magnomechanical systems as promising platforms for integrated nonreciprocal microwave photonics and quantum information technologies.