julilili42/papers huggingface dataset:
The Open Aurignacian Project: 3D scanning and the digital preservation of the Italian Paleolithic record
2025-06-19

Abstract Here, we introduce an open-access database of 3D models of stone tools (n = 2,016) from four Early Upper Paleolithic sequences excavated south of the Alps and along Peninsular Italy, including Grotta della Cala, Grotta di Castelcivita, Grotta di Fumane, and Riparo Bombrini. Available through four self-standing Zenodo repositories, these models enable in-depth analysis of core reduction procedures, reduction intensity, and shape variability. Unlike other repositories, this database has been actively used to address archaeological questions, providing a comprehensive demonstration of the use of 3D models in lithic analysis. The Open Aurignacian Project utilizes various scanning devices, including the Artec Spider, Artec Micro, and micro-computed tomography, with a focus on enhancing the reproducibility and accessibility of archaeological data. This paper presents the scanning methodology, dataset organization, and technical validation of the project, while also discussing the scientific potential of these data to foster cross-continental research collaboration. Our open-sharing initiative is designed to stimulate inter-regional studies of human behavioral evolution, offering new opportunities to address questions in Paleolithic studies through the FAIR principles.
Revealing the range of equally likely estimates in the admixture model
2025-06-19

Abstract Many ancestry inference tools, including Structure and Admixture, rely on the admixture model to infer both, allele frequencies p and individual admixture proportions q for a collection of individuals relative to a set of hypothetical ancestral populations. We show that under realistic conditions the likelihood in the admixture model is typically flat in some direction around a maximum-likelihood estimate (q^,p^). In particular, the maximum-likelihood estimator is nonunique and there is a complete spectrum of possible estimates. Common inference tools typically identify only a few points within this spectrum. We provide an algorithm which computes the set of equally likely (q~,p~), when starting from (q^,p^). It is analytic for K=2 ancestral populations and numeric for K&amp;gt;2. We apply our algorithm to data from the 1000 genomes project, and show that inter-European estimators of q can come with a large set of equally likely possibilities. In general, markers with large allele frequency differences between populations in combination with individuals with concentrated admixture proportions lead to small areas with a flat likelihood. Our findings imply that care must be taken when interpreting results from STRUCTURE and ADMIXTURE if populations are not separated well enough.
Human dorsal forebrain organoids show differentiation-state-specific protein secretion
2025-06-19

The human brain microenvironment undergoes dynamic changes during development, which have been incompletely characterized in <i>in vitro</i> models including neural organoids. Here, we used liquid chromatography-mass spectrometry to investigate proteome and secretome changes in human dorsal forebrain organoids derived from three hiPSC lines at days 20, 35, and 50 of differentiation. Proteome and immunohistochemical analysis revealed reduced proliferation and increased differentiation of progenitor cells gradually over time. In contrast, secretome analysis showed distinct characteristics at each timepoint - notably, at day 35, the numbers of cell adhesion molecules, synaptic proteins, and proteases were increased. Taken together, we present a resource describing the dynamic features of a neural organoid proteome and secretome across different genetic backgrounds. We describe the unique niche composition of neural organoids during the period of neurogenesis and suggest that synaptic proteins may play a role in guiding neurogenesis.
Publisher Correction: Genomic reanalysis of a pan-European rare-disease resource yields new diagnoses
2025-06-19

Correction to: Nature Medicinehttps://doi.org/10.1038/s41591-024-03420-w, published online 17 January 2025. In the version of this article initially published, collaborators in the Solve-RD DITF-GENTURIS, Solve-RD DITF-ITHACA, Solve-RD DITF-EURO-NMD, Solve-RD DITF-RND and Solve-RD consortia were not listed correctly as authors in the metadata associated with this paper, as is now amended in the HTML and PDF versions of the article.
Some small Sylow numbers
2025-06-19

Abstract Given a prime p and a finite group G, let <m:math xmlns:m="http://www.w3.org/1998/Math/MathML"> <m:mrow> <m:msub> <m:mi>s</m:mi> <m:mi>p</m:mi> </m:msub> <m:mo>⁢</m:mo> <m:mrow> <m:mo stretchy="false">(</m:mo> <m:mi>G</m:mi> <m:mo stretchy="false">)</m:mo> </m:mrow> </m:mrow> </m:math> s_{p}(G) denote the number of Sylow p-subgroups of G. Suppose that this Sylow number is small in terms of the prime p. What can be said, then, about the structure of G, the order of a Sylow p-subgroup, or the union of the Sylow p-subgroups? In answering these questions, it is appropriate to assume that G is generated by its Sylow p-subgroups and that the intersection of the normalizers of the Sylow p-subgroups is trivial (which does not alter <m:math xmlns:m="http://www.w3.org/1998/Math/MathML"> <m:mrow> <m:msub> <m:mi>s</m:mi> <m:mi>p</m:mi> </m:msub> <m:mo>⁢</m:mo> <m:mrow> <m:mo stretchy="false">(</m:mo> <m:mi>G</m:mi> <m:mo stretchy="false">)</m:mo> </m:mrow> </m:mrow> </m:math> s_{p}(G) ). If G is such a p- reduced group, it is a transitive permutation group of degree <m:math xmlns:m="http://www.w3.org/1998/Math/MathML"> <m:mrow> <m:msub> <m:mi>s</m:mi> <m:mi>p</m:mi> </m:msub> <m:mo>⁢</m:mo> <m:mrow> <m:mo stretchy="false">(</m:mo> <m:mi>G</m:mi> <m:mo stretchy="false">)</m:mo> </m:mrow> </m:mrow> </m:math> s_{p}(G) . In this paper, we shall treat cases where <m:math xmlns:m="http://www.w3.org/1998/Math/MathML"> <m:mrow> <m:mrow> <m:msub> <m:mi>s</m:mi> <m:mi>p</m:mi> </m:msub> <m:mo>⁢</m:mo> <m:mrow> <m:mo stretchy="false">(</m:mo> <m:mi>G</m:mi> <m:mo stretchy="false">)</m:mo> </m:mrow> </m:mrow> <m:mo>&lt;</m:mo> <m:mrow> <m:mn>1</m:mn> <m:mo>+</m:mo> <m:mrow> <m:mn>3</m:mn> <m:mo>⁢</m:mo> <m:mi>p</m:mi> </m:mrow> <m:mo>+</m:mo> <m:mrow> <m:mn>2</m:mn> <m:mo>⁢</m:mo> <m:msup> <m:mi>p</m:mi> <m:mn>2</m:mn> </m:msup> </m:mrow> </m:mrow> </m:mrow> </m:math> s_{p}(G)&lt;1+3p+2p^{2} , and we shall determine the structure of G when <m:math xmlns:m="http://www.w3.org/1998/Math/MathML"> <m:mrow> <m:mrow> <m:msub> <m:mi>s</m:mi> <m:mi>p</m:mi> </m:msub> <m:mo>⁢</m:mo> <m:mrow> <m:mo stretchy="false">(</m:mo> <m:mi>G</m:mi> <m:mo stretchy="false">)</m:mo> </m:mrow> </m:mrow> <m:mo>≤</m:mo> <m:mrow> <m:mn>1</m:mn> <m:mo>+</m:mo> <m:mi>p</m:mi> <m:mo>+</m:mo> <m:msup> <m:mi>p</m:mi> <m:mn>2</m:mn> </m:msup> </m:mrow> </m:mrow> </m:math> s_{p}(G)\\leq 1+p+p^{2} .
How meristems shape plant architecture in cereals—Cereal Stem Cell Systems (CSCS) Consortium
2025-06-20

Abstract Meristems are major determinants of plant architecture, diversification, and acclimation to environmental stresses. Moreover, meristems play also a major role during crop domestication and are fundamentally important for the productivity of crop plants as they directly determine biomass and grain yield. While vegetative meristems shape the basic plant body plan and produce all above- and below-ground parts of plants, some vegetative meristems transit to reproductive meristems, forming sexual organs and germ cells. Most knowledge about plant meristems was generated using the model plant Arabidopsis. Compared with Arabidopsis, architecture of grass or cereals, including crops like maize, wheat, barley, rice and sorghum, is more complex: cereals produce additional organs like a coleoptile, seminal roots originating from the scutellar nodes in the embryo and shoot-borne crown roots as well as highly complex inflorescence meristems with meristem types absent in eudicots. Moreover, studies in cereals indicated that paradigms based on studies using Arabidopsis are not universally applicable. This review therefore aims to provide a comprehensive overview about the initiation, establishment, maintenance, and function of the various cereal meristems and their stem cell niches that shape our most important crop plants. Stem cell–like systems involved in leaf pattering and germline formation are also considered. The focus is also on the significant progress that has been made recently using novel tools to elucidate gene regulatory networks underlying the development and function of the various cereal meristems.
Quantification of Endogenous Steroids and Hormonal Contraceptives in Human Plasma via Surrogate Calibration and UHPLC-MS/MS
2025-06-20

Quantifying endogenous and exogenous steroids at low concentrations in biological matrices remains a major analytical challenge. Immunoassay-based diagnostics are limited by cross-reactivity, particularly at low levels, prompting a shift toward (ultra)high-performance liquid chromatography-tandem mass spectrometry ((U)HPLC-MS/MS) for clinical applications. A key limitation for endogenous hormone quantification is the absence of a true blank matrix for external calibration. To address this, we developed a surrogate calibration method employing 1,2-dimethylimidazole-5-sulfonyl chloride (DMIS) derivatization for estrogens, enabling sensitive and selective quantification alongside nonderivatized steroids. Stable isotope-labeled surrogate calibrants and internal standards were used to achieve matrix-matched quantification within a clinically relevant range. Parallelism between analytes and surrogate calibrants was systematically verified in plasma across multiple calibration levels. The method was further optimized through the use of narrow-bore UHPLC columns and refined chromatographic conditions to enhance sensitivity and resolution for a broad analyte panel. Combined with efficient protein precipitation and 96-well plate-based solid-phase extraction, the developed assay achieves pg/mL-level quantification in human plasma with high precision and accuracy. This integrated approach uniquely combines surrogate calibration for endogenous steroids with external calibration for exogenous contraceptives, including sensitive DMIS-based derivatization for estrogens, enabling comprehensive hormonal profiling in a single run. Beyond its analytical scope, the method outlines a structured validation strategy, which is aligned with regulatory principles, and may therefore serve as a practical reference for future LC-MS/MS assays employing surrogate calibration.
Luminescence dating of palaeoshoreline deposits from Khyargas Nuur, Western Mongolia: A comparative study of multigrain and single‐grain K‐feldspar dating
2025-06-20

ABSTRACT The evolution of lakes in western Mongolia and their responses to climate changes and glacial meltwater input remain poorly understood. This study evaluates the reliability of multigrain and single‐grain K‐feldspar post‐infrared infrared stimulated luminescence (IRSL) (pIRIR) dating applied to palaeoshoreline sediments at Khyargas Nuur, western Mongolia. It specifically focuses on assessing the extent of pIRIR signal bleaching and proposes an improved methodology for dating shoreline sediments where quartz is unsuitable for luminescence dating. Multigrain pIRIR signals measured at 150°C (pIRIR 150 ) and 225°C (pIRIR 225 ) were used to date Holocene and older samples, respectively. Single‐grain pIRIR dating was conducted for the first time in the region to assess bleaching conditions and refine age estimates. Our comprehensive methodological approach was essential for constructing a robust lake level chronology. Single‐grain measurements, combined with the application of the minimum age model (MAM), allowed us to identify and correct for incomplete bleaching in several samples. Notably, many of the multigrain aliquots showed no clear signs of poor bleaching in their equivalent dose ( D e ) distributions, which would have resulted in significant age overestimation if single‐grain data had not been available. Without this approach, the chronology of lake level fluctuations could have been significantly misinterpreted. By addressing this issue, we confidently date the highest lake level at ~129 m above modern lake (a.m.l) to marine isotope stage (MIS) 5 (~89 ka) and a subsequent highstand (~118 m a.m.l) to the Late Glacial (~14 ka). Following this highstand, lake levels declined rapidly (~25 m/ka), reaching ~20 m a.m.l through the Late Glacial to early Holocene transition. During the late Holocene, the palaeolake experienced a gradual regression to ~7 m a.m.l before reaching its current elevation of 1029 m above sea level (a.s.l).
Influence of maternal metabolism on neonate eating behaviour
2025-06-20

Perinatal maternal metabolism influences metabolic control in the offspring, but its impact on food intake in neonates is not known. We investigated whether ingestive behaviour in the first days of life is modulated by maternal BMI, maternal weight gain during pregnancy and by gestational diabetes (GD). Two weeks after birth, mothers of 21 neonates measured neonate food intake by weighing breast-fed babies before and after feeding, or directly in bottle-fed babies. They also filled in the Baby Eating Behaviour Questionnaire (BEBQ). We compared results between groups defined by preconceptual BMI, by pregnancy-related body weight gain according to Institute of Medicine guidelines and by GD diagnosis, and performed supplementary stepwise regression analyses. Birth weight was generally comparable between maternal groups and averaged 3450 g. BEBQ 'food responsiveness' was rated higher in neonates born to females with increased vs. reduced weight gain during pregnancy; weight gain in the second trimester of pregnancy was of particular relevance for this pattern. Neonates born to mothers with recommended weight gain displayed increased 'satiety responsiveness' compared to neonates of mothers with increased or reduced weight gain. BEBQ 'slowness in eating' was rated higher by mothers with increased vs. those with recommended weight gain in the second trimester and tended to be increased in neonates born to mothers with GD. Eating protocols supported the latter finding but in general did not yield significant group differences. We conclude that dysregulation of maternal metabolism during pregnancy may predispose neonates to dysfunctional eating behaviour at a very early age, with potential ramifications for subsequent body weight trajectories.
The effect of sensor-to-source distance on magnetic neuromuscular signals
2025-06-20

Abstract Magnetomyography (MMG) can be used as a contactless modality to study the neuromuscular system. On the one hand, being contactless is a practical advantage as there is no need to prepare skin or attach electrodes as in electromyography (EMG). On the other hand, it is also a disadvantage because the magnetic field decays with increasing distance. However, the effect of sensor-to-source distance in MMG has not been systematically studied. Comparative in vivo and in silico experiments of the effect of sensor-to-source distance were performed. In vivo, muscle activity was recorded using simultaneous surface EMG and one triaxial optically pumped magnetometer (OPM). For the simulations, an established multiscale muscle model was used to predict how distance affects the signal-to-noise ratio (SNR) and the signal’s spectral content. Given an environmental noise level of 0.5–1 pT root-mean-square (RMS) from 10 to 350 Hz, it was impossible to robustly detect muscle activity of one finger flexor muscle beyond a distance of two centimeters using OPM technology. In silico experiments showed a high SNR between 8 and 29 for MMG at 0.5 cm distance. Increasing the distance increases the MMG’s median frequency content. The simulations uncovered that this is due to the effect of noise. For distances greater than two centimeters, measuring MMG of voluntary contractions in medium-sized muscles with current OPM technology and conventional magnetic shielding cannot be recommended.
Bioinspired morphology and task curricula for learning locomotion in bipedal muscle-actuated systems
2025-06-20

Abstract Humans master complex motor skills such as walking and running through a sophisticated blend of learning and adaptation. Replicating this level of skill acquisition with traditional Reinforcement Learning (RL) methods in musculoskeletal humanoid systems is challenging due to intricate control dynamics and over-actuation. Inspired by human developmental learning, here we address these challenges, with a double curriculum approach: a three-stage task curriculum (balance, walk, run) and an up to three-stage morphology curriculum (4 year-old, 12 year-old, adult), mimicking physical growth. This combined approach enables the agent to efficiently learn robust gaits that are adaptable to varying velocities and perturbations. Extensive analysis and ablation studies demonstrate that our method outperforms state-of-the-art exploration techniques for musculoskeletal systems. Our approach is agnostic to the underlying RL algorithm and does not require reward tuning, demonstrations, or specific muscular architecture information, marking a notable advancement in the field.
Minimizing detection bias of somatic mutations in a highly heterozygous oak genome
2025-06-21

Abstract Somatic mutations are particularly relevant for long-lived organisms. Sources of somatic mutations include imperfect DNA repair, replication errors, and exogenous damage such as ultraviolet radiation. A previous study estimated a surprisingly low number of somatic mutations in a 234-year-old individual of the pedunculate oak (Quercus robur), known as the Napoleon Oak. It has been suggested that the true number of somatic mutations was underestimated due to gaps in the reference genome and too conservative filtering of potential mutations. We therefore generated new high-fidelity long-read data for the Napoleon Oak (n = 12) to produce both a pseudo-haploid genome assembly and a partially phased diploid assembly. The high heterozygosity allowed for complete reconstruction of phased and gapless centromeres for 22 of the 24 chromosomes. On the other hand, the high heterozygosity posed challenges for short-read alignments. Use of only the pseudo-haploid assembly as a reference led to potential misalignments, while use of only the diploid assembly reduced variant detection sensitivity. Since most somatic mutations are layer-specific, the fraction of reads covering a specific somatic mutation is expected to be relatively low, even where all cells in a single layer contain a specific mutation. To address this challenge, we employed a read assignment strategy, selecting the appropriate reference sequence (pseudo-haploid or diploid) based on alignment score and mapping quality. Ultimately, we identified 198 high-confidence somatic mutations, compared with 17 somatic mutations identified before with the same set of short reads. Our approach thus increased the total estimated annual mutation rate by a factor of 5.
Selbstverständigung, Selbsterkenntnis und Religion
2025-06-21

Abstract In recent years, there have been several noteworthy attempts to understand Hegel’s doctrine of “absolute spirit” as a theory of cultural practices in which human self-understanding is formed, cultivated, and critically examined. This essay explores a number of theologically significant conclusions that can be drawn from this assumption. In doing so, I address central questions concerning the subject, content, and goals of the practice. My main thesis is that, for Hegel, there is a complex interplay between religious or metaphysical beliefs about the structure of reality as a whole and the successful formation of self-knowledge. In particular, these relations form an important basis for the critical evaluation of the cultural practices themselves and their social dimensions. I argue that these characteristics tend to be overlooked in contemporary interpretations.
GRK-biased adrenergic agonists for the treatment of type 2 diabetes and obesity
2025-06-23

Biased agonism of G protein-coupled receptors (GPCRs) offers potential for safer medications. Current efforts have explored the balance between G proteins and β-arrestin; however, other transducers like GPCR kinases (GRKs) remain understudied. GRK2 is essential for β<sub>2</sub> adrenergic receptor (β<sub>2</sub>AR)-mediated glucose uptake, but β<sub>2</sub>AR agonists are considered poor clinical candidates for glycemic management due to G<sub>s</sub>/cyclic AMP (cAMP)-induced cardiac side effects and β-arrestin-dependent desensitization. Using ligand-based virtual screening and chemical evolution, we developed pathway-selective agonists of β<sub>2</sub>AR that prefer GRK coupling. These compounds perform well in preclinical models of hyperglycemia and obesity and demonstrate a lower potential for cardiac and muscular side effects compared with standard β<sub>2</sub>-receptor agonists and incretin mimetics, respectively. Furthermore, the lead candidate showed favorable pharmacokinetics and was well tolerated in a placebo-controlled clinical trial. GRK-biased β<sub>2</sub>AR partial agonists are thus promising oral alternatives to injectable incretin mimetics used in the treatment of type 2 diabetes and obesity.
Robustness and Cybersecurity in the EU Artificial Intelligence Act
2025-06-23

The EU Artificial Intelligence Act (AIA) establishes different legal principles for different types of AI systems. While prior work has sought to clarify some of these principles, little attention has been paid to robustness and cybersecurity. This paper aims to fill this gap. We identify legal challenges and shortcomings in provisions related to robustness and cybersecurity for high-risk AI systems(Art. 15 AIA) and general-purpose AI models (Art. 55 AIA). We show that robustness and cybersecurity demand resilience against performance disruptions. Furthermore, we assess potential challenges in implementing these provisions in light of recent advancements in the machine learning (ML) literature. Our analysis informs efforts to develop harmonized standards, guidelines by the European Commission, as well as benchmarks and measurement methodologies under Art. 15(2) AIA. With this, we seek to bridge the gap between legal terminology and ML research, fostering a better alignment between research and implementation efforts.
Foveal neurons of the monkey superior colliculus signal trans-saccadic prediction errors
2025-06-23

Across saccades, neurons in retinotopically organized visual representations experience drastically different images, but visual percepts remain stable. Here we investigated whether such stability can be mediated, in part, via prediction-error signaling by neurons processing post-saccadic visual images. We specifically recorded from foveal superior colliculus (SC) neurons when a visual image only overlapped with their response fields (RF’s) after foveating saccades but not pre-saccadically. When we rapidly changed the target features intra-saccadically, the foveal neurons’ post-saccadic visual reafferent responses were elevated, even though the neurons did not directly sample the pre-saccadic extrafoveal target features. This effect did not occur in the absence of saccades, and it also scaled with the extent of the introduced intra-saccadic image feature discrepancies. These results suggest that foveal SC neurons may signal a trans-saccadic prediction error when the foveated image stimulating them is inconsistent with that expected from pre-saccadic extrafoveal representations, a potential perceptual stability mechanism.