bluuebunny/crossref_metadata_2025_split huggingface dataset:
Understanding quantum machine learning also requires rethinking generalization
Authors: Gil-Fuster Elies , Eisert Jens , Bravo-Prieto Carlos 
Published: March 2024

AbstractQuantum machine learning models have shown successful generalization performance even when trained with few data. In this work, through systematic randomization experiments, we show that traditional approaches to understanding generalization fail to explain the behavior of such quantum models. Our experiments reveal that state-of-the-art quantum neural networks accurately fit random states and random labeling of training data. This ability to memorize random data defies current notions of small generalization error, problematizing approaches that build on complexity measures such as the VC dimension, the Rademacher complexity, and all their uniform relatives. We complement our empirical results with a theoretical construction showing that quantum neural networks can fit arbitrary labels to quantum states, hinting at their memorization ability. Our results do not preclude the possibility of good generalization with few training data but rather rule out any possible guarantees based only on the properties of the model family. These findings expose a fundamental challenge in the conventional understanding of generalization in quantum machine learning and highlight the need for a paradigm shift in the study of quantum models for machine learning tasks.
Charting cellular differentiation trajectories with Ricci flow
Authors: Baptista Anthony , MacArthur Ben D. , Banerji Christopher R. S. 
Published: March 2024

AbstractComplex biological processes, such as cellular differentiation, require intricate rewiring of intra-cellular signalling networks. Previous characterisations revealed a raised network entropy underlies less differentiated and malignant cell states. A connection between entropy and Ricci curvature led to applications of discrete curvatures to biological networks. However, predicting dynamic biological network rewiring remains an open problem. Here we apply Ricci curvature and Ricci flow to biological network rewiring. By investigating the relationship between network entropy and Forman-Ricci curvature, theoretically and empirically on single-cell RNA-sequencing data, we demonstrate that the two measures do not always positively correlate, as previously suggested, and provide complementary rather than interchangeable information. We next employ Ricci flow to derive network rewiring trajectories from stem cells to differentiated cells, accurately predicting true intermediate time points in gene expression time courses. In summary, we present a differential geometry toolkit for understanding dynamic network rewiring during cellular differentiation and cancer.
Population exposure to multiple air pollutants and its compound episodes in Europe
Authors: Chen Zhao-Yue , Petetin Hervé , Méndez Turrubiates Raúl Fernando , Achebak Hicham , Pérez García-Pando Carlos , Ballester Joan 
Published: March 2024

AbstractAir pollution remains as a substantial health problem, particularly regarding the combined health risks arising from simultaneous exposure to multiple air pollutants. However, understanding these combined exposure events over long periods has been hindered by sparse and temporally inconsistent monitoring data. Here we analyze daily ambient PM2.5, PM10, NO2 and O3 concentrations at a 0.1-degree resolution during 2003–2019 across 1426 contiguous regions in 35 European countries, representing 543 million people. We find that PM10 levels decline by 2.72% annually, followed by NO2 (2.45%) and PM2.5 (1.72%). In contrast, O3 increase by 0.58% in southern Europe, leading to a surge in unclean air days. Despite air quality advances, 86.3% of Europeans experience at least one compound event day per year, especially for PM2.5-NO2 and PM2.5-O3. We highlight the improvements in air quality control but emphasize the need for targeted measures addressing specific pollutants and their compound events, particularly amidst rising temperatures.
Enantioselective functionalization of unactivated C(sp3)–H bonds through copper-catalyzed diyne cyclization by kinetic resolution
Authors: Chen Yang-Bo , Liu Li-Gao , Wang Zhe-Qi , Chang Rong , Lu Xin , Zhou Bo , Ye Long-Wu 
Published: March 2024

AbstractSite- and stereoselective C–H functionalization is highly challenging in the synthetic chemistry community. Although the chemistry of vinyl cations has been vigorously studied in C(sp3)–H functionalization reactions, the catalytic enantioselective C(sp3)–H functionalization based on vinyl cations, especially for an unactivated C(sp3)–H bond, has scarcely explored. Here, we report an asymmetric copper-catalyzed tandem diyne cyclization/unactivated C(sp3)–H insertion reaction via a kinetic resolution, affording both chiral polycyclic pyrroles and diynes with generally excellent enantioselectivities and excellent selectivity factors (up to 750). Importantly, this reaction demonstrates a metal-catalyzed enantioselective unactivated C(sp3)–H functionalization via vinyl cation and constitutes a kinetic resolution reaction based on diyne cyclization. Theoretical calculations further support the mechanism of vinyl cation-involved C(sp3)–H insertion reaction and elucidate the origin of enantioselectivity.
Divergent dynamics of sexual and habitat isolation at the transition between stick insect populations and species
Authors: Nosil Patrik , Gompert Zachariah , Funk Daniel J. 
Published: March 2024

AbstractSpeciation is often viewed as a continuum along which populations diverge until they become reproductively-isolated species. However, such divergence may be heterogeneous, proceeding in fits and bursts, rather than being uniform and gradual. We show in Timema stick insects that one component of reproductive isolation evolves non-uniformly across this continuum, whereas another does not. Specifically, we use thousands of host-preference and mating trials to study habitat and sexual isolation among 42 pairs of taxa spanning a range of genomic differentiation and divergence time. We find that habitat isolation is uncoupled from genomic differentiation within species, but accumulates linearly with it between species. In contrast, sexual isolation accumulates linearly across the speciation continuum, and thus exhibits similar dynamics to morphological traits not implicated in reproductive isolation. The results show different evolutionary dynamics for different components of reproductive isolation and highlight a special relevance for species status in the process of speciation.
NME3 is a gatekeeper for DRP1-dependent mitophagy in hypoxia
Authors: Chen Chih-Wei , Su Chi , Huang Chang-Yu , Huang Xuan-Rong , Cuili Xiaojing , Chao Tung , Fan Chun-Hsiang , Ting Cheng-Wei , Tsai Yi-Wei , Yang Kai-Chien , Yeh Ti-Yen , Hsieh Sung-Tsang , Chen Yi-Ju , Feng Yuxi , Hunter Tony , Chang Zee-Fen 
Published: March 2024

AbstractNME3 is a member of the nucleoside diphosphate kinase (NDPK) family localized on the mitochondrial outer membrane (MOM). Here, we report a role of NME3 in hypoxia-induced mitophagy dependent on its active site phosphohistidine but not the NDPK function. Mice carrying a knock-in mutation in the Nme3 gene disrupting NME3 active site histidine phosphorylation are vulnerable to ischemia/reperfusion-induced infarction and develop abnormalities in cerebellar function. Our mechanistic analysis reveals that hypoxia-induced phosphatidic acid (PA) on mitochondria is essential for mitophagy and the interaction of DRP1 with NME3. The PA binding function of MOM-localized NME3 is required for hypoxia-induced mitophagy. Further investigation demonstrates that the interaction with active NME3 prevents DRP1 susceptibility to MUL1-mediated ubiquitination, thereby allowing a sufficient amount of active DRP1 to mediate mitophagy. Furthermore, MUL1 overexpression suppresses hypoxia-induced mitophagy, which is reversed by co-expression of ubiquitin-resistant DRP1 mutant or histidine phosphorylatable NME3. Thus, the site-specific interaction with active NME3 provides DRP1 a microenvironment for stabilization to proceed the segregation process in mitophagy.
Electrostatic potentials of atomic nanostructures at metal surfaces quantified by scanning quantum dot microscopy
Authors: Bolat Rustem , Guevara Jose M. , Leinen Philipp , Knol Marvin , Arefi Hadi H. , Maiworm Michael , Findeisen Rolf , Temirov Ruslan , Hofmann Oliver T. , Maurer Reinhard J. , Tautz F. Stefan , Wagner Christian 
Published: March 2024

AbstractThe discrete and charge-separated nature of matter — electrons and nuclei — results in local electrostatic fields that are ubiquitous in nanoscale structures and relevant in catalysis, nanoelectronics and quantum nanoscience. Surface-averaging techniques provide only limited experimental access to these potentials, which are determined by the shape, material, and environment of the nanostructure. Here, we image the potential over adatoms, chains, and clusters of Ag and Au atoms assembled on Ag(111) and quantify their surface dipole moments. By focusing on the total charge density, these data establish a benchmark for theory. Our density functional theory calculations show a very good agreement with experiment and allow a deeper analysis of the dipole formation mechanisms, their dependence on fundamental atomic properties and on the shape of the nanostructures. We formulate an intuitive picture of the basic mechanisms behind dipole formation, allowing better design choices for future nanoscale systems such as single-atom catalysts.
Nanobubble-actuated ultrasound neuromodulation for selectively shaping behavior in mice
Authors: Hou Xuandi , Jing Jianing , Jiang Yizhou , Huang Xiaohui , Xian Quanxiang , Lei Ting , Zhu Jiejun , Wong Kin Fung , Zhao Xinyi , Su Min , Li Danni , Liu Langzhou , Qiu Zhihai , Sun Lei 
Published: March 2024

AbstractUltrasound is an acoustic wave which can noninvasively penetrate the skull to deep brain regions, enabling neuromodulation. However, conventional ultrasound’s spatial resolution is diffraction-limited and low-precision. Here, we report acoustic nanobubble-mediated ultrasound stimulation capable of localizing ultrasound’s effects to only the desired brain region in male mice. By varying the delivery site of nanobubbles, ultrasound could activate specific regions of the mouse motor cortex, evoking EMG signaling and limb movement, and could also, separately, activate one of two nearby deep brain regions to elicit distinct behaviors (freezing or rotation). Sonicated neurons displayed reversible, low-latency calcium responses and increased c-Fos expression in the sub-millimeter-scale region with nanobubbles present. Ultrasound stimulation of the relevant region also modified depression-like behavior in a mouse model. We also provide evidence of a role for mechanosensitive ion channels. Altogether, our treatment scheme allows spatially-targetable, repeatable and temporally-precise activation of deep brain circuits for neuromodulation without needing genetic modification.
Single-cell division tracing and transcriptomics reveal cell types and differentiation paths in the regenerating lung
Authors: Martins Leila R. , Sieverling Lina , Michelhans Michelle , Schiller Chiara , Erkut Cihan , Grünewald Thomas G. P. , Triana Sergio , Fröhling Stefan , Velten Lars , Glimm Hanno , Scholl Claudia 
Published: March 2024

AbstractUnderstanding the molecular and cellular processes involved in lung epithelial regeneration may fuel the development of therapeutic approaches for lung diseases. We combine mouse models allowing diphtheria toxin-mediated damage of specific epithelial cell types and parallel GFP-labeling of functionally dividing cells with single-cell transcriptomics to characterize the regeneration of the distal lung. We uncover cell types, including Krt13+ basal and Krt15+ club cells, detect an intermediate cell state between basal and goblet cells, reveal goblet cells as actively dividing progenitor cells, and provide evidence that adventitial fibroblasts act as supporting cells in epithelial regeneration. We also show that diphtheria toxin-expressing cells can persist in the lung, express specific inflammatory factors, and transcriptionally resemble a previously undescribed population in the lungs of COVID-19 patients. Our study provides a comprehensive single-cell atlas of the distal lung that characterizes early transcriptional and cellular responses to concise epithelial injury, encompassing proliferation, differentiation, and cell-to-cell interactions.
PRMT5 is an actionable therapeutic target in CDK4/6 inhibitor-resistant ER+/RB-deficient breast cancer
Authors: Lin Chang-Ching , Chang Tsung-Cheng , Wang Yunguan , Guo Lei , Gao Yunpeng , Bikorimana Emmanuel , Lemoff Andrew , Fang Yisheng V. , Zhang He , Zhang Yanfeng , Ye Dan , Soria-Bretones Isabel , Servetto Alberto , Lee Kyung-min , Luo Xuemei , Otto Joseph J. , Akamatsu Hiroaki , Napolitano Fabiana , Mani Ram , Cescon David W. , Xu Lin , Xie Yang , Mendell Joshua T. , Hanker Ariella B. , Arteaga Carlos L. 
Published: March 2024

AbstractCDK4/6 inhibitors (CDK4/6i) have improved survival of patients with estrogen receptor-positive (ER+) breast cancer. However, patients treated with CDK4/6i eventually develop drug resistance and progress. RB1 loss-of-function alterations confer resistance to CDK4/6i, but the optimal therapy for these patients is unclear. Through a genome-wide CRISPR screen, we identify protein arginine methyltransferase 5 (PRMT5) as a molecular vulnerability in ER+/RB1-knockout breast cancer cells. Inhibition of PRMT5 blocks the G1-to-S transition in the cell cycle independent of RB, leading to growth arrest in RB1-knockout cells. Proteomics analysis uncovers fused in sarcoma (FUS) as a downstream effector of PRMT5. Inhibition of PRMT5 results in dissociation of FUS from RNA polymerase II, leading to hyperphosphorylation of serine 2 in RNA polymerase II, intron retention, and subsequent downregulation of proteins involved in DNA synthesis. Furthermore, treatment with the PRMT5 inhibitor pemrametostat and a selective ER degrader fulvestrant synergistically inhibits growth of ER+/RB-deficient cell-derived and patient-derived xenografts. These findings highlight dual ER and PRMT5 blockade as a potential therapeutic strategy to overcome resistance to CDK4/6i in ER+/RB-deficient breast cancer.
Interfacial ice sprouting during salty water droplet freezing
Authors: Chu Fuqiang , Li Shuxin , Zhao Canjun , Feng Yanhui , Lin Yukai , Wu Xiaomin , Yan Xiao , Miljkovic Nenad 
Published: March 2024

AbstractIcing of seawater droplets is capable of causing catastrophic damage to vessels, buildings, and human life, yet it also holds great potential for enhancing applications such as droplet-based freeze desalination and anti-icing of sea sprays. While large-scale sea ice growth has been investigated for decades, the icing features of small salty droplets remain poorly understood. Here, we demonstrate that salty droplet icing is governed by salt rejection-accompanied ice crystal growth, resulting in freezing dynamics different from pure water. Aided by the observation of brine films emerging on top of frozen salty droplets, we propose a universal definition of freezing duration to quantify the icing rate of droplets having varying salt concentrations. Furthermore, we show that the morphology of frozen salty droplets is governed by ice crystals that sprout from the bottom of the brine film. These crystals grow until they pierce the free interface, which we term ice sprouting. We reveal that ice sprouting is controlled by condensation at the brine film free interface, a mechanism validated through molecular dynamics simulations. Our findings shed light on the distinct physics that govern salty droplet icing, knowledge that is essential for the development of related technologies.
Broadband angular spectrum differentiation using dielectric metasurfaces
Authors: Deng Ming , Cotrufo Michele , Wang Jian , Dong Jianji , Ruan Zhichao , Alù Andrea , Chen Lin 
Published: March 2024

AbstractSignal processing is of critical importance for various science and technology fields. Analog optical processing can provide an effective solution to perform large-scale and real-time data processing, superior to its digital counterparts, which have the disadvantages of low operation speed and large energy consumption. As an important branch of modern optics, Fourier optics exhibits great potential for analog optical image processing, for instance for edge detection. While these operations have been commonly explored to manipulate the spatial content of an image, mathematical operations that act directly over the angular spectrum of an image have not been pursued. Here, we demonstrate manipulation of the angular spectrum of an image, and in particular its differentiation, using dielectric metasurfaces operating across the whole visible spectrum. We experimentally show that this technique can be used to enhance desired portions of the angular spectrum of an image. Our approach can be extended to develop more general angular spectrum analog meta-processors, and may open opportunities for optical analog data processing and biological imaging.
Cost-effectiveness uncertainty may bias the decision of coal power transitions in China
Authors: Yan Xizhe , Tong Dan , Zheng Yixuan , Liu Yang , Chen Shaoqing , Qin Xinying , Chen Chuchu , Xu Ruochong , Cheng Jing , Shi Qinren , Zheng Dongsheng , He Kebin , Zhang Qiang , Lei Yu 
Published: March 2024

AbstractA transition away from coal power always maintains a high level of complexity as there are several overlapping considerations such as technical feasibility, economic costs, and environmental and health impacts. Here, we explore the cost-effectiveness uncertainty brought by policy implementation disturbances of different coal power phaseout and new-built strategies (i.e., the disruption of phaseout priority) in China based on a developed unit-level uncertainty assessment framework. We reveal the opportunity and risk of coal transition decisions by employing preference analysis. We find that, the uncertainty of a policy implementation might lead to potential delays in yielding the initial positive annual net benefits. For example, a delay of six years might occur when implementing the prior phaseout practice. A certain level of risk remains in the implementation of the phaseout policy, as not all strategies can guarantee the cumulative positive net benefits from 2018–2060. Since the unit-level heterogeneities shape diverse orientation of the phaseout, the decision-making preferences would remarkably alter the selection of a coal power transition strategy. More strikingly, the cost-effectiveness uncertainty might lead to missed opportunities in identifying an optimal strategy. Our results highlight the importance of minimizing the policy implementation disturbance, which helps mitigate the risk of negative benefits and strengthen the practicality of phaseout decisions.
Bacteriophage DNA induces an interrupted immune response during phage therapy in a chicken model
Authors: Podlacha Magdalena , Gaffke Lidia , Grabowski Łukasz , Mantej Jagoda , Grabski Michał , Pierzchalska Małgorzata , Pierzynowska Karolina , Węgrzyn Grzegorz , Węgrzyn Alicja 
Published: March 2024

AbstractOne of the hopes for overcoming the antibiotic resistance crisis is the use of bacteriophages to combat bacterial infections, the so-called phage therapy. This therapeutic approach is generally believed to be safe for humans and animals as phages should infect only prokaryotic cells. Nevertheless, recent studies suggested that bacteriophages might be recognized by eukaryotic cells, inducing specific cellular responses. Here we show that in chickens infected with Salmonella enterica and treated with a phage cocktail, bacteriophages are initially recognized by animal cells as viruses, however, the cGAS-STING pathway (one of two major pathways of the innate antiviral response) is blocked at the stage of the IRF3 transcription factor phosphorylation. This inhibition is due to the inability of RNA polymerase III to recognize phage DNA and to produce dsRNA molecules which are necessary to stimulate a large protein complex indispensable for IRF3 phosphorylation, indicating the mechanism of the antiviral response impairment.
Natural variation in OsMYB8 confers diurnal floret opening time divergence between indica and japonica subspecies
Authors: Gou Yajun , Heng Yueqin , Ding Wenyan , Xu Canhong , Tan Qiushuang , Li Yajing , Fang Yudong , Li Xiaoqing , Zhou Degui , Zhu Xinyu , Zhang Mingyue , Ye Rongjian , Wang Haiyang , Shen Rongxin 
Published: March 2024

AbstractThe inter-subspecific indica-japonica hybrid rice confer potential higher yield than the widely used indica-indica intra-subspecific hybrid rice. Nevertheless, the utilization of this strong heterosis is currently hindered by asynchronous diurnal floret opening time (DFOT) of indica and japonica parental lines. Here, we identify OsMYB8 as a key regulator of rice DFOT. OsMYB8 induces the transcription of JA-Ile synthetase OsJAR1, thereby regulating the expression of genes related to cell osmolality and cell wall remodeling in lodicules to promote floret opening. Natural variations of OsMYB8 promoter contribute to its differential expression, thus differential transcription of OsJAR1 and accumulation of JA-Ile in lodicules of indica and japonica subspecies. Furthermore, introgression of the indica haplotype of OsMYB8 into japonica effectively promotes DFOT in japonica. Our findings reveal an OsMYB8-OsJAR1 module that regulates differential DFOT in indica and japonica, and provide a strategy for breeding early DFOT japonica to facilitate breeding of indica-japonica hybrids.
The decline of the 2022 Italian mpox epidemic: Role of behavior changes and control strategies
Authors: Guzzetta Giorgio , Marziano Valentina , Mammone Alessia , Siddu Andrea , Ferraro Federica , Caraglia Anna , Maraglino Francesco , Rezza Giovanni , Vespignani Alessandro , Longini Ira , Ajelli Marco , Merler Stefano 
Published: March 2024

AbstractIn 2022, a global outbreak of mpox occurred, predominantly impacting men who have sex with men (MSM). The rapid decline of this epidemic is yet to be fully understood. We investigated the Italian outbreak by means of an individual-based mathematical model calibrated to surveillance data. The model accounts for transmission within the MSM sexual contact network, in recreational and sex clubs attended by MSM, and in households. We indicate a strong spontaneous reduction in sexual transmission (61-87%) in affected MSM communities as the possible driving factor for the rapid decline in cases. The MSM sexual contact network was the main responsible for transmission (about 80%), with clubs and households contributing residually. Contact tracing prevented about half of the potential cases, and a higher success rate in tracing contacts could significantly amplify its effectiveness. Notably, immunizing the 23% of MSM with the highest sexual activity (10 or more partners per year) could completely prevent new mpox resurgences. This research underscores the importance of augmenting contact tracing, targeted immunization campaigns of high-risk groups, and fostering reactive behavioral changes as key strategies to manage and prevent the spread of emerging sexually transmitted pathogens like mpox within the MSM community.