bluuebunny/crossref_metadata_2025_split huggingface dataset:
Continental Thermal Structure and Carbonate Storage of Subducted Sedimentary Origin Control on Different Increases in Atmospheric CO2 in Late Ediacaran and Jurassic
Authors: Wang Xinxin , Zhao Liang , Yang Jianfeng , Li Jilei , Chen Ling , Sun Baolu 
Published: September 2023

AbstractCarbon release during continental rifting is thought to regulate atmospheric CO2 levels. Supercontinent dispersal‐induced extensional tectonics is similar during the Late Ediacaran and Jurassic, while they exhibit different increases in atmospheric CO2 concentration. The underlying mechanism of distinct CO2 emissions remains to be understood. Here, we conduct petrological‐thermomechanical modeling to show that metamorphic decarbonation and melting of carbonates that are derived from subducted sediments are ubiquitous during continental extension. We find that the hotter lithosphere and deeper storage of these carbonates cause more significant amounts of rift‐related CO2 release through volcanoes and faults. They may cause ∼12%–77% larger decarbonation efficiency, providing an efficient driving mechanism for a ∼31% larger increase in atmospheric CO2 levels during the Late Ediacaran than throughout the Jurassic. The rapid eruption and deposition of recycled carbonatite volcanic ash may contribute to the production of Late Ediacaran marine carbonates with the largest negative δ13C (−12‰).
Geophysically Informed Machine Learning for Improving Rapid Estimation and Short‐Term Prediction of Earth Orientation Parameters
Authors: Kiani Shahvandi Mostafa , Dill Robert , Dobslaw Henryk , Kehm Alexander , Bloßfeld Mathis , Schartner Matthias , Mishra Siddhartha , Soja Benedikt 
Published: September 2023

AbstractRapid provision of Earth orientation parameters (EOPs, here polar motion and dUT1) is indispensable in many geodetic applications and also for spacecraft navigation. There are, however, discrepancies between the rapid EOPs and the final EOPs that have a higher latency but the highest accuracy. To reduce these discrepancies, we focus on a data‐driven approach, present a novel method named ResLearner, and use it in the context of deep ensemble learning. Furthermore, we introduce a geophysically constrained approach for ResLearner. We show that the most important geophysical information to improve the rapid EOPs is the effective angular momentum functions of atmosphere, ocean, land hydrology, and sea level. In addition, semidiurnal, diurnal, and long‐period tides coupled with prograde and retrograde tidal excitations are important features. The influence of some climatic indices on the prediction accuracy of dUT1 is discussed, and El Niño Southern Oscillation is found to be influential. We developed an operational framework, providing the improved EOPs on a daily basis with a prediction window of 63 days to fully cover the latency of final EOPs. We show that under the operational conditions and using the rapid EOPs of the International Earth Rotation and Reference Systems Service (IERS), we achieve improvements as high as 60%, thus significantly reducing the differences between rapid and final EOPs. Furthermore, we discuss how the new final series IERS 20 C04 is preferred over 14 C04. Finally, we compare against EOP hindcast experiments of the European Space Agency, on which ResLearner presents comparable improvements.
Influences of Lateral Boundary Forcings on the 2020 Extreme Meiyu in the Yangtze‐Huaihe River Valley
Authors: Zhu Xiaoyu , Hu Yijia , Sun Xuguang , Zhong Zhong , Ha Yao , Li Yunying 
Published: September 2023

AbstractMeiyu occurs in Yangtze‐Huaihe River valley (YHRV) every summer. Its intensity, distribution, and intraseasonal variation are greatly influenced by atmospheric forcings from different directions, such as the monsoon southwesterlies from the south, the western Pacific subtropical high (WPSH) in the east, the atmospheric longwave activities in the north, the southwest vortex from the west, and so on. In this study, to explore the contributions of the atmospheric forcings from different directions to 2020 extreme Meiyu, Regional Climate Model version 4.6 (RegCM4.6) is employed. A series of sensitivity experiments are conducted with realistic or climatological averaged lateral boundary conditions. The results show that the monsoon westerlies from the south transport moisture and heat to YHRV, converge with the cold air brought by the frequent atmospheric longwave activities in the north, and result in this extreme Meiyu. The frequent cold air from the north can lift warm air, provide unstable conditions, and make the distribution of precipitation similar to the teleconnection pattern in East Asia. The stable WPSH in the east anchors the 2020 Meiyu rainband to the YHTV for a long time. In addition, the contributions of the atmospheric forcings from different directions to evolution of 2020 Meiyu change with time. Before 10 June, the WPSH in the east mainly contributes to the Meiyu evolution. From 11 June to 3 July, the combined effects of atmospheric forcings from the south and north are dominant. From 3 July to 10 July, the cold air from the north plays a major role.
The PFC-LH-VTA pathway contributes to social deficits in IRSp53-mutant mice
Authors: Noh Young Woo , Kim Yangsik , Lee Soowon , Kim Yeonghyeon , Shin Jae Jin , Kang Hyojin , Kim Il Hwan , Kim Eunjoon 
Published: September 2023

AbstractDopamine (DA) neurons in the ventral tegmental area (VTA) promote social brain functions by releasing DA onto nucleus accumbens neurons, but it remains unclear how VTA neurons communicate with cortical neurons. Here, we report that the medial prefrontal cortex (mPFC)-lateral hypothalamus (LH)-VTA pathway contributes to social deficits in mice with IRSp53 deletion restricted to cortical excitatory neurons (Emx1-Cre;Irsp53fl/fl mice). LH-projecting mutant mPFC neurons display abnormally increased excitability involving decreased potassium channel gene expression, leading to excessive excitatory synaptic input to LH-GABA neurons. A circuit-specific IRSp53 deletion in LH-projecting mPFC neurons also increases neuronal excitability and induces social deficits. LH-GABA neurons with excessive mPFC excitatory synaptic input show a compensatory decrease in excitability, weakening the inhibitory LHGABA-VTAGABA pathway and subsequently over-activating VTA-GABA neurons and over-inhibiting VTA-DA neurons. Accordingly, optogenetic activation of the LHGABA-VTAGABA pathway improves social deficits in Emx1-Cre;Irsp53fl/fl mice. Therefore, the mPFC-LHGABA-VTAGABA-VTADA pathway contributes to the social deficits in Emx1-Cre;Irsp53fl/fl mice.
A first-in-human phase 1 study of nofazinlimab, an anti-PD-1 antibody, in advanced solid tumors and in combination with regorafenib in metastatic colorectal cancer
Authors: Day Daphne , Park John J. , Coward Jermaine , Markman Ben , Lemech Charlotte , Kuo James C. , Prawira Amy , Brown Michael P. , Bishnoi Sarwan , Kotasek Dusan , Strother R. Matthew , Cosman Rasha , Su Rila , Ma Yiding , Yue Zenglian , Hu Hui-han , Wu Rachel , Li Peiqi , Tse Archie N. 
Published: September 2023

AbstractBackgroundWe assessed nofazinlimab, an anti-PD-1 antibody, in solid tumors and combined with regorafenib in metastatic colorectal cancer (mCRC).MethodsThis phase 1 study comprised nofazinlimab dose escalation (phase 1a) and expansion (phase 1b), and regorafenib dose escalation (80 or 120 mg QD, days 1–21 of 28-day cycles) combined with 300-mg nofazinlimab Q4W (part 2a) to determine safety, efficacy, and RP2D.ResultsIn phase 1a (N = 21), no dose-limiting toxicity occurred from 1 to 10 mg/kg Q3W, with 200 mg Q3W determined as the monotherapy RP2D. In phase 1b (N = 87), 400-mg Q6W and 200-mg Q3W regimens were found comparable. In part 2a (N = 14), both regimens were deemed plausible RP2Ds. Fatigue was the most frequent treatment-emergent adverse event (AE) in this study. Any-grade and grade 3/4 nofazinlimab-related AEs were 71.4% and 14.3%, 56.3% and 5.7%, and 57.1% and 21.4% in phases 1a, 1b, and part 2a, respectively. ORRs were 14.3% and 25.3% in phases 1a and 1b, respectively. In part 2a, no patients had radiological responses.ConclusionsNofazinlimab monotherapy was well tolerated and demonstrated preliminary anti-tumor activity in multiple tumor types. Regorafenib plus nofazinlimab had a manageable safety profile but was not associated with any response in mCRC.Clinical trial registr ationClinicaltrials.gov (NCT03475251).
SCF and IL-33 regulate mouse mast cell phenotypic and functional plasticity supporting a pro-inflammatory microenvironment
Authors: Molfetta Rosa , Lecce Mario , Milito Nadia D. , Putro Erisa , Pietropaolo Giuseppe , Marangio Caterina , Scarno Gianluca , Moretti Marta , De Smaele Enrico , Santini Tiziana , Bernardini Giovanni , Sciumè Giuseppe , Santoni Angela , Paolini Rossella 
Published: September 2023

AbstractMast cells (MCs) are multifaceted innate immune cells often present in the tumor microenvironment (TME). Several recent findings support their contribution to the transition from chronic inflammation to cancer. However, MC-derived mediators can either favor tumor progression, inducing the spread of the tumor, or exert anti-tumorigenic functions, limiting tumor growth. This apparent controversial role likely depends on the plastic nature of MCs that under different microenvironmental stimuli can rapidly change their phenotype and functions. Thus, the exact effect of unique MC subset(s) during tumor progression is far from being understood. Using a murine model of colitis-associated colorectal cancer, we initially characterized the MC population within the TME and in non-lesional colonic areas, by multicolor flow cytometry and confocal microscopy. Our results demonstrated that tumor-associated MCs harbor a main connective tissue phenotype and release high amounts of Interleukin (IL)-6 and Tumor Necrosis Factor (TNF)-α. This MC phenotype correlates with the presence of high levels of Stem Cell Factor (SCF) and IL-33 inside the tumor. Thus, we investigated the effect of SCF and IL-33 on primary MC cultures and underscored their ability to shape MC phenotype eliciting the production of pro-inflammatory cytokines. Our findings support the conclusion that during colonic transformation a sustained stimulation by SCF and IL-33 promotes the accumulation of a prevalent connective tissue-like MC subset that through the secretion of IL-6 and TNF-α maintains a pro-inflammatory microenvironment.
Upper-plate conduits linked to plate boundary that hosts slow earthquakes
Authors: Arai Ryuta , Miura Seiichi , Nakamura Yasuyuki , Fujie Gou , Kodaira Shuichi , Kaiho Yuka , Mochizuki Kimihiro , Nakata Rie , Kinoshita Masataka , Hashimoto Yoshitaka , Hamada Yohei , Okino Kyoko 
Published: September 2023

AbstractIn shallow subduction zones, fluid behavior impacts various geodynamic processes capable of regulating slip behaviors and forming mud volcanoes. However, evidence of structures that control the fluid transfer within an overriding plate is limited and the physical properties at the source faults of slow earthquakes are poorly understood. Here we present high-resolution seismic velocity models and reflection images of the Hyuga-nada area, Japan, where the Kyushu-Palau ridge subducts. We image distinct kilometer-wide columns in the upper plate with reduced velocities that extend vertically from the seafloor down to 10–13 km depth. We interpret the low-velocity columns as damaged zones caused by seamount subduction and suggest that they serve as conduits, facilitating vertical fluid migration from the plate boundary. The lateral variation in upper-plate velocity and seismic reflectivity along the plate boundary correlates with the distribution of slow earthquakes, indicating that the upper-plate drainage system controls the complex pattern of seismic slip at subduction faults.
Genetic reversal of the globin switch concurrently modulates both fetal and sickle hemoglobin and reduces red cell sickling
Authors: De Souza Daniel C. , Hebert Nicolas , Esrick Erica B. , Ciuculescu M. Felicia , Archer Natasha M. , Armant Myriam , Audureau Étienne , Brendel Christian , Di Caprio Giuseppe , Galactéros Frédéric , Liu Donghui , McCabe Amanda , Morris Emily , Schonbrun Ethan , Williams Dillon , Wood David K. , Williams David A. , Bartolucci Pablo , Higgins John M. 
Published: September 2023

AbstractWe previously reported initial clinical results of post-transcriptional gene silencing of BCL11A expression (NCT 03282656) reversing the fetal to adult hemoglobin switch. A goal of this approach is to increase fetal hemoglobin (HbF) expression while coordinately reducing sickle hemoglobin (HbS) expression. The resulting combinatorial effect should prove effective in inhibiting HbS polymerization at lower physiologic oxygen values thereby mitigating disease complications. Here we report results of exploratory single-cell analysis of patients in which BCL11A is targeted molecularly and compare results with cells of patients treated with hydroxyurea (HU), the current standard of care. We use single-cell assays to assess HbF, HbS, oxygen saturation, and hemoglobin polymer content in RBCs for nine gene therapy trial subjects (BCLshmiR, median HbF% = 27.9) and compare them to 10 HU-treated subjects demonstrating high and comparable levels of HbF (HU High Responders, median HbF% = 27.0). All BCL11A patients achieved the primary endpoint for NCT 03282656, which was defined by an absolute neutrophil count greater than or equal to 0.5 × 109 cells/L for three consecutive days, achieved within 7 weeks following infusion. Flow cytometric assessment of single-RBC HbF and HbS shows fewer RBCs with high HbS% that would be most susceptible to sickling in BCLshmiR vs. HU High Responders: median 42% of RBCs with HbS%>70% in BCLshmiR vs. 61% in HU High Responders (p = 0.004). BCLshmiR subjects also demonstrate more RBCs resistant to HbS polymerization at lower physiologic oxygen tension: median 32% vs. 25% in HU High Responders (p = 0.006). Gene therapy-induced BCL11A down-regulation reverses the fetal-to-adult hemoglobin switch and induces RBCs with higher HbF%, lower HbS%, and greater resistance to deoxygenation-induced polymerization in clinical trial subjects compared with a cohort of highly responsive hydroxyurea-treated subjects.
Conserved roles for the dynein intermediate chain and Ndel1 in assembly and activation of dynein
Authors: Okada Kyoko , Iyer Bharat R. , Lammers Lindsay G. , Gutierrez Pedro A. , Li Wenzhe , Markus Steven M. , McKenney Richard J. 
Published: September 2023

AbstractProcessive transport by the microtubule motor cytoplasmic dynein requires the regulated assembly of a dynein-dynactin-adapter complex. Interactions between dynein and dynactin were initially ascribed to the dynein intermediate chain N-terminus and the dynactin subunit p150Glued. However, recent cryo-EM structures have not resolved this interaction, questioning its importance. The intermediate chain also interacts with Nde1/Ndel1, which compete with p150Glued for binding. We reveal that the intermediate chain N-terminus is a critical evolutionarily conserved hub that interacts with dynactin and Ndel1, the latter of which recruits LIS1 to drive complex assembly. In additon to revealing that the intermediate chain N-terminus is likely bound to p150Glued in active transport complexes, our data support a model whereby Ndel1-LIS1 must dissociate prior to LIS1 being handed off to dynein in temporally discrete steps. Our work reveals previously unknown steps in the dynein activation pathway, and provide insight into the integrated activities of LIS1/Ndel1 and dynactin/cargo-adapters.
Predictors of the post-COVID condition following mild SARS-CoV-2 infection
Authors: Reme B-A. , Gjesvik J. , Magnusson K. 
Published: September 2023

AbstractWhereas the nature of the post-COVID condition following mild acute COVID-19 is increasingly well described in the literature, knowledge of its risk factors, and whether it can be predicted, remains limited. This study, conducted in Norway, uses individual-level register data from 214,667 SARS-CoV-2 infected individuals covering a range of demographic, socioeconomic factors, as well as cause-specific healthcare utilization in the years prior to infection to assess the risk of post-COVID complaints ≥3 months after testing positive. We find that the risk of post-COVID was higher among individuals who prior to infection had been diagnosed with psychological (OR = 2.12, 95% CI 1.84–2.44), respiratory (OR = 2.03, 95% CI 1.78–2.32), or general and unspecified health problems (OR = 1.78, 95% CI 1.52–2.09). To assess the predictability of post-COVID after mild initial disease, we use machine learning methods and find that pre-infection characteristics, combined with information on the SARS-CoV-2 virus type and vaccine status, to a considerable extent (AUC = 0.79, 95% CI 0.75–0.81) could predict the occurrence of post-COVID complaints in our sample.
Genome-wide probing of eukaryotic nascent RNA structure elucidates cotranscriptional folding and its antimutagenic effect
Authors: Yu Gongwang , Liu Yao , Li Zizhang , Deng Shuyun , Wu Zhuoxing , Zhang Xiaoyu , Chen Wenbo , Yang Junnan , Chen Xiaoshu , Yang Jian-Rong 
Published: September 2023

AbstractThe transcriptional intermediates of RNAs fold into secondary structures with multiple regulatory roles, yet the details of such cotranscriptional RNA folding are largely unresolved in eukaryotes. Here, we present eSPET-seq (Structural Probing of Elongating Transcripts in eukaryotes), a method to assess the cotranscriptional RNA folding in Saccharomyces cerevisiae. Our study reveals pervasive structural transitions during cotranscriptional folding and overall structural similarities between nascent and mature RNAs. Furthermore, a combined analysis with genome-wide R-loop and mutation rate approximations provides quantitative evidence for the antimutator effect of nascent RNA folding through competitive inhibition of the R-loops, known to facilitate transcription-associated mutagenesis. Taken together, we present an experimental evaluation of cotranscriptional folding in eukaryotes and demonstrate the antimutator effect of nascent RNA folding. These results suggest genome-wide coupling between the processing and transmission of genetic information through RNA folding.
Metal-organic framework template-guided electrochemical lithography on substrates for SERS sensing applications
Authors: Lu Youyou , Zhang Xuan , Zhao Liyan , Liu Hong , Yan Mi , Zhang Xiaochen , Mochizuki Kenji , Yang Shikuan 
Published: September 2023

AbstractThe templating method holds great promise for fabricating surface nanopatterns. To enhance the manufacturing capabilities of complex surface nanopatterns, it is important to explore new modes of the templates beyond their conventional masking and molding modes. Here, we employed the metal-organic framework (MOF) microparticles assembled monolayer films as templates for metal electrodeposition and revealed a previously unidentified guiding growth mode enabling the precise growth of metallic films exclusively underneath the MOF microparticles. The guiding growth mode was induced by the fast ion transportation within the nanochannels of the MOF templates. The MOF template could be repeatedly used, allowing for the creation of identical metallic surface nanopatterns for multiple times on different substrates. The MOF template-guided electrochemical growth mode provided a robust route towards cost-effective fabrication of complex metallic surface nanopatterns with promising applications in metamaterials, plasmonics, and surface-enhanced Raman spectroscopy (SERS) sensing fields.
Efficiently accelerated free electrons by metallic laser accelerator
Authors: Zheng Dingguo , Huang Siyuan , Li Jun , Tian Yuan , Zhang Yongzhao , Li Zhongwen , Tian Huanfang , Yang Huaixin , Li Jianqi 
Published: September 2023

AbstractStrong electron-photon interactions occurring in a dielectric laser accelerator provide the potential for development of a compact electron accelerator. Theoretically, metallic materials exhibiting notable surface plasmon-field enhancements can possibly generate a high electron acceleration capability. Here, we present a design for metallic material-based on-chip laser-driven accelerators that show a remarkable electron acceleration capability, as demonstrated in ultrafast electron microscopy investigations. Under phase-matching conditions, efficient and continuous acceleration of free electrons on a periodic nanostructure can be achieved. Importantly, an asymmetric spectral structure in which the vast majority of the electrons are in the energy-gain states has been obtained by means of a periodic bowtie-structure accelerator. Due to the presence of surface plasmon enhancement and nonlinear optical effects, the maximum acceleration gradient can reach as high as 0.335 GeV/m. This demonstrates that metallic laser accelerator could provide a way to develop compact accelerators on chip.
Traffic light optimization using non-dominated sorting genetic algorithm (NSGA2)
Authors: Leal Samara Soares , de Almeida Paulo Eduardo M. 
Published: September 2023

AbstractTraffic congestion is a major concern in urban centers, as it can affect society, the environment, and the economy. There are many studies on the use of computational intelligence (CI) to improve mobility in urban centers. Some of these researches focus on developing strategies for traffic light programming, since traffic coordination is complex due to its many parameters, variables, and dynamic behavior, and also an inefficient traffic control plan can lead to increased delays and contribute to traffic congestion. Although there are many works in the literature on strategies for traffic control, there are still some contributions and gaps to be filled, especially because some studies do not consider the automatic optimization of traffic signals in real time, that is, according to the demand of vehicles on the roads, considering multiple objectives and the use of a network of intersections in their experiments. In addition, some of the proposed models are not independent of simulation to evaluate the solutions of CI algorithms, resulting in a more complex deployment in real situations. In this context, this paper presents a new method to optimize traffic light plan in a network of intersections and in real time, called Active Control of Traffic Signals (ACTS) associated with the Non-Dominated Sorting Genetic Algorithm, considering multiple objectives in the optimization process (minimizing the average delay time and the number of vehicles stops per cycle). To test the applicability of the model, a real dataset of vehicle demand collected by the Company of Transport and Traffic of Belo Horizonte (BHTrans) is loaded into the AIMSUN simulator, then the method is applied and compared with the current traffic control plan used by BHTrans. The results show that the ACTS method reduces the average vehicle delay by almost half compared to the results obtained with the current solution used by BHTrans. In real life, this means less time spent in traffic, which promotes faster traffic flow, reducing traffic congestions.