bluuebunny/crossref_metadata_2025 huggingface dataset:
Lexical be
Authors: Miller Philip , Culicover Peter W.
Published: January 2025

We explore the surprising lexical be construction in English (e.g. Why don’t you be quiet?). After an overview of previous discussions, an investigation of the use of lexical be in the COCA and SOAP corpora is provided. It is shown that its distribution is highly skewed and that it is completely felicitous only under a very limited set of conditions. An account of lexical be is then provided showing that the conditions that license it are inherited from more general constructions, most importantly the negative imperative construction and the ‘Why don’t you’ construction. In this light, it is suggested that the lexical be construction, with its special properties, provides strong evidence for a constructional approach to linguistic competence along the lines of Goldberg (1995), Culicover and Jackendoff (2005), Sag (2012).
Review Essay: Postanthropocentric Political Theories
Authors: Biro Andrew
Published: January 2025

At least since Aristotle defined human beings as “political animals,” politics in the Western tradition has largely been defined in anthropocentric terms. Politics was a realm of distinctively human endeavors, while nonhuman nature remained outside. Nature might impinge on or set limits to political action, but was conceived as constitutively outside of politics. However else nonhuman entities might engage with humans or each other, these relations or engagements were not understood as political. Until quite recently, Western political theory was decidedly anthropocentric. The rise of environmental problematics, and particularly the political salience of the global climate crisis, however, have made the idea of a constitutive separation between (nonhuman) nature and (human) politics less tenable. Not only the material manipulation of the nonhuman world, but also its conceptual framing, are increasingly understood as political projects.1 At the same time, Western political thought has become increasingly open to non-Western cosmologies that do not posit a rigid divide between human and non- (or more-than-) human worlds. Environmental (or green) political theory has become an increasingly robust subdiscipline,2 and political theory, like a number of other humanities disciplines, has undergone an “animal turn.”3 Three of the four recent books under consideration form part of this latter animal turn while Sharon Krause’s Eco-Emancipation is firmly situated in the field of environmental political theory.
Make One for the Team: Culture Wars and Group-Serving Pronatalism
Authors: Perry Samuel L. , Grubbs Joshua B.
Published: January 2025

What undergirds the association between religious and political conservatism and “group-serving pronatalism”; that is, support for childbearing to advance social or political goals rather than for personal fulfillment? Although recent research suggests that Christian nationalism—reflecting a desire to formally privilege conservative Christian values and identity—strongly accounts for the link, previous studies have not inquired about specific group-serving reasons to have children. Analyses of nationally representative data affirm Christian nationalism (measured in two ways) as the strongest predictor of support for group-serving pronatalism; specifically, support for having children to reverse the nation’s declining fertility, perpetuate one’s religious or racial heritage, and secure influence for one’s political group. These associations are weakly or inconsistently moderated by indicators of traditionalism, conservatism, and race. Findings affirm support for having children to advance national, religious, racial, or political goals corresponds strongly with a desire to privilege a Christian national identity and social order.
Early Validation of High-Level System Requirements with Event Calculus and Answer Set Programming
Authors: VAŠÍČEK ONDŘEJ , ARIAS JOAQUIN , FIEDOR JAN , GUPTA GOPAL , HALL BRENDAL , KŘENA BOHUSLAV , LARSON BRIAN , VARANASI SARAT CHANDRA , VOJNAR TOMÁŠ
Published: January 2025

This paper proposes a new methodology for early validation of high-level requirements on cyber-physical systems with the aim of improving their quality and, thus, lowering chances of specification errors propagating into later stages of development where it is much more expensive to fix them. The paper presents a transformation of a real-world requirements specification of a medical device—the Patient-Controlled Analgesia (PCA) Pump—into an Event Calculus model that is then evaluated using Answer Set Programming and the s(CASP) system. The evaluation under s(CASP) allowed deductive as well as abductive reasoning about the specified functionality of the PCA pump on the conceptual level with minimal implementation or design dependent influences and led to fully automatically detected nuanced violations of critical safety properties. Further, the paper discusses scalability and non-termination challenges that had to be faced in the evaluation and techniques proposed to (partially) solve them. Finally, ideas for improving s(CASP) to overcome its evaluation limitations that still persist as well as to increase its expressiveness are presented.
Symbolic Parameter Learning in Probabilistic Answer Set Programming
Authors: AZZOLINI DAMIANO , GENTILI ELISABETTA , RIGUZZI FABRIZIO
Published: January 2025

Parameter learning is a crucial task in the field of Statistical Relational Artificial Intelligence: given a probabilistic logic program and a set of observations in the form of interpretations, the goal is to learn the probabilities of the facts in the program such that the probabilities of the interpretations are maximized. In this paper, we propose two algorithms to solve such a task within the formalism of Probabilistic Answer Set Programming, both based on the extraction of symbolic equations representing the probabilities of the interpretations. The first solves the task using an off-the-shelf constrained optimization solver while the second is based on an implementation of the Expectation Maximization algorithm. Empirical results show that our proposals often outperform existing approaches based on projected answer set enumeration in terms of quality of the solution and in terms of execution time.
Reasoning About Study Regulations in Answer Set Programming
Authors: HAHN SUSANA , SCHAUB TORSTEN , MARTENS CEDRIC , NEMES AMADE , OTUNUYA HENRY , ROMERO JAVIER , SCHELLHORN SEBASTIAN
Published: January 2025

We are interested in automating reasoning with and about study regulations, catering to various stakeholders, ranging from administrators, over faculty, to students at different stages. Our work builds on an extensive analysis of various study programs at the University of Potsdam. The conceptualization of the underlying principles provides us with a formal account of study regulations. In particular, the formalization reveals the properties of admissible study plans. With these at end, we propose an encoding of study regulations in Answer Set Programming that produces corresponding study plans. Finally, we show how this approach can be extended to a generic user interface for exploring study plans.
Nanolite Crystallization in Volcanic Glasses: Insights From High‐Temperature Raman Spectroscopy and Low‐Temperature Rock‐Magnetic Analysis
Authors: Bondar Dmitry , Canizarès Aurèlien , Bilardello Dario , Valdivia Pedro , Zandonà Alessio , Romano Claudia , Allix Mathieu , Di Genova Danilo
Published: January 2025

High‐temperature Raman spectroscopy offers a cost‐effective alternative to extensive infrastructure and sensitive instrumentation for investigating nanolite crystallization in undercooled volcanic melts, a key area of interest in volcanology. This study examined nanolite formation in anhydrous andesite melts in situ at high temperatures, identifying distinct Raman peaks at 310 and 670 cm−1 appearing above the glass transition temperature. The initial amorphous glass remained stable up to 655°C, beyond which Fe‐Ti‐oxide nanolites progressively formed at higher temperatures, as also confirmed by complementary XRD analysis. The evolution of the 310 cm−1 peak depends only on the magnitude of nanolite crystallization, while the intensity of the 670 cm−1 peak is temperature‐dependent and challenging to observe above 500°C. Complementary low‐temperature rock‐magnetic analyses confirmed Fe‐Ti‐oxide nanocrystallization with nanolites around 20 nm in diameter. The study tested lasers of different wavelengths (from 355 to 514 nm) and found the green laser to be the most effective for collecting spectra at both room and high temperature. However, above 720°C, black body radiation significantly hinders Raman observation with the green laser when using a non‐confocal setup and analyzing poorly transparent samples. If higher temperature measurements are desired, switching to a confocal setup and using lower wavelength lasers should be considered. This research offers a protocol for studying nanolite formation and melt dynamics at high temperatures, providing a foundation for future studies of volcanic processes.
Reactivation of a Subglacial Channel Around the Grounding Zone of Roi Baudouin Ice Shelf, Antarctica
Authors: Zhou Yan , Franke Steven , Kleiner Thomas , Drews Reinhard , Humbert Angelika , Jansen Daniela , Steinhage Daniel , Eisen Olaf
Published: January 2025

Subglacial water beneath the Antarctic Ice Sheet is often funneled via subglacial channels, which inject freshwater into ice‐shelf cavities where it interacts with ocean water. The temporal variability of this system has been poorly observed, but its importance for ice dynamics is well recognized. Airborne radar data show a subglacial channel evolving within a decade near of the grounding zone of the Roi Baudouin Ice Shelf (East Antarctica), while topographic signatures on the ice shelf indicate prior inactivity for 60 years. Combining our observations with subglacial hydrological modeling, we suggest that the interplay between episodic subglacial water pulses and ocean water intrusion drive the opening and closing of the channels. Our findings illuminate the short‐term transient nature of subglacial channel activity. This impacts ice‐shelf–ocean processes, which are important for constraining increasing ocean warming onto ice‐shelf basal mass balance, but pose significant challenges for subglacial hydrological modeling at the grounding zone.
Xenolith Constraints on the Mantle Potential Temperature and Thickness of Cratonic Roots Through Time
Authors: Sudholz Z. J. , Copley A.
Published: January 2025

The temperature of the convecting mantle and thickness of the lithosphere control many of Earth's processes. However, there is disagreement regarding the evolution of these quantities through time. We use a global data set of mantle xenoliths and xenocrysts to construct paleogeotherms at different eruption ages (16–1,311 Ma) and estimate the temperature and depth of the lithosphere‐asthenosphere boundary (LAB) as a function of mantle potential temperature (Tp). We find that the maximum pressure and temperature (PT) of xenoliths matches the modeled LAB conditions when a Tp of 1,315°C is used. At higher Tp (1,450–1,550) we observe a gap between the maximum PT of xenoliths and the LAB conditions. Because this gap systematically increases with Tp, and the maximum PT of xenoliths has not changed over time, we suggest that there has actually been only minor (<50°C) changes in mantle Tp since the Meso‐Proterozoic.
Impact of Atmospheric Stability on Swell‐Induced Perturbations in Wave Boundary Layer
Authors: Gao Tianhai , Feng Xingru , Xie Jianbin , Li Jinyuan , Yin Baoshu
Published: January 2025

Wind stress deviates both in magnitude and direction under light wind conditions due to the modulation effect of swell waves. Eddy covariance flux measurements were conducted from an offshore wind tower in the northern South China Sea to investigate the influence of swell‐induced perturbations on the evolution of wind velocity fluctuations and wind stress reductions. Direct evidence of the wind field being affected by dominant swell waves was observed at an observational height of 20 m, indicating that swell‐induced perturbations can penetrate the wave boundary layer to at least this height. Time series analysis implies that a stable atmosphere helps preserve the observed prominent peak in wind velocity spectra, extending it to a higher range under large wave age. Therefore, swell‐induced perturbations are more easily observed at night. Additionally, our results show that swell wave modulation on wind stress is not merely restricted to moments with pronounced peaks in velocity spectra, indicating that wind stress reduction is not an exception. The most significant reduction occurs at wind speeds around 2–4 m/s, leading to negative wind stress, which implies momentum transfer from the ocean to the atmosphere. Our conclusion illustrates that the deviation of wind stress magnitude increases under stable atmospheric conditions; however, with a simple correction model, the modified wind stress is comparable to the observed values.
Derivation and Implementation of a Non‐Local Term to Improve the Oceanic Convection Representation Within the k–ɛ Parameterization
Authors: Legay Alexandre , Deremble Bruno , Burchard Hans
Published: January 2025

The representation of turbulent fluxes during oceanic convective events is important to capture the evolution of the oceanic mixed layer. To improve the accuracy of turbulent fluxes, we examine the possibility of adding a non‐local component in their expression in addition to the usual downgradient part. To do so, we extend the – algebraic second‐moment closure by relaxing the assumption on the equilibrium of the temperature variance . With this additional evolution equation for the temperature variance, we obtain a –– model (the “” model) which includes a non‐local term for the temperature flux. We validate this new model against Large Eddy Simulations (LES) in three test cases: free convection (FC), wind‐driven mixing, and diurnal cycle (DC). For wind‐driven mixing, is equivalent to –. However, in the presence of a buoyancy flux (FC and DC), we find that the vertical profile of temperature of the LES is better captured by than –. Particularly, the non‐local term increases the fraction of the mixed layer that is stably stratified. For FC, this fraction is near 50% for both and the LES, whereas the – value is 20%. We show that this improvement is due to a better representation of the temperature variance in the inner part of the mixed layer. This better representation is mainly caused by the diffusion of temperature variance, which is described by and not by –.
Unique C‐Ring Methylated Hopene Biomarkers in a Paleocene Lake
Authors: Naafs B. David A.
Published: January 2025

Hopanoids are bacterial lipids that are ubiquitous on the surface of the Earth and in the sedimentary record. Hopanoids with an extra methyl group located in the A‐ring (at the C‐2 or C‐3 position) of the carbon skeleton are well known and these 2‐ or 3‐methylhopanoids have been used to infer specific biogeochemical or environmental conditions in the geological past, including the Paleogene. However, hopanoids with additional methylations outside the A‐ring and/or more than one additional methylation in their pentacyclic ring system are rare. This paper reports the occurrence of hop‐17(21)‐enes methylated in the C‐ring (tentatively assigned to the C‐12 position) and dimethylated hop‐17(21)‐enes with methylations at both C‐3 (A‐ring) and C‐12 (C‐ring) in sediments from the Boltysh Core, Ukraine, that represents an early Paleocene (∼65 Myr) lake system. These (di)methyl hop‐17(21)‐enes are 1–2 orders of magnitude more abundant compared to regular hopanes in some samples. The occurrence of these unique hopanoids suggests abnormal environmental conditions during their deposition, likely attributable to volatile ecosystems in the aftermath of the Cretaceous ‐ Paleogene boundary extinction and/or the environmental stressors associated with the lower C29n hyperthermal (65.3 Myr) that is recorded in this section.
GestaltGAN: synthetic photorealistic portraits of individuals with rare genetic disorders
Authors: Kirchhoff Aron , Hustinx Alexander , Javanmardi Behnam , Hsieh Tzung-Chien , Brand Fabian , Hellmann Fabio , Mertes Silvan , André Elisabeth , Moosa Shahida , Schultz Thomas , Solomon Benjamin D. , Krawitz Peter
Published: January 2025

The facial gestalt (overall facial morphology) is a characteristic clinical feature in many genetic disorders that is often essential for suspecting and establishing a specific diagnosis. Therefore, publishing images of individuals affected by pathogenic variants in disease-associated genes has been an important part of scientific communication. Furthermore, medical imaging data is also crucial for teaching and training deep-learning models such as GestaltMatcher. However, medical data is often sparsely available, and sharing patient images involves risks related to privacy and re-identification. Therefore, we explored whether generative neural networks can be used to synthesize accurate portraits for rare disorders. We modified a StyleGAN architecture and trained it to produce artificial condition-specific portraits for multiple disorders. In addition, we present a technique that generates a sharp and detailed average patient portrait for a given disorder. We trained our GestaltGAN on the 20 most frequent disorders from the GestaltMatcher database. We used REAL-ESRGAN to increase the resolution of portraits from the training data with low-quality and colorized black-and-white images. To augment the model’s understanding of human facial features, an unaffected class was introduced to the training data. We tested the validity of our generated portraits with 63 human experts. Our findings demonstrate the model’s proficiency in generating photorealistic portraits that capture the characteristic features of a disorder while preserving patient privacy. Overall, the output from our approach holds promise for various applications, including visualizations for publications and educational materials and augmenting training data for deep learning.
Understanding the spread of agriculture in the Western Mediterranean (6th-3rd millennia BC) with Machine Learning tools
Authors: Castiello Maria Elena , Russo Emmanuele , Martínez-Grau Héctor , Jesus Ana , Prats Georgina , Antolín Ferran
Published: January 2025

The first Neolithic farmers arrived in the Western Mediterranean area from the East. They established settlements in coastal areas and over time migrated to new environments, adapting to changing ecological and climatic conditions. While farming practices and settlements in the Western Mediterranean differ greatly from those known in the Eastern Mediterranean and central Europe, the extent to which these differences are connected to the local environment and climate is unclear. Here, we tackle this question by compiling data and proxies at a superregional and multi-scale level, including archaeobotanical information, radiocarbon dates and paleoclimatic models, then applying a machine learning approach to investigate the impact of ecological and climatic constraints on the first Neolithic humans and crops. This approach facilitates calculating the pace of spread of farming in the Western Mediterranean area, modelling and estimating the potential areas suitable for settlement location, and discriminating distinct types of crop cultivation under changing climatic conditions that characterized the period 5900 – 2300 cal. BC. The results of this study shed light onto the past climate variability and its influence on human distribution in the Western Mediterranean area, but also discriminate sensitive parameters for successful agricultural practices.
Pervasive glacier retreats across Svalbard from 1985 to 2023
Authors: Li Tian , Hofer Stefan , Moholdt Geir , Igneczi Adam , Heidler Konrad , Zhu Xiao Xiang , Bamber Jonathan
Published: January 2025

A major uncertainty in predicting the behaviour of marine-terminating glaciers is ice dynamics driven by non-linear calving front retreat, which is poorly understood and modelled. Using 124919 calving front positions for 149 marine-terminating glaciers in Svalbard from 1985 to 2023, generated with deep learning, we identify pervasive calving front retreats for non-surging glaciers over the past 38 years. We observe widespread seasonal cycles in calving front position for over half of the glaciers. At the seasonal timescale, peak retreat rates exhibit a several-month phase lag, with changes on the west coast occurring before those on the east coast, coincident with regional ocean warming. This spatial variability in seasonal patterns is linked to different timings of warm ocean water inflow from the West Spitsbergen Current, demonstrating the dominant role of ice-ocean interaction in seasonal front changes. The interannual variability of calving front retreat shows a strong sensitivity to both atmospheric and oceanic warming, with immediate responses to large air and ocean temperature anomalies in 2016 and 2019, likely driven by atmospheric blocking that can influence extreme temperature variability. With more frequent blocking occurring and continued regional warming, future calving front retreats will likely intensify, leading to more significant glacier mass loss.
Construction of N−E bonds via Lewis acid-promoted functionalization of chromium-dinitrogen complexes
Authors: Yin Zhu-Bao , Wang Gao-Xiang , Yan Xuechao , Wei Junnian , Xi Zhenfeng
Published: January 2025

Direct conversion of dinitrogen (N2) into N-containing compounds beyond ammonia under ambient conditions remains a longstanding challenge. Herein, we present a Lewis acid-promoted strategy for diverse nitrogen-element bonds formation from N2 using chromium dinitrogen complex [Cp*(I
i
Pr2Me2)Cr(N2)2]K (1). With the help of Lewis acids AlMe3 and BF3, we successfully trap a series of fleeting diazenido intermediates and synthesize value-added compounds containing N−B, N−Ge, and N−P bonds with 3 d metals, offering a method for isolating unstable intermediates. Furthermore, the formation of N−C bonds is realized under more accessible conditions that avoid undesired side reactions. DFT calculations reveal that Lewis acids enhance the participation of dinitrogen units in the frontier orbitals, thereby promoting electrophilic functionalization. Moreover, Lewis acid replacement and a base-induced end-on to side-on switch of [NNMe] unit in [(Cp*(I
i
Pr2Me2)CrNN(BEt3)(Me)] (8) are achieved.
The effectiveness of TRIS and ammonium buffers in glass dissolution studies: a comparative analysis
Authors: Ravikumar Ramya , Thorpe Clare L. , Corkhill Claire L. , Walling Sam A. , Neeway James J. , Pearce Carolyn I. , Kruger Albert A. , Kosson David S. , Marcial Jose , Hand Russell J.
Published: January 2025

Selecting appropriate buffers is crucial for evaluating the chemical durability of glass under controlled conditions such as in the EPA 1313 test designed to measure elemental release as a function of pH. The efficacy of two alkali-metal free buffers, TRIS (NH2C(CH2OH)3) and ammonium chloride—ammonia (NH3/NH4Cl), was investigated during EPA 1313 testing of a simulated Hanford low-activity waste borosilicate glass in the alkaline regime (pH 8.5–10.5) at varying temperatures (RT, 40 °C, and 60 °C). While both buffers maintained the desired pH at room temperature, and up to 40 °C, the effectiveness of TRIS decreased at elevated temperatures, particularly at pH 10.5. Although 11B NMR showed evidence of TRIS-B complexation, its effect on the rate of elemental release was found to be negligible under the test conditions. With ammonium buffer, the release of alkali cations was slightly elevated when compared to the same conditions with TRIS at early time points.
A synthetic cyclic peptide for promoting antigen presentation and immune activation
Authors: Zhang Jiahui , Madge Harrison Y. R. , Mahmoud Asmaa , Lu Lantian , Wang Wanyi , Huang Wenbin , Koirala Prashamsa , Gonzalez Cruz Jazmina L. , Kong Wei Yang , Bashiri Sahra , Shalash Ahmed O. , Hussein Waleed M. , Khalil Zeinab G. , Wells James W. , Toth Istvan , Stephenson Rachel J.
Published: January 2025

Cyclic peptides are often used as scaffolds for the multivalent presentation of drug molecules due to their structural stability and constrained conformation. We identified a cyclic deca-peptide incorporating lipoamino acids for delivering T helper and B cell epitopes against group A Streptococcus (GAS), eliciting robust humoral immune responses. In this study, we assessed the function-immunogenicity relationship of the multi-component vaccine candidate (referred to as VC-13) to elucidate a mechanism of action. We identified a potential universal delivery platform, not only capable of adjuvanting different peptide epitopes (e.g., NS1 and 88/30 from group A Streptococcus, gonadotropin hormone releasing hormone [GnRH]), but also protein antigens (e.g., bovine serum albumin [BSA], receptor binding domain (RBD) of the SARS-CoV-2 protein responsible for COVID-19 infection [SARS-CoV-2 RBD]) and small molecular haptens (e.g., cocaine). All vaccine candidates self-assembled into sub-500 nm nanoparticles and induced high antigen-specific systemic IgG titers and opsonic potential compared to the antigen co-administered with a commercial adjuvant, complete Freund’s adjuvant. Notably, presence of the cyclic decapeptide in this vaccine increased accumulation in the draining inguinal lymph nodes, facilitating cellular uptake of peptide antigens. Furthermore, the lipoamino acid promoted dendritic cell activation, acting as both toll-like receptors 2 and 4 -targeting moiety. Our study revealed the importance of the cyclic decapeptide and lipoamino acid presence in antigen presentation and immune response activation, leading onto the development of a fully synthetic, self-assembled, and promising platform for the delivery of subunit vaccines and anti-drug vaccines.
Continental influx and pervasive matrilocality in Iron Age Britain
Authors: Cassidy Lara M. , Russell Miles , Smith Martin , Delbarre Gabrielle , Cheetham Paul , Manley Harry , Mattiangeli Valeria , Breslin Emily M. , Jackson Iseult , McCann Maeve , Little Harry , O’Connor Ciarán G. , Heaslip Beth , Lawson Daniel , Endicott Phillip , Bradley Daniel G.
Published: January 2025

Roman writers found the relative empowerment of Celtic women remarkable1. In southern Britain, the Late Iron Age Durotriges tribe often buried women with substantial grave goods2. Here we analyse 57 ancient genomes from Durotrigian burial sites and find an extended kin group centred around a single maternal lineage, with unrelated (presumably inward migrating) burials being predominantly male. Such a matrilocal pattern is undescribed in European prehistory, but when we compare mitochondrial haplotype variation among European archaeological sites spanning six millennia, British Iron Age cemeteries stand out as having marked reductions in diversity driven by the presence of dominant matrilines. Patterns of haplotype sharing reveal that British Iron Age populations form fine-grained geographical clusters with southern links extending across the channel to the continent. Indeed, whereas most of Britain shows majority genomic continuity from the Early Bronze Age to the Iron Age, this is markedly reduced in a southern coastal core region with persistent cross-channel cultural exchange3. This southern core has evidence of population influx in the Middle Bronze Age but also during the Iron Age. This is asynchronous with the rest of the island and points towards a staged, geographically granular absorption of continental influence, possibly including the acquisition of Celtic languages.
Prolonged persistence of mutagenic DNA lesions in somatic cells
Authors: Spencer Chapman Michael , Mitchell Emily , Yoshida Kenichi , Williams Nicholas , Fabre Margarete A. , Ranzoni Anna Maria , Robinson Philip S. , Kregar Lori D. , Wilk Matthias , Boettcher Steffen , Mahbubani Krishnaa , Saeb Parsy Kourosh , Gowers Kate H. C. , Janes Sam M. , Ng Stanley W. K. , Hoare Matt , Green Anthony R. , Vassiliou George S. , Cvejic Ana , Manz Markus G. , Laurenti Elisa , Martincorena Iñigo , Stratton Michael R. , Nangalia Jyoti , Coorens Tim H. H. , Campbell Peter J.
Published: January 2025

DNA is subject to continual damage, leaving each cell with thousands of individual DNA lesions at any given moment1–3. The efficiency of DNA repair means that most known classes of lesion have a half-life of minutes to hours3,4, but the extent to which DNA damage can persist for longer durations remains unknown. Here, using high-resolution phylogenetic trees from 89 donors, we identified mutations arising from 818 DNA lesions that persisted across multiple cell cycles in normal human stem cells from blood, liver and bronchial epithelium5–12. Persistent DNA lesions occurred at increased rates, with distinctive mutational signatures, in donors exposed to tobacco or chemotherapy, suggesting that they can arise from exogenous mutagens. In haematopoietic stem cells, persistent DNA lesions, probably from endogenous sources, generated the characteristic mutational signature SBS1913; occurred steadily throughout life, including in utero; and endured for 2.2 years on average, with 15–25% of lesions lasting at least 3 years. We estimate that on average, a haematopoietic stem cell has approximately eight such lesions at any moment in time, half of which will generate a mutation with each cell cycle. Overall, 16% of mutations in blood cells are attributable to SBS19, and similar proportions of driver mutations in blood cancers exhibit this signature. These data indicate the existence of a family of DNA lesions that arise from endogenous and exogenous mutagens, are present in low numbers per genome, persist for months to years, and can generate a substantial fraction of the mutation burden of somatic cells.
Autoactive CNGC15 enhances root endosymbiosis in legume and wheat
Authors: Cook Nicola M. , Gobbato Giulia , Jacott Catherine N. , Marchal Clemence , Hsieh Chen Yun , Lam Anson Ho Ching , Simmonds James , del Cerro Pablo , Gomez Pilar Navarro , Rodney Clemence , Cruz-Mireles Neftaly , Uauy Cristobal , Haerty Wilfried , Lawson David M. , Charpentier Myriam
Published: January 2025

Nutrient acquisition is crucial for sustaining life. Plants develop beneficial intracellular partnerships with arbuscular mycorrhiza (AM) and nitrogen-fixing bacteria to surmount the scarcity of soil nutrients and tap into atmospheric dinitrogen, respectively1,2. Initiation of these root endosymbioses requires symbiont-induced oscillations in nuclear calcium (Ca2+) concentrations in root cells3. How the nuclear-localized ion channels, cyclic nucleotide-gated channel (CNGC) 15 and DOESN’T MAKE INFECTIONS1 (DMI1)4 are coordinated to specify symbiotic-induced nuclear Ca2+ oscillations remains unknown. Here we discovered an autoactive CNGC15 mutant that generates spontaneous low-frequency Ca2+ oscillations. While CNGC15 produces nuclear Ca2+ oscillations via a gating mechanism involving its helix 1, DMI1 acts as a pacemaker to specify the frequency of the oscillations. We demonstrate that the specificity of symbiotic-induced nuclear Ca2+ oscillations is encoded in its frequency. A high frequency activates endosymbiosis programmes, whereas a low frequency modulates phenylpropanoid pathways. Consequently, the autoactive cngc15 mutant, which is capable of generating both frequencies, has increased flavonoids that enhance AM, root nodule symbiosis and nutrient acquisition. We transferred this trait to wheat, resulting in field-grown wheat with increased AM colonization and nutrient acquisition. Our findings reveal a new strategy to boost endosymbiosis in the field and reduce inorganic fertilizer use while sustaining plant growth.
Massively parallel characterization of transcriptional regulatory elements
Authors: Agarwal Vikram , Inoue Fumitaka , Schubach Max , Penzar Dmitry , Martin Beth K. , Dash Pyaree Mohan , Keukeleire Pia , Zhang Zicong , Sohota Ajuni , Zhao Jingjing , Georgakopoulos-Soares Ilias , Noble William S. , Yardımcı Galip Gürkan , Kulakovskiy Ivan V. , Kircher Martin , Shendure Jay , Ahituv Nadav
Published: January 2025

The human genome contains millions of candidate cis-regulatory elements (cCREs) with cell-type-specific activities that shape both health and many disease states1. However, we lack a functional understanding of the sequence features that control the activity and cell-type-specific features of these cCREs. Here we used lentivirus-based massively parallel reporter assays (lentiMPRAs) to test the regulatory activity of more than 680,000 sequences, representing an extensive set of annotated cCREs among three cell types (HepG2, K562 and WTC11), and found that 41.7% of these sequences were active. By testing sequences in both orientations, we find promoters to have strand-orientation biases and their 200-nucleotide cores to function as non-cell-type-specific ‘on switches’ that provide similar expression levels to their associated gene. By contrast, enhancers have weaker orientation biases, but increased tissue-specific characteristics. Utilizing our lentiMPRA data, we develop sequence-based models to predict cCRE function and variant effects with high accuracy, delineate regulatory motifs and model their combinatorial effects. Testing a lentiMPRA library encompassing 60,000 cCREs in all three cell types further identified factors that determine cell-type specificity. Collectively, our work provides an extensive catalogue of functional CREs in three widely used cell lines and showcases how large-scale functional measurements can be used to dissect regulatory grammar.
Self-isolation of adolescents after Covid-19 pandemic between social withdrawal and Hikikomori risk in Italy
Authors: Cerbara Loredana , Ciancimino Giulia , Corsetti Gianni , Tintori Antonio
Published: January 2025

Social withdrawal is a widespread phenomenon among adolescents, presenting significant challenges in understanding its aetiology and dynamics. This study, drawing on data from two cross-sectional surveys conducted in 2019 and 2022 on students in public upper secondary schools, investigates the trend of self-isolation among Italian adolescents before and after the COVID-19 pandemic. The two nationally representative samples comprise 3273 and 4288 participants, respectively, with 46.3% and 41.2% identifying as female, ranging in age from 14 to 19 years. Using Multiple Correspondence Analysis (MCA) and Hierarchical Cluster Analysis (HCA), three distinct profiles of social withdrawal were identified among adolescents: “Social Butterflies”, “Friendship-Centric”, and “Lone Wolves”. Notably, the discovery of a subgroup within the Lone Wolves, composed of adolescents who never meet their friends and whose number has doubled post-pandemic, highlights the chronic nature of the phenomenon that demands urgent intervention. These findings shed light on the increase of self-isolation in Italy, showing the interplay of socio-demographic, psychological, and sociological factors underlying this phenomenon.
Validation of mixed reality in planning orbital reconstruction with patient-specific implants
Authors: Dubron K. , Shaheen E. , Jacobs R. , Politis C. , Willaert R.
Published: January 2025

This study aims to evaluate and compare the usability and performance of mixed reality (MR) technology versus conventional methods for preoperative planning of patient-specific reconstruction plates for orbital fractures. A crossover study design was used to compare MR technology with conventional three-dimensional (3D) printing approaches in the planning of maxillofacial traumatology treatments. The primary focus was on user-friendliness and the accuracy of patient-specific reconstruction planning. Secondary outcomes included investigating time differences between the two approaches and evaluating the potential effects on the learning curve. Participants were asked to complete questionnaires assessing various aspects, such as visualization, interaction, segmentation, treatment planning, and evaluation. Objective endpoints were evaluated blindly, while subjective endpoints were analyzed through a double-blind process. The total workflow time for MR technology was significantly shorter compared to the conventional method. Moreover, treatment planning using MR was significantly more accurate (p = .028), with participants reporting a higher mean global satisfaction score compared to the conventional group (80.6% vs. 72.5%). This study sheds light on the potential benefits of employing MR technology in maxillofacial orbital reconstruction. This preoperative method allows for faster and more precise design of patient-specific implants for orbital reconstruction, potentially leading to improved long-term cost-effectiveness.
Implications for the diagnosis of aspiration and aspergillosis in critically ill patients with detection of galactomannan in broncho-alveolar lavage fluids
Authors: Dubler Simon , Etringer Michael , Lichtenstern Christoph , Brenner Thorsten , Zimmermann Stefan , Schnitzler Paul , Budeus Bettina , Rengier Fabian , Kalinowska Paulina , Hoo Yuan Lih , Weigand Markus A.
Published: January 2025

Invasive infections with Aspergillus fumigatus in ICU patients are linked to high morbidity and mortality. Diagnosing invasive pulmonary aspergillosis (IPA) in non-immunosuppressed patients is difficult, as Aspergillus antigen (galactomannan [GM]) may have other causes. This retrospective study analyzed 160 ICU surgical patients with positive GM in broncho-alveolar lavage fluid (BALF), classifying them based on AspICU criteria for suspected IPA (pIPA) or aspiration. Patients with pIPA had higher disease severity than those with aspiration, including higher dialysis rates, organ transplantation, corticosteroid use, and Sequential Organ Failure Assessment (SOFA) score. Aspergillus culture was positive in 47.0% of pIPA cases but only 2.6% of aspiration cases (p < 0.001). SOFA score at first positive GM in BALF independently predicted 28-day mortality. In surgical patients with a positive GM in BALF, aspiration is more likely if there’s no corticosteroid therapy, negative Aspergillus culture, and a history of aspiration events. Diagnosis of pIPA requires Aspergillus culture or prior corticosteroid therapy in this cohort of critically ill patients.
Intranasally administrated fusion-inhibitory lipopeptides block SARS-CoV-2 infection in mice and enable long-term protective immunity
Authors: Mougari Said , Favède Valérie , Predella Camilla , Reynard Olivier , Durand Stephanie , Mazelier Magalie , Pizzioli Edoardo , Decimo Didier , Bovier Francesca T. , Lapsley Lauren M. , Castagna Candace , Lieberman Nicole A. P. , Noel Guillaume , Mathieu Cyrille , Malissen Bernard , Briese Thomas , Greninger Alexander L. , Alabi Christopher A. , Dorrello N. Valerio , Marot Stéphane , Marcelin Anne-Geneviève , Zarubica Ana , Moscona Anne , Porotto Matteo , Horvat Branka
Published: January 2025

We have assessed antiviral activity and induction of protective immunity of fusion-inhibitory lipopeptides derived from the C-terminal heptad-repeat domain of SARS-CoV-2 spike glycoprotein in transgenic mice expressing human ACE2 (K18-hACE2). The lipopeptides block SARS-CoV-2 infection in cell lines and lung-derived organotypic cultures. Intranasal administration in mice allows the maintenance of homeostatic transcriptomic immune profile in lungs, prevents body-weight loss, decreases viral load and shedding, and protects mice from death caused by SARS-CoV-2 variants. Prolonged administration of high-dose lipopeptides has neither adverse effects nor impairs peptide efficacy in subsequent SARS-CoV-2 challenges. The peptide-protected mice develop cross-reactive neutralizing antibodies against both SARS-CoV-2 used for the initial infection and recently circulating variants, and are completely protected from a second lethal infection, suggesting that they developed SARS-CoV-2-specific immunity. This strategy provides an additional antiviral approach in the global effort against COVID-19 and may contribute to development of rapid responses against emerging pathogenic viruses.
Unified study of viscoelasticity and sound damping in hard and soft amorphous solids
Authors: Mizuno Hideyuki , Saitoh Kuniyasu , Hara Yusuke , Ikeda Atsushi
Published: January 2025

Amorphous solids are diverse materials that take on various forms such as structural glasses, granular materials, foams, emulsions, and biological systems. Recent research has made significant progress in understanding non-phonon vibrational modes universally present in amorphous materials, which have been observed as excess vibrational modes over the Debye law, known as boson peak, as well as quasi-localized vibrational modes. These vibrational modes are crucial to explaining material properties of a wide range of amorphous materials, from “hard" solids like structural glasses to “soft" solids like foams and emulsions. However, we still lack a theoretical framework that can comprehensively explain them in a unified manner. Here, we propose a unified theory for viscoelasticity and sound damping which are significantly different between hard and soft amorphous solids but are ultimately determined by non-Debye scaling laws of the non-phonon vibrational modes. Our theory can explain acoustic properties of structural glasses, which have been measured experimentally with light, inelastic X-ray, and neutron scattering techniques, on one hand, and viscoelastic properties of foams and emulsions, which have been measured by various macrorheology and microrheology techniques, on the other. We thus provide a comprehensive explanation for these experimental measurements of two distinct types of amorphous solids.
Depression symptom-specific genetic associations in clinically diagnosed and proxy case Alzheimer’s disease
Authors: Gilchrist Lachlan , Spargo Thomas P. , Green Rebecca E. , Coleman Jonathan R. I. , Howard David M. , Thorp Jackson G. , Adey Brett N. , Lord Jodie , Davies Helena L. , Mundy Jessica , ter Kuile Abigail R. , Davies Molly R. , Hübel Christopher , Bristow Shannon , Lee Sang Hyuck , Rogers Henry , Curtis Charles , Kakar Saakshi , Malouf Chelsea M. , Kalsi Gursharan , Arathimos Ryan , Corbett Anne , Ballard Clive , Brooker Helen , Creese Byron , Aarsland Dag , Hampshire Adam , Velayudhan Latha , Eley Thalia C. , Breen Gerome , Iacoangeli Alfredo , Kõks Sulev , Lewis Cathryn M. , Proitsi Petroula
Published: January 2025

Depression is a risk factor for the later development of Alzheimer’s disease (AD), but evidence for the genetic relationship is mixed. Assessing depression symptom-specific genetic associations may better clarify this relationship. To address this, we conducted genome-wide meta-analysis (a genome-wide association study, GWAS) of the nine depression symptom items, plus their sum score, on the Patient Health Questionnaire (PHQ-9) (GWAS-equivalent N: 224,535–308,421) using data from UK Biobank, the GLAD study and PROTECT, identifying 37 genomic risk loci. Using six AD GWASs with varying proportions of clinical and proxy (family history) case ascertainment, we identified 20 significant genetic correlations with depression/depression symptoms. However, only one of these was identified with a clinical AD GWAS. Local genetic correlations were detected in 14 regions. No statistical colocalization was identified in these regions. However, the region of the transmembrane protein 106B gene (TMEM106B) showed colocalization between multiple depression phenotypes and both clinical-only and clinical + proxy AD. Mendelian randomization and polygenic risk score analyses did not yield significant results after multiple testing correction in either direction. Our findings do not demonstrate a causal role of depression/depression symptoms on AD and suggest that previous evidence of genetic overlap between depression and AD may be driven by the inclusion of family history-based proxy cases/controls. However, colocalization at TMEM106B warrants further investigation.
3D-printed devices for multiplexed semi-quantitative competitive lateral flow immunoassays
Authors: Tong Guodong , Misawa Kazushi , Jarujamrus Purim , Hiruta Yuki , Citterio Daniel
Published: January 2025

A 3D-printed device enabling multiplex lateral flow immunoassays and semi-quantitative result readout with less sample volume.
Heterogeneous copper-catalyzed Grignard reactions with allylic substrates
Authors: Mondal Shobhan , Deiana Luca , Córdova Armando , Wu Haibo , Bäckvall Jan-E.
Published: January 2025

Herein, we report the first example of heterogeneous catalysis for the cross-coupling of allylic alcohol substrates with Grignard reagents. The method features high yields, excellent regioselectivity, and complete chirality transfer.
Enhanced charge transfer kinetics at the electrode/electrolyte interface in acetonitrile solvent for lithium-ion battery cathodes
Authors: Suzuki Tatsumi , Miyaura Yuki , Okazaki Ken-ichi , Zhong Chengchao , Shimoda Keiji , Kondo Fumiya , Fujii Masanori , Kinoshita Hajime , Orikasa Yuki
Published: January 2025

Acetonitrile improves the rate capability of Li-ion batteries by enhancing the charge transfer kinetics at the electrode/electrolyte interface.
FEMC-deuterogenic artificial solid electrolyte interphase boosts high-performance sodium-ion batteries
Authors: Miao Sicheng , Jia Ye , Chen Ruoxuan , Pan Yueqi , Peng Jianan , Zhang Xuemei , Cai Wenlong
Published: January 2025

This work constructs an artificial interphase by a simple chemical reaction that can induce uniform deposition of sodium, thus achieving high-performance sodium metal batteries.
Synthesis of chiral N-free sulfinamides by asymmetric condensation of stable sulfinates and ammonium salts
Authors: Xiong Qin , Liao Minghong , Wang Gangyu , Shi Hai , Wu Xingxing
Published: January 2025

An organocatalytic approach using stable, cost-effective ammonium salts for asymmetric sulfinylation, achieving a broad range of enantioenriched sulfinamides was disclosed.
Advances in accessing rare oxidation states of nickel for catalytic innovation
Authors: Khamrai Aankhi , Ghosh Sudipta , Ganesh Venkataraman
Published: January 2025

Nickel catalysis has experienced a renaissance over the past two decades, driven by its ability to access diverse oxidation states (0 to +4). This review consolidates the advancements in nickel chemistry at its various oxidation states.
Recent innovations in in situ strategies to prepare metal–organic framework-based mixed matrix membranes
Authors: Zhang Liying , He Yuxin , Fu Yu
Published: January 2025

In situ strategies to construct MOF-based MMMs are reviewed in the present study.
Dimerizing DNA-AgNCs via a C–Ag+–C structure for fluorescence sensing with dual-output signals
Authors: Chen Shuai , Hu Wenjie , Cheng Yuqi , Yin Zhiwei , Xiao Jiaxiang , Li Changwen , Zhao Haihong , Dong Qian , Chen Zhuo
Published: January 2025

The unique insertion capability of Ag+ into cytosine–cytosine (C–Ag+–C) mismatch-base pairs enables precise fabrication of DNA-trapped silver nanoclusters (DNA-AgNCs) for enormous fluorescence applications.
Crystal/magnetic structure and cation inversion in hydrothermally synthesized MnFe2O4, CoFe2O4, NiFe2O4, and ZnFe2O4 nanoparticles: a neutron powder diffraction study
Authors: Andersen Henrik L. , Saura-Múzquiz Matilde , Granados-Miralles Cecilia , Klemmt Rebekka , Bøjesen Espen D. , Christensen Mogens
Published: January 2025

Joint PXRD and NPD analysis of crystal and magnetic structures of MnFe2O4, CoFe2O4, NiFe2O4 and ZnFe2O4 nanoparticles reveal how cation type affects spinel inversion, crystallite size, and magnetism.
Knowledge-driven design of boron-based catalysts for oxidative dehydrogenation of propane
Authors: Chen Weixi , Liu Ziyi , Zhu Lihan , Wang Dongqi
Published: January 2025

Knowledge on ODH established via computational and experimental studies drives rational design of novel catalysts and optimization of catalytic systems, which can also embrace machine learning in the future, benefiting from historic data.
Selective sensing of NH3 and NO2 on WSe2 monolayers based on defect concentration regulation
Authors: Zhang Jinghao , Zhang Yunfan , Tian FengHui , Sun Luxiao , Zhang Xiaodong , Fu Aiping , Tian Mingwei
Published: January 2025

Respective selective sensing of NH3 and NO2 on WSe2 monolayers with different Se vacancy concentrations.