PNAS nexus最新文献_第2页

Detecting and forecasting tipping points from sample variance alone. 仅从样本方差检测和预测引爆点。

IF 3.8

PNAS nexus Pub Date : 2026-04-16 eCollection Date: 2026-04-01 DOI: 10.1093/pnasnexus/pgag126

Naoki Masuda

{"title":"Detecting and forecasting tipping points from sample variance alone.","authors":"Naoki Masuda","doi":"10.1093/pnasnexus/pgag126","DOIUrl":"https://doi.org/10.1093/pnasnexus/pgag126","url":null,"abstract":"Anticipating tipping points in complex systems is a fundamental challenge across domains. Traditional early warning signals (EWSs) based on critical slowing down, such as increasing sample variance, are widely used, but their ability to reliably indicate imminent bifurcations and forecast their timing remains limited. Here, we introduce TIPMOC (TIpping via Power-law fits and MOdel Comparison), a parametric framework designed to statistically detect the approach of a bifurcation and estimate its future location using only the sample variance. TIPMOC exploits the mathematical property that variance diverges with a characteristic power-law form near codimension-one bifurcations. By sequentially monitoring system variance as a control parameter changes, TIPMOC statistically adjudicates between linear and power-law divergence at each step. When evidence favors power-law divergence, TIPMOC forecasts the impending tipping point and estimates its position; otherwise, it avoids false positives. Through numerical simulations, we demonstrate TIPMOC's robustness and accuracy in both detection and timing prediction across different types of dynamics and bifurcation, whereas the accuracy of timing prediction is limited. TIPMOC shows low false positive rates and performs well even with uneven sampling and colored noise. This method thus enhances the interpretability and practical utility of classical EWSs, serving as both a transparent add-on and a stand-alone statistical tool for forecasting regime shifts in diverse complex systems.","PeriodicalId":74468,"journal":{"name":"PNAS nexus","volume":"5 4","pages":"pgag126"},"PeriodicalIF":3.8,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13123519/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147791730","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Aging disrupts the temporal organization of slow oscillations beyond density reduction. 老化破坏了密度降低之外的缓慢振荡的时间组织。

IF 3.8

PNAS nexus Pub Date : 2026-04-16 eCollection Date: 2026-04-01 DOI: 10.1093/pnasnexus/pgag108

Lucila Capurro, Michael Radloff, María C González, María L Gorosito, Luis I Brusco, Rodrigo Ramele, Cecilia Forcato

{"title":"Aging disrupts the temporal organization of slow oscillations beyond density reduction.","authors":"Lucila Capurro, Michael Radloff, María C González, María L Gorosito, Luis I Brusco, Rodrigo Ramele, Cecilia Forcato","doi":"10.1093/pnasnexus/pgag108","DOIUrl":"10.1093/pnasnexus/pgag108","url":null,"abstract":"Macroscopic and rhythmic brain oscillations have recently been shown to play a crucial role in glymphatic function by promoting cerebrospinal fluid flow and facilitating the clearance of metabolic waste. While age-related reductions in the number and amplitude of slow oscillations (SOs; 0.5-1 Hz) are well documented and associated with impaired clearance, little is known about how aging affects the temporal structure of these oscillations. Here, we propose that the rhythmic dynamics with which SOs occur represent a critical, yet overlooked, feature supporting glymphatic function. We introduce a novel classification of SOs based on their temporal organization, distinguishing isolated SOs from trains of consecutive oscillations according to inter-SO intervals. Using overnight electroencephalographic recordings from 57 young and 51 elderly adults across three independent datasets, we compared the proportions of isolated and consecutive SOs as well as the distribution of train lengths. Elderly adults displayed a significantly higher proportion of isolated SOs and shorter oscillatory trains than young adults, even after controlling for SO density and stage composition. Temporal shuffling procedures and analyses of density-matched epochs further supported that these differences cannot be attributed solely to density but instead reflect a genuine age-related loss of rhythmicity. These findings reveal that natural aging not only reduces the amount and amplitude of SOs but also disrupts their temporal regularity. This alteration may weaken the sustained ionic currents that drive cerebrospinal fluid flow, compromise the efficiency of metabolic clearance during sleep, and thereby contribute to increased vulnerability to age-related neurodegenerative processes.","PeriodicalId":74468,"journal":{"name":"PNAS nexus","volume":"5 4","pages":"pgag108"},"PeriodicalIF":3.8,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13091574/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147724981","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Entropy production bounds for systems running computer programs. 运行计算机程序的系统的熵产界。

IF 3.8

PNAS nexus Pub Date : 2026-04-16 eCollection Date: 2026-04-01 DOI: 10.1093/pnasnexus/pgag116

Abhishek Yadav, Francesco Caravelli, David Wolpert

引用次数: 0

Turbulence-induced fluctuating interfaces in heterogeneously active suspensions. 非均质主动悬架中湍流诱导的波动界面。

IF 3.8

PNAS nexus Pub Date : 2026-04-16 eCollection Date: 2026-05-01 DOI: 10.1093/pnasnexus/pgag125

Siddhartha Mukherjee, Kunal Kumar, Samriddhi Sankar Ray

引用次数: 0

Comparative transcriptomics reveals differences in cortical cell type organization between metatherian and eutherian mammals. 比较转录组学揭示了后兽和真兽之间皮层细胞类型组织的差异。

IF 3.8

PNAS nexus Pub Date : 2026-04-16 eCollection Date: 2026-04-01 DOI: 10.1093/pnasnexus/pgag055

Ryan Gorzek, Joshua T Trachtenberg

{"title":"Comparative transcriptomics reveals differences in cortical cell type organization between metatherian and eutherian mammals.","authors":"Ryan Gorzek, Joshua T Trachtenberg","doi":"10.1093/pnasnexus/pgag055","DOIUrl":"10.1093/pnasnexus/pgag055","url":null,"abstract":"The neocortex, a layered structure unique to mammals, supports higher-order functions, including perception, learning, and decision-making. While its laminar architecture is broadly conserved, the cell type-specific organization of the cortical column has not been compared across species that diverged early in mammalian evolution. To address this, we used single-nucleus RNA sequencing and spatial transcriptomics to compare gene expression, cell types, and laminar architecture in the primary visual cortex (V1) of metatherian (Monodelphis domestica) and eutherian (Mus musculus) mammals. We show that spatio-transcriptomic distinctions between supragranular (layer 2/3) and infragranular (layer 5) intratelencephalic neurons are more pronounced in mice, consistent with lineage-specific specialization. Mouse cortex also exhibits a lower relative density of parvalbumin-positive GABAergic neurons and redistributed perineuronal nets, consistent with altered constraints on plasticity. Together, these findings demonstrate substantial variation in the cellular and spatial organization of the cortical column across deeply diverged mammals, challenging the view that local cortical architecture is uniformly conserved.","PeriodicalId":74468,"journal":{"name":"PNAS nexus","volume":"5 4","pages":"pgag055"},"PeriodicalIF":3.8,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13089494/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147725019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Supply chain network rewiring dynamics at the firm level. 企业层面的供应链网络重构动力学。

IF 3.8

PNAS nexus Pub Date : 2026-04-16 eCollection Date: 2026-04-01 DOI: 10.1093/pnasnexus/pgag091

Tobias Reisch, András Borsos, Stefan Thurner

{"title":"Supply chain network rewiring dynamics at the firm level.","authors":"Tobias Reisch, András Borsos, Stefan Thurner","doi":"10.1093/pnasnexus/pgag091","DOIUrl":"https://doi.org/10.1093/pnasnexus/pgag091","url":null,"abstract":"Supply chain networks (SCN) form the structural backbone of any society. They constitute the societal metabolism that literally produces everything for everybody by coordinating practically every single person on the planet. SCNs are by no means static but undergo permanent change through the entry and exit of firms and the rearrangement of supply relations. Here, we use a unique dataset to explore the temporal evolution of firms and their supplier-buyer relations of a national SCN. Monthly reported value added tax data from Hungary from 2014 to 2022 allows us to reconstruct the entire economy with 711,248 companies and 38,644,400 connections, covering practically every restructuring event of an entire economy at firm-level resolution. We find that per year about 25% of firms exit the SCN while 28% new ones enter. On average, 55% of all supply-links present in 1 year will not be present in the next. We report the half-life time of supply-links to be 13 months. New links attach super-preferentially to firms with a probability, <math><mi>p</mi> <mo>(</mo> <mi>i</mi> <mo>)</mo> <mo>∝</mo> <msubsup><mi>k</mi> <mi>i</mi> <mrow><mn>1.08</mn></mrow> </msubsup> </math> , with <math><msub><mi>k</mi> <mi>i</mi></msub> </math> firm i's number of supply connections. We calibrate a simple statistical network generation model that reproduces the stylized characteristics of the dominant Hungarian SCN. The model not only reproduces local network features such as in- and out-degree distributions, assortativity, and clustering structure but also captures realistic systemic risk profiles. We discuss the present model in how rewiring dynamics of the economy is essential for quantifying its resilience and to estimate shock propagation.","PeriodicalId":74468,"journal":{"name":"PNAS nexus","volume":"5 4","pages":"pgag091"},"PeriodicalIF":3.8,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13126663/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147824459","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Humans can rebuild severely eroded resilience: Demo with millennia-long records in China's Loess Plateau. 人类可以重建严重侵蚀的恢复力：中国黄土高原千年记录的Demo。

IF 3.8

PNAS nexus Pub Date : 2026-04-16 eCollection Date: 2026-05-01 DOI: 10.1093/pnasnexus/pgag127

Xunchang J Zhang, Jie Chen, Guobin Liu

{"title":"Humans can rebuild severely eroded resilience: Demo with millennia-long records in China's Loess Plateau.","authors":"Xunchang J Zhang, Jie Chen, Guobin Liu","doi":"10.1093/pnasnexus/pgag127","DOIUrl":"https://doi.org/10.1093/pnasnexus/pgag127","url":null,"abstract":"There exists growing interest in integrating social and ecological sciences to elucidate human-nature interactions from the perspective of social-ecological systems (SES). The compelling logic in the past is that people inevitably harm nature as they use it; however, people have learned to use it while protecting or even improving it. Nowadays though there is a growing emphasis on transformability into a more desirable SES with deliberate human actions rather than adapting to the existing conditions, this theory has not been tested, due to the lack of large-scale and long-term records. The millennia-long records of humans to alter SES in China's Loess Plateau provide a unique means to test ecological theories and heuristic models. Here, we demonstrated human activities can erode ecological resilience or improve it to provide better ecoservices than the pristine. Relative resilience, calculated as a ratio of annual sediment discharge anomaly to the pristine rate, decreased from 0 at the pristine state to -1 in the 1950s due to deforestation and agricultural expansion, whereas increased to about 0.8 at the present by human intervention of environmental slow variables. Building resilience by attending slow variables rather than controlling disturbance should be the goal of adaptive ecosystem management in a SES.","PeriodicalId":74468,"journal":{"name":"PNAS nexus","volume":"5 5","pages":"pgag127"},"PeriodicalIF":3.8,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13135196/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147824492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

User choice, hidden gems, and the quadratic horizon. 用户选择，隐藏的宝石，以及二次元视界。

IF 3.8

PNAS nexus Pub Date : 2026-04-16 eCollection Date: 2026-05-01 DOI: 10.1093/pnasnexus/pgag122

Flavio Chierichetti, Mirko Giacchini, Ravi Kumar, Alessandro Panconesi, Andrew Tomkins

{"title":"User choice, hidden gems, and the quadratic horizon.","authors":"Flavio Chierichetti, Mirko Giacchini, Ravi Kumar, Alessandro Panconesi, Andrew Tomkins","doi":"10.1093/pnasnexus/pgag122","DOIUrl":"https://doi.org/10.1093/pnasnexus/pgag122","url":null,"abstract":"Content platforms typically engage with their users through small recommendation sets of items drawn from an extensive catalog. These sets are curated using machine-learned models optimized to present choices most likely to align with user preferences. We present surprising findings about such platforms. Even with complete information on user preferences within sets of up to k items, these models can only predict preferences within a \"quadratic horizon\" of <math><msup><mi>k</mi> <mn>2</mn></msup> </math> items and might fail to identify the best items in larger sets. To illustrate, we present striking examples where a platform interacting with users through small item sets, despite knowing that one item is favored by millions of users, cannot identify this item with better than random chance. Through both theoretical analysis and studies across various datasets, we demonstrate that \"hidden gems,\" items preferred by many users but invisible to platforms, exist in real-world datasets of moderate size, highlighting a significant gap in current recommendation platforms.","PeriodicalId":74468,"journal":{"name":"PNAS nexus","volume":"5 5","pages":"pgag122"},"PeriodicalIF":3.8,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13132410/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147824446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Animal-origin-free culture improves mitotic response for chromosome aberration analysis of human peripheral blood. 无动物源培养提高了人外周血染色体畸变分析的有丝分裂反应。

IF 3.8

PNAS nexus Pub Date : 2026-04-15 eCollection Date: 2026-04-01 DOI: 10.1093/pnasnexus/pgag120

Yohei Fujishima, Donovan Anderson, Shara Kamakura, Renya Saito, Yuki Tsushima, Ayaka Okimoto, Valerie Swee Ting Goh, Tomisato Miura

{"title":"Animal-origin-free culture improves mitotic response for chromosome aberration analysis of human peripheral blood.","authors":"Yohei Fujishima, Donovan Anderson, Shara Kamakura, Renya Saito, Yuki Tsushima, Ayaka Okimoto, Valerie Swee Ting Goh, Tomisato Miura","doi":"10.1093/pnasnexus/pgag120","DOIUrl":"https://doi.org/10.1093/pnasnexus/pgag120","url":null,"abstract":"The lymphocyte culture method for chromosomal aberration analysis was established in the 1960s, and culture media supplemented with fetal bovine serum (FBS) have been routinely used. However, issues such as lot-to-lot variability, potential contamination risks, and the growing demand for animal-origin-free (AOF) systems have created a need for reliable alternatives. This study evaluated the suitability of serum-free culture media for human peripheral blood chromosome analysis under both clinical-cytogenetic and cytogenetic biodosimetry settings, including the dicentric chromosome (Dic) assay and the cytokinesis-block micronucleus (MN) assay. Cell proliferation markers of mitotic index (MI), binucleated cell frequency, and chromosomal aberration frequencies were compared between conventional RPMI 1640 medium and human plasma-like medium, each tested with or without FBS supplementation in phytohemagglutinin-stimulated blood cultures. Serum-free media demonstrated significantly higher MI values than in RPMI 1640-containing FBS, suggesting that serum supplementation may inhibit cell-cycle progression in 48- and 72-h cultures. While MI increased, the frequencies of Dics and MNs in serum-free conditions were not significantly different from those observed in serum-supplemented cultures. These findings indicate that serum supplementation may not be essential for blood culture media in human peripheral blood chromosome analysis, supporting the transition toward serum-free and AOF systems in cytogenetic applications.","PeriodicalId":74468,"journal":{"name":"PNAS nexus","volume":"5 4","pages":"pgag120"},"PeriodicalIF":3.8,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13123523/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147791656","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Combined administration of interleukin-2 and 18 with anti-PD-L1 antibody induces CCL5-positive CD8 T cells to suppress liver tumors. 白细胞介素-2和白细胞介素- 18联合抗pd - l1抗体可诱导ccl5阳性CD8 T细胞抑制肝脏肿瘤。

IF 3.8

PNAS nexus Pub Date : 2026-04-15 eCollection Date: 2026-04-01 DOI: 10.1093/pnasnexus/pgag113

Masamichi Kimura, Kenzaburo Yamaji, Kenichi Harada, Hideya Kawaji, Jun Imamura, Haruki Okamura, Yoshimasa Tanaka, Michinori Kohara, Kiminori Kimura

{"title":"Combined administration of interleukin-2 and 18 with anti-PD-L1 antibody induces CCL5-positive CD8 T cells to suppress liver tumors.","authors":"Masamichi Kimura, Kenzaburo Yamaji, Kenichi Harada, Hideya Kawaji, Jun Imamura, Haruki Okamura, Yoshimasa Tanaka, Michinori Kohara, Kiminori Kimura","doi":"10.1093/pnasnexus/pgag113","DOIUrl":"https://doi.org/10.1093/pnasnexus/pgag113","url":null,"abstract":"Remarkable progress has been made in cancer immunotherapy, partly because of the development of immune checkpoint inhibitors. However, their efficacy varies across cancer types, with limited response observed in solid tumors, such as hepatocellular carcinoma (HCC). The primary cause of this low efficacy is insufficient infiltration of effector cells, such as cytotoxic CD8+ T cells, into the tumor tissue. This study investigated whether recombinant interleukin (rIL)-2, rIL-18, and antiprogrammed cell death-ligand 1 (αPD-L1) antibody (Ab) could serve as novel immunotherapies for HCC. Multidrug resistance gene 2-deficient mice, a spontaneously occurring liver cancer model associated with aging, were administered rIL-2, rIL-18, and αPD-L1Ab. Antitumor effects were evaluated using computed tomography and serum alpha-fetoprotein levels. Significant tumor shrinkage was observed in the rIL-2+rIL-18+αPD-L1Ab group, but not in the rIL-2+αPD-L1Ab or rIL-18+αPD-L1Ab groups. Concurrent administration of αCD8-neutralizing antibody abolished the antitumor effect, indicating CD8+ T-cell dependency. Spatial gene expression profiling revealed that intratumoral CD8+ effector T cells express and secrete CCL5 after treatment, promoting CD8+ T-cell mobilization to the liver and enhancing antitumor efficacy. Pretreatment with a CCL5 neutralizing antibody suppressed CD8+ cell infiltration into the tumor, eliminating the antitumor effect. The triple combination therapy used in this study promotes the infiltration and maintenance of CD8+ T cells in the liver, suggesting a promising new immunotherapy for HCC.","PeriodicalId":74468,"journal":{"name":"PNAS nexus","volume":"5 4","pages":"pgag113"},"PeriodicalIF":3.8,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13096734/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147791685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0