bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Toy Model to Investigate Stability of AI‐Based Dynamical Systems
Authors: Balogh B. , Saint‐Martin D. , Ribes A. 
Published: April 2021

AbstractThe development of atmospheric parameterizations based on neural networks is often hampered by numerical instability issues. Previous attempts to replicate these issues in a toy model have proven ineffective. We introduce a new toy model for atmospheric dynamics, which consists in an extension of the Lorenz’63 model to a higher dimension. While feedforward neural networks trained on a single orbit can easily reproduce the dynamics of the Lorenz’63 model, they fail to reproduce the dynamics of the new toy model, leading to unstable trajectories. Instabilities become more frequent as the dimension of the new model increases, but are found to occur even in very low dimension. Training the feedforward neural network on a different learning sample, based on Latin Hypercube Sampling, solves the instability issue. Our results suggest that the design of the learning sample can significantly influence the stability of dynamical systems driven by neural networks.
On the Terrestrial Gamma‐Ray Flashes Preceding Narrow Bipolar Events
Authors: Zhang Hongbo , Lu Gaopeng , Lyu Fanchao , Xiong Shaolin , Ahmad Mohd Riduan , Yi Qibin , Li Dongshuai , Xian Tao , Yang Jing , Liu Feifan , Zhu Baoyou , Pu Yunjiao , Cummer Steven A. , Briggs Michael S. , Qie Xiushu 
Published: April 2021

AbstractNarrow bipolar events (NBEs) are occasionally reported to occur within a few ms after Terrestrial Gamma‐ray Flashes (TGFs), while the formation mechanism remains mysterious partially due to the lack of sufficient observations. Here, nine more TGFs of this scenario are reported with concurrent LF sferics and lightning location data. The gamma‐ray production in these TGFs preceded the occurrence of NBEs by a minimum of 60 µs up to 13.5 ms, and no other fast leader discharge was found within 20 ms before the TGF. The TGF‐preceded positive NBEs occurred at altitudes of 8.6–11 km in thunderstorms, likely in the high electric field (E‐field) region of lightning initiation. The analyses show that the NBE‐preceding TGFs bear harder energy spectrum with larger proportion of high‐energy photons than EIP‐related TGFs produced in association with lightning leader. Our findings support the relativistic feedback mechanism of gamma‐ray generation in the large‐scale thunderstorm E‐field.
First Observation of the Oxygen 630 nm Emission in the Martian Dayglow
Authors: Gérard J.‐C. , Aoki S. , Gkouvelis L. , Soret L. , Willame Y. , Thomas I. R. , Depiesse C. , Ristic B. , Vandaele A. C. , Hubert B. , Daerden F. , Patel M. R. , López‐Moreno J.‐J. , Bellucci G. , Mason J. P. , López‐Valverde M. A. 
Published: April 2021

AbstractFollowing the recent detection of the oxygen green line airglow on Mars, we have improved the statistical analysis of the data recorded by the NOMAD/UVIS instrument on board the ExoMars Trace Gas Orbiter mission by summing up hundreds of spectra to increase the signal‐to‐noise ratio. This led to the observation of the OI 630 nm emission, the first detection in a planetary atmosphere outside the Earth. The average limb profile shows a broad peak intensity of 4.8 kR near 150 km. Comparison with a photochemical model indicates that it is well predicted by current photochemistry, considering the sources of uncertainty. The red/green line intensity ratio decreases dramatically with altitude as a consequence of the efficient quenching of O(1D) by CO2. Simultaneous observations of the green and red dayglow will provide information on variations in the thermosphere in response to seasonal changes and the effects of solar events.
Diachronous Growth of the Northern Tibetan Plateau Derived From Flexural Modeling
Authors: Wang Lin , Cheng Feng , Zuza Andrew V. , Jolivet Marc , Liu Yiduo , Guo Zhaojie , Li Xiangzhong , Zhang Changhao 
Published: April 2021

AbstractThe early Cenozoic topography of the northern Tibetan plateau remains enigmatic because of the paucity of independent paleoelevation constraints. Long‐held views of northward propagating deformation imply a low Paleogene elevation, but this prediction is speculative. We apply flexural modeling to reconstructed Paleogene isopach data obtained from the Qaidam basin, which requires a larger topographic load in the Qilian Shan and a smaller load in the Eastern Kunlun Shan. Incorporating knowledge of proto‐Paratethys marine incursions in the Paleogene Qaidam basin, we infer a topographically low (0.4–1.0 km) Eastern Kunlun Shan and a higher (0.4–1.5 km) Qilian Shan during the Paleogene. This implied paleo‐relief contrasts with previous predictions and suggests more recently, Neogene surface uplift in the Eastern Kunlun Shan has been more significant than in Qilian Shan, highlighting diachronous growth of the northern Tibetan plateau. The low‐moderate paleoelevation implies a warmer and more humid climate in Northern Tibet during the Paleogene.
Role of Intense Arctic Storm in Accelerating Summer Sea Ice Melt: An In Situ Observational Study
Authors: Peng Liran , Zhang Xiangdong , Kim Joo‐Hong , Cho Kyoung‐Ho , Kim Baek‐Min , Wang Zhaomin , Tang Han 
Published: April 2021

AbstractIntense storms have been more frequently observed in the Arctic during recent years, in coincidence with extreme sea ice loss events. However, it is still not fully understood how storms drive such events due to deficient observations and modeling discrepancies. Here we address this problem by analyzing in situ observations acquired during an Arctic expedition, which uniquely captured an intense storm in summer 2016. The result shows a pronounced acceleration of sea ice loss during the storm process. Diagnostic analysis indicates a net energy loss at the ice surface, not supporting the accelerated melting. Although the open water surface gained net heat energy, it was insufficient to increase the mixed‐layer temperature to the observed values. Dynamic analysis suggests that storm‐driven increase in ocean mixing and upward Ekman pumping of the Pacific‐origin warm water tremendously increased oceanic heat flux. The thermal advection by the Ekman pumping led to a warmed mixed layer by 0.05°C–0.12°C and, in consequence, an increased basal sea ice melt rate by 0.1–1.7 cm day−1.
Aviation Contrail Cirrus and Radiative Forcing Over Europe During 6 Months of COVID‐19
Authors: Schumann U. , Bugliaro L. , Dörnbrack A. , Baumann R. , Voigt C. 
Published: April 2021

AbstractThe COVID‐19 pandemic led to a 72% reduction of air traffic over Europe in March–August 2020 compared to 2019. Modeled contrail cover declined similarly, and computed mean instantaneous radiative contrail forcing dropped regionally by up to 0.7 W m−2. Here, model predictions of cirrus optical thickness and the top‐of‐atmosphere outgoing longwave and reflected shortwave irradiances are tested by comparison to Meteosat‐SEVIRI‐derived data. The agreement between observations and modeled data is slightly better when modeled contrail cirrus contributions are included. The spatial distributions and diurnal cycles of the differences in these data between 2019 and 2020 are partially caused by differences in atmospheric and surface conditions, particularly for solar radiation in the spring of 2020. Aviation signals become discernible in the observed differences of these data between 2019 and 2020 when subtracting numerical weather prediction model results that approximate the atmosphere and surface conditions without contrails.
Characteristics of Low‐Harmonic Magnetosonic Waves in the Earth's Inner Magnetosphere
Authors: Teng S. , Liu N. , Ma Q. , Tao X. 
Published: April 2021

AbstractMagnetosonic (MS) waves are electromagnetic waves that play important roles in the acceleration and scattering of radiation belt electrons. However, previous statistical analyses of the global MS wave distribution were mainly restricted to magnetic field measurements. In this study, we first report a low‐harmonic MS wave event observed only by the electric field instrument in Van Allen Probes. The MS wave frequencies follow the local proton gyrofrequency (fcp), which suggests the characteristics of nearly local generation. We further statistically investigate similar wave events using Van Allen Probes data. The identified MS wave power exhibits peaks between 4fcp and 10fcp, regardless of the L‐shell, but it shows a dependence on magnetic local time. This work is supplemental to previous MS wave frequency spectra and provides new insights to better understand the source region of MS waves in the Earth's magnetosphere.
Prokaryotic taxonomy and nomenclature in the age of big sequence data
Authors: Hugenholtz Philip , Chuvochina Maria , Oren Aharon , Parks Donovan H , Soo Rochelle M 
Published: April 2021

Abstract
The classification of life forms into a hierarchical system (taxonomy) and the application of names to this hierarchy (nomenclature) is at a turning point in microbiology. The unprecedented availability of genome sequences means that a taxonomy can be built upon a comprehensive evolutionary framework, a longstanding goal of taxonomists. However, there is resistance to adopting a single framework to preserve taxonomic freedom, and ever increasing numbers of genomes derived from uncultured prokaryotes threaten to overwhelm current nomenclatural practices, which are based on characterised isolates. The challenge ahead then is to reach a consensus on the taxonomic framework and to adapt and scale the existing nomenclatural code, or create a new code, to systematically incorporate uncultured taxa into the chosen framework.
miR-30d suppresses proliferation and invasiveness of pancreatic cancer by targeting the SOX4/PI3K-AKT axis and predicts poor outcome
Authors: Xu Xiaodong , Zong Ke , Wang Xinxing , Dou Dongwei , Lv Pengwei , Zhang Zhe , Li Hongwen 
Published: April 2021

AbstractAberrant expression of miR-30d is associated with the development and progression of several human cancers. However, its biological roles and underlying mechanisms in pancreatic cancer are largely unknown. The expression of miR-30d in pancreatic cancer was evaluated in public databases and further valuated by real-time quantitative PCR, western blot, and immunohistochemistry in a cohort of pancreatic cancer patients. The role of miR-30d in the proliferation and metastasis of pancreatic cancer cells was determined using in vitro and in vivo assays. Bioinformatics analyses were performed to examine potential target genes of miR-30d. Luciferase reporter assay and functional rescue experiments were used to elucidate the mechanisms of miR-30d. miR-30d was found frequently decreased in pancreatic cancer compared with nontumor tissues, and downregulation of miR-30d predicted poor prognosis and early relapse of pancreatic cancer patients. Overexpression of miR-30d significantly repressed the growth and metastasis of pancreatic cancer cells both in vitro and in vivo. Bioinformatics analyses identified sex-determining region Y-box 4 (SOX4) as a target gene of miR-30d. Mechanically, miR-30d exerted its tumor suppressive effect by directly targeting SOX4, which caused inhibition of the PI3K-AKT signaling pathway. Overexpression of SOX4 partially antagonized the inhibitory effects of miR-30d. Our study demonstrated that dysregulation of the miR-30d/SOX4/PI3K-AKT axis promotes the development and progression of pancreatic cancer. These findings suggest miR-30d as a promising and reliable therapeutic target for pancreatic cancer.
TFAP2A potentiates lung adenocarcinoma metastasis by a novel miR-16 family/TFAP2A/PSG9/TGF-β signaling pathway
Authors: Xiong Yanlu , Feng Yangbo , Zhao Jinbo , Lei Jie , Qiao Tianyun , Zhou Yongsheng , Lu Qiang , Jiang Tao , Jia Lintao , Han Yong 
Published: April 2021

AbstractTranscription factor AP-2α (TFAP2A) was previously regarded as a critical regulator during embryonic development, and its mediation in carcinogenesis has received intensive attention recently. However, its role in lung adenocarcinoma (LUAD) has not been fully elucidated. Here, we tried to investigate TFAP2A expression profiling, clinical significance, biological function and molecular underpinnings in LUAD. We proved LUAD possessed universal TFAP2A high expression, indicating a pervasively poorer prognosis in multiple independent datasets. Then we found TFAP2A was not indispensable for LUAD proliferation, and exogenous overexpression even caused repression. However, we found TFAP2A could potently promote LUAD metastasis possibly by triggering epithelial–mesenchymal transition (EMT) in vitro and in vivo. Furthermore, we demonstrated TFAP2A could transactivate Pregnancy-specific glycoprotein 9 (PSG9) to enhance transforming growth factor β (TGF-β)-triggering EMT in LUAD. Meanwhile, we discovered suppressed post-transcriptional silencing of miR-16 family upon TFAP2A partly contributed to TFAP2A upregulation in LUAD. In clinical specimens, we also validated cancer-regulating effect of miR-16 family/TFAP2A/PSG9 axis, especially for lymph node metastasis of LUAD. In conclusion, we demonstrated that TFAP2A could pivotally facilitate LUAD progression, possibly through a novel pro-metastasis signaling pathway (miR-16 family/TFAP2A/PSG9/ TGF-β).
Development of a bispecific immune engager using a recombinant malaria protein
Authors: Nordmaj Mie A. , Roberts Morgan E. , Sachse Emilie S. , Dagil Robert , Andersen Anne Poder , Skeltved Nanna , Grunddal Kaare V. , Erdoğan Sayit Mahmut , Choudhary Swati , Gustsavsson Tobias , Ørum-Madsen Maj Sofie , Moskalev Igor , Tian Weihua , Yang Zhang , Clausen Thomas M. , Theander Thor G. , Daugaard Mads , Nielsen Morten A. , Salanti Ali 
Published: April 2021

AbstractAs an immune evasion and survival strategy, thePlasmodium falciparummalaria parasite has evolved a protein named VAR2CSA. This protein mediates sequestration of infected red blood cells in the placenta through the interaction with a unique carbohydrate abundantly and exclusively present in the placenta. Cancer cells were found to share the same expression of this distinct carbohydrate, termed oncofetal chondroitin sulfate on their surface. In this study we have used a protein conjugation system to produce a bispecific immune engager, V-aCD3, based on recombinant VAR2CSA as the cancer targeting moiety and an anti-CD3 single-chain variable fragment linked to a single-chain Fc as the immune engager. Conjugation of these two proteins resulted in a single functional moiety that induced immune mediated killing of a broad range of cancer cells in vitro and facilitated tumor arrest in an orthotopic bladder cancer xenograft model.
Circular RNA hsa_circ_101555 promotes hepatocellular carcinoma cell proliferation and migration by sponging miR-145-5p and regulating CDCA3 expression
Authors: Gu Xiaoguang , Zhang Jianan , Ran Yajuan , Pan Hena , Jia JinHong , Zhao Ying , Zhao Xijuan , Li Wendi , Song Shasha , Yu Xiufeng 
Published: April 2021

AbstractCircular RNAs have been reported to play significant roles in regulating pathophysiological processes while also guiding clinical diagnosis and treatment of hepatocellular carcinoma (HCC). However, only a few circRNAs have been identified thus far. Herein, we investigated the role of a specific closed-loop structure of hsa_circ_101555 that was generated by back-splicing of the host gene casein kinase 1 gamma 1 (CSNK1G1) in the development and proliferation of HCC. We investigated the expression of Hsa_circ_101555 in HCC and normal tissues using bioinformatics. The expression level of hsa_circ_101555 was further detected by fluorescence in situ hybridization and qRT-PCR in ten HCC patients. Transwell, migration, WST-1 assays, and colony formation assays were used to evaluate the role of hsa_circ_101555 in HCC development and proliferation. The regulatory mechanisms of hsa_circ_101555 in miR-145-5p and CDCA3 were determined by dual luciferase reporter assay. A mouse xenograft model was also used to determine the effect of hsa_circ_101555 on HCC growth in vivo. hsa_circ_101555 showed greater stability than the linear RNA; while in vitro and in vivo results demonstrated that hsa_circ_101555 silencing significantly suppressed cell proliferation, migration, and invasion of HCC cells. Rescue experiments further demonstrated that suppression of miR-145-5p significantly attenuated the biological effects of hsa_circ_101555 knockdown in HCC cells. We also identified a putative oncogene CDCA3 as a potential miR-145-5p target. Thus, our results demonstrated that hsa_circ_101555 might function as a competing endogenous RNA of miR-145-5p to upregulate CDCA3 expression in HCC. These findings suggest that hsa_circ_101555 may be a potential therapeutic target for patients with HCC.
C3G downregulation induces the acquisition of a mesenchymal phenotype that enhances aggressiveness of glioblastoma cells
Authors: Manzano Sara , Gutierrez-Uzquiza Alvaro , Bragado Paloma , Sequera Celia , Herranz Óscar , Rodrigo-Faus María , Jauregui Patricia , Morgner Stephanie , Rubio Ignacio , Guerrero Carmen , Porras Almudena 
Published: April 2021

AbstractGlioblastoma (GBM) is the most aggressive tumor from the central nervous system (CNS). The current lack of efficient therapies makes essential to find new treatment strategies. C3G, a guanine nucleotide exchange factor for some Ras proteins, plays a dual role in cancer, but its function in GBM remains unknown. Database analyses revealed a reduced C3G mRNA expression in GBM patient samples. C3G protein levels were also decreased in a panel of human GBM cell lines as compared to astrocytes. Based on this, we characterized C3G function in GBM using in vitro and in vivo human GBM models. We report here that C3G downregulation promoted the acquisition of a more mesenchymal phenotype that enhanced the migratory and invasive capacity of GBM cells. This facilitates foci formation in anchorage-dependent and -independent growth assays and the generation of larger tumors in xenografts and chick chorioallantoic membrane (CAM) assays, but with a lower cell density, as proliferation was reduced. Mechanistically, C3G knock-down impairs EGFR signaling by reducing cell surface EGFR through recycling inhibition, while upregulating the activation of several other receptor tyrosine kinases (RTKs) that might promote invasion. In particular, FGF2, likely acting through FGFR1, promoted invasion of C3G-silenced GBM cells. Moreover, ERKs mediate this invasiveness, both in response to FGF2- and serum-induced chemoattraction. In conclusion, our data show the distinct dependency of GBM tumors on C3G for EGF/EGFR signaling versus other RTKs, suggesting that assessing C3G levels may discriminate GBM patient responders to different RTK inhibition protocols. Hence, patients with a low C3G expression might not respond to EGFR inhibitors.
Synergistic effect of the TLR5 agonist CBLB502 and its downstream effector IL-22 against liver injury
Authors: Melin Nicolas , Sánchez-Taltavull Daniel , Fahrner René , Keogh Adrian , Dosch Michel , Büchi Isabel , Zimmer Yitzhak , Medová Michaela , Beldi Guido , Aebersold Daniel M. , Candinas Daniel , Stroka Deborah 
Published: April 2021

AbstractThe toll-like receptor 5 (TLR5) agonist, CBLB502/Entolimod, is a peptide derived from bacterial flagellin and has been shown to protect against radiation-induced tissue damage in animal models. Here we investigated the protective mechanism of CBLB502 in the liver using models of ischemia-reperfusion injury and concanavalin A (ConA) induced immuno-hepatitis. We report that pretreatment of mice with CBLB502 provoked a concomitant activation of NF-κB and STAT3 signaling in the liver and reduced hepatic damage in both models. To understand the underlying mechanism, we screened for cytokines in the serum of CBLB502 treated animals and detected high levels of IL-22. There was no transcriptional upregulation of IL-22 in the liver, rather it was found in extrahepatic tissues, mainly the colon, mesenteric lymph nodes (MLN), and spleen. RNA-seq analysis on isolated hepatocytes demonstrated that the concomitant activation of NF-κB signaling by CBLB502 and STAT3 signaling by IL-22 produced a synergistic cytoprotective transcriptional signature. In IL-22 knockout mice, the loss of IL-22 resulted in a decrease of hepatic STAT3 activation, a reduction in the cytoprotective signature, and a loss of hepatoprotection following ischemia-reperfusion-induced liver injury. Taken together, these findings suggest that CBLB502 protects the liver by increasing hepatocyte resistance to acute liver injury through the cooperation of TLR5-NF-κB and IL-22-STAT3 signaling pathways.
MCPIP1-mediated NFIC alternative splicing inhibits proliferation of triple-negative breast cancer via cyclin D1-Rb-E2F1 axis
Authors: Chen Fengxia , Wang Qingqing , Yu Xiaoyan , Yang Ningning , Wang Yuan , Zeng Yangyang , Zheng Zhewen , Zhou Fuxiang , Zhou Yunfeng 
Published: April 2021

AbstractTriple-negative breast cancer (TNBC) is the most aggressive subtype with the worst prognosis and the highest metastatic and recurrence potential, which represents 15–20% of all breast cancers in Chinese females, and the 5-year overall survival rate is about 80% in Chinese women. Recently, emerging evidence suggested that aberrant alternative splicing (AS) plays a crucial role in tumorigenesis and progression. AS is generally controlled by AS-associated RNA binding proteins (RBPs). Monocyte chemotactic protein induced protein 1 (MCPIP1), a zinc finger RBP, functions as a tumor suppressor in many cancers. Here, we showed that MCPIP1 was downregulated in 80 TNBC tissues and five TNBC cell lines compared to adjacent paracancerous tissues and one human immortalized breast epithelial cell line, while its high expression levels were associated with increased overall survival in TNBC patients. We demonstrated that MCPIP1 overexpression dramatically suppressed cell cycle progression and proliferation of TNBC cells in vitro and repressed tumor growth in vivo. Mechanistically, MCPIP1 was first demonstrated to act as a splicing factor to regulate AS in TNBC cells. Furthermore, we demonstrated that MCPIP1 modulated NFIC AS to promote CTF5 synthesis, which acted as a negative regulator in TNBC cells. Subsequently, we showed that CTF5 participated in MCPIP1-mediated antiproliferative effect by transcriptionally repressing cyclin D1 expression, as well as downregulating its downstream signaling targets p-Rb and E2F1. Conclusively, our findings provided novel insights into the anti-oncogenic mechanism of MCPIP1, suggesting that MCPIP1 could serve as an alternative treatment target in TNBC.
Lgals3bp suppresses colon inflammation and tumorigenesis through the downregulation of TAK1-NF-κB signaling
Authors: Cho Sang-Hee , Shim Hyun-Jeong , Park Mi-Ra , Choi Ji-Na , Akanda Md Rashedunnabi , Hwang Jun-Eul , Bae Woo-Kyun , Lee Kyung-Hwa , Sun Eun-Gene , Chung Ik-Joo 
Published: April 2021

AbstractGalectin 3-binding protein (LGALS3BP, also known as 90K) is a multifunctional glycoprotein involved in immunity and cancer. However, its precise role in colon inflammation and tumorigenesis remains unclear. Here, we showed that Lgals3bp−/− mice were highly susceptible to colitis and colon tumorigenesis, accompanied by the induction of inflammatory responses. In acute colitis, NF-κB was highly activated in the colon of Lgals3bp−/− mice, leading to the excessive production of pro-inflammatory cytokines, such as IL-6, TNFα, and IL-1β. Mechanistically, Lgals3bp suppressed NF-κB through the downregulation of TAK1 in colon epithelial cells. There was no significant difference in the pro-inflammatory cytokine levels between wild-type and Lgals3bp−/− mice in a chronic inflammatory state, during colon tumorigenesis. Instead, Lgals3bp−/− mice showed elevated levels of GM-CSF, compared to those in WT mice. We also found that GM-CSF promoted the accumulation of myeloid-derived suppressor cells and ultimately increased colon tumorigenesis in Lgals3bp−/− mice. Taken together, Lgals3bp plays a critical role in the suppression of colitis and colon tumorigenesis through the downregulation of the TAK1-NF-κB-cytokine axis. These findings suggest that LGALS3BP is a novel immunotherapeutic target for colon inflammation and tumorigenesis.