bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deep Learning‐Based Rapid Flood Inundation Modeling for Flat Floodplains With Complex Flow Paths
Authors: Zhou Yuerong , Wu Wenyan , Nathan Rory , Wang Q. J. 
Published: December 2022

AbstractFlood inundation emulation models based on deep neural networks have been developed to overcome the computational burden of two‐dimensional (2D) hydrodynamic models. Challenges remain for flat and complex floodplains where many anabranches form during flood events. In this study, we propose a new approach to simulate the temporal and spatial variation of flood inundation for a floodplain with complex flow paths. A U‐Net‐based spatial reduction and reconstruction method (USRR) is used to find representative locations on the floodplain with complex flow paths. The water depths at these locations are simulated using one‐dimensional convolutional neural network (1D‐CNN) models, which are well‐suited to handling multivariate timeseries inputs. The flood surface is then reconstructed using the USRR method and the simulated flood depths at the representative locations. The combined 1D‐CNN and USRR method is compared with a previously developed approach based on the long short‐term memory recurrent neural network (LSTM) models and a 2D linear interpolation‐based SRR method. Compared to the LSTM model, the 1D‐CNN model is not only more accurate, but also takes less time to develop. Although both surface reconstruction methods take <1 s to produce an inundation map for a specific point in time, the USRR method is more accurate than the SRR method, leading to an increase of 5.6% in the proportion of correctly detected inundation area. The combination of 1D‐CNN and USRR can detect over 95% of the inundated area simulated using a 2D hydrodynamic model but is 98 times faster.
Analogous comparison unravels heightened antiviral defense and boosted viral infection upon immunosuppression in bat organoids
Authors: Liu Xiaojuan , Li Cun , Wan Zhixin , Chiu Man Chun , Huang Jingjing , Yu Yifei , Zhu Lin , Cai Jian-Piao , Rong Lei , Song You-qiang , Chu Hin , Cai Zongwei , Jiang Shibo , Yuen Kwok-yung , Zhou Jie 
Published: December 2022

AbstractHorseshoe bats host numerous SARS-related coronaviruses without overt disease signs. Bat intestinal organoids, a unique model of bat intestinal epithelium, allow direct comparison with human intestinal organoids. We sought to unravel the cellular mechanism(s) underlying bat tolerance of coronaviruses by comparing the innate immunity in bat and human organoids. We optimized the culture medium, which enabled a consecutive passage of bat intestinal organoids for over one year. Basal expression levels of IFNs and IFN-stimulated genes were higher in bat organoids than in their human counterparts. Notably, bat organoids mounted a more rapid, robust and prolonged antiviral defense than human organoids upon Poly(I:C) stimulation. TLR3 and RLR might be the conserved pathways mediating antiviral response in bat and human intestinal organoids. The susceptibility of bat organoids to a bat coronavirus CoV-HKU4, but resistance to EV-71, an enterovirus of exclusive human origin, indicated that bat organoids adequately recapitulated the authentic susceptibility of bats to certain viruses. Importantly, TLR3/RLR inhibition in bat organoids significantly boosted viral growth in the early phase after SARS-CoV-2 or CoV-HKU4 infection. Collectively, the higher basal expression of antiviral genes, especially more rapid and robust induction of innate immune response, empowered bat cells to curtail virus propagation in the early phase of infection.
Prognostic impact of the AML ELN2022 risk classification in patients undergoing allogeneic stem cell transplantation
Authors: Jentzsch Madlen , Bischof Lara , Ussmann Jule , Backhaus Donata , Brauer Dominic , Metzeler Klaus H. , Merz Maximilian , Vucinic Vladan , Franke Georg-Nikolaus , Herling Marco , Platzbecker Uwe , Schwind Sebastian 
Published: December 2022

AbstractFor most patients with acute myeloid leukemia (AML), an allogeneic hematopoietic stem cell transplantation (HSCT) offers the highest chance of cure. Recently, the European LeukemiaNet (ELN) published updated recommendations on the diagnosis and risk classification in AML based on genetic factors at diagnosis as well as a dynamic adjustment (reclassification) according to the measurable residual disease (MRD) status for the favorable and intermediate risk groups. Validation of the ELN2022 risk classification has not been reported. We retrospectively analyzed 522 AML patients who received an HSCT at a median age of 59 (range 16–76) years. For patients with adequate material available and in remission prior to HSCT (n = 229), the MRD status was evaluated. Median follow-up after HSCT was 3.0 years. ELN2022 risk at diagnosis was in 22% favorable, in 26% intermediate, and in 52% adverse. ELN2022 risk at diagnosis is associated with the cumulative incidence of relapse/progression (CIR), event-free survival (EFS), and overall survival (OS) in the whole patient cohort, as well as the subgroup of patients transplanted in first remission. However, the risk stratification based on the ELN2022 classification did not significantly improve outcome prognostication in comparison to the ELN2017 classification. In our study, the newly added group of patients with myelodysplasia-related gene mutations did not have adverse outcomes. Re-classifying these patients into the intermediate risk group and adjusting the grouping for all AML patients by MRD at HSCT, led to a refined and improved risk stratification, which should be validated in independent studies.
Glucocorticoid-induced microRNA-378 signaling mediates the progression of pancreatic cancer by enhancing autophagy
Authors: Liu Li , Han Shanshan , Xiao Xi , An Xuefeng , Gladkich Jury , Hinz Ulf , Hillmer Stefan , Hoppe-Tichy Torsten , Xu Yi , Schaefer Michael , Strobel Oliver , Herr Ingrid 
Published: December 2022

AbstractGlucocorticoids (GCs) are widely used in tumor therapy to reduce tumor growth, inflammation, edema, and other side effects. Controversially, GCs may also cause the progression of highly aggressive pancreatic ductal adenocarcinoma (PDAC). Because microRNA (miR) and autophagy signaling support the invasive growth of PDAC, we asked whether these mechanisms may be targeted by GCs. Six established human PDAC cell lines, tissue from patients who received GC medication (n = 35) prior to surgery, or not (n = 35), and tumor xenografts were examined by RT‒qPCR, transmission electron microscopy (TEM), monodansylcadaverine (MDC) staining, immunohistochemistry, in situ hybridization, gene array and Kaplan‒Meier analysis with bioinformatics, and MTT, western blot, colony, spheroid, migration, and invasion assays. We found that various GCs, including dexamethasone (DEX), induced typical features of macroautophagy with the appearance of autolysosomes, enhanced LC3-II, decreased SQSTM1/p62 expression and induced epithelial-mesenchymal transition (EMT) and gemcitabine resistance. The GC receptor (GR) antagonist mifepristone (RU486) counteracted DEX-induced autophagy features, suggesting that the GC-GR complex is involved in the induction of autophagy. The autophagy-related miR-378i and miR-378a-3p were selected as the top upregulated candidates, and their high expression in PDAC patient tissue correlated with low survival. siRNA-mediated downregulation of miR-378 inhibited DEX-induced autophagy, and tumor progression. Bioinformatics confirmed the contribution of miR-378 to the regulation of signaling networks involved in GC-induced autophagy and tumor progression. The construction of a molecular docking model revealed stable binding of miR-378 to the DEX-GR complex, suggesting direct regulation. These substantial, novel, in-depth data reveal that GCs favor autophagy-mediated cancer progression by inducing miR-378 and GR binding and implicate GR and miR-378 as new therapeutic targets.
Ultrasensitive rapid cytokine sensors based on asymmetric geometry two-dimensional MoS2 diodes
Authors: De Silva Thushani , Fawzy Mirette , Hasani Amirhossein , Ghanbari Hamidreza , Abnavi Amin , Askar Abdelrahman , Ling Yue , Mohammadzadeh Mohammad Reza , Kabir Fahmid , Ahmadi Ribwar , Rosin Miriam , Kavanagh Karen L. , Adachi Michael M. 
Published: December 2022

AbstractThe elevation of cytokine levels in body fluids has been associated with numerous health conditions. The detection of these cytokine biomarkers at low concentrations may help clinicians diagnose diseases at an early stage. Here, we report an asymmetric geometry MoS2 diode-based biosensor for rapid, label-free, highly sensitive, and specific detection of tumor necrosis factor-α (TNF-α), a proinflammatory cytokine. This sensor is functionalized with TNF-α binding aptamers to detect TNF-α at concentrations as low as 10 fM, well below the typical concentrations found in healthy blood. Interactions between aptamers and TNF-α at the sensor surface induce a change in surface energy that alters the current-voltage rectification behavior of the MoS2 diode, which can be read out using a two-electrode configuration. The key advantages of this diode sensor are the simple fabrication process and electrical readout, and therefore, the potential to be applied in a rapid and easy-to-use, point-of-care, diagnostic tool.
Rapid and reversible optogenetic silencing of synaptic transmission by clustering of synaptic vesicles
Authors: Vettkötter Dennis , Schneider Martin , Goulden Brady D. , Dill Holger , Liewald Jana , Zeiler Sandra , Guldan Julia , Ateş Yilmaz Arda , Watanabe Shigeki , Gottschalk Alexander 
Published: December 2022

AbstractAcutely silencing specific neurons informs about their functional roles in circuits and behavior. Existing optogenetic silencers include ion pumps, channels, metabotropic receptors, and tools that damage the neurotransmitter release machinery. While the former hyperpolarize the cell, alter ionic gradients or cellular biochemistry, the latter allow only slow recovery, requiring de novo synthesis. Thus, tools combining fast activation and reversibility are needed. Here, we use light-evoked homo-oligomerization of cryptochrome CRY2 to silence synaptic transmission, by clustering synaptic vesicles (SVs). We benchmark this tool, optoSynC, in Caenorhabditis elegans, zebrafish, and murine hippocampal neurons. optoSynC clusters SVs, observable by electron microscopy. Locomotion silencing occurs with tauon ~7.2 s and recovers with tauoff ~6.5 min after light-off. optoSynC can inhibit exocytosis for several hours, at very low light intensities, does not affect ion currents, biochemistry or synaptic proteins, and may further allow manipulating different SV pools and the transfer of SVs between them.
Rational enzyme design for enabling biocatalytic Baldwin cyclization and asymmetric synthesis of chiral heterocycles
Authors: Li Jun-Kuan , Qu Ge , Li Xu , Tian Yuchen , Cui Chengsen , Zhang Fa-Guang , Zhang Wuyuan , Ma Jun-An , Reetz Manfred T. , Sun Zhoutong 
Published: December 2022

AbstractChiral heterocyclic compounds are needed for important medicinal applications. We report an in silico strategy for the biocatalytic synthesis of chiral N- and O-heterocycles via Baldwin cyclization modes of hydroxy- and amino-substituted epoxides and oxetanes using the limonene epoxide hydrolase from Rhodococcus erythropolis. This enzyme normally catalyzes hydrolysis with formation of vicinal diols. Firstly, the required shutdown of the undesired natural water-mediated ring-opening is achieved by rational mutagenesis of the active site. In silico enzyme design is then continued with generation of the improved mutants. These variants prove to be versatile catalysts for preparing chiral N- and O-heterocycles with up to 99% conversion, and enantiomeric ratios up to 99:1. Crystal structural data and computational modeling reveal that Baldwin-type cyclizations, catalyzed by the reprogrammed enzyme, are enabled by reshaping the active-site environment that directs the distal RHN and HO-substituents to be intramolecular nucleophiles.
Number of simultaneously acting global change factors affects composition, diversity and productivity of grassland plant communities
Authors: Speißer Benedikt , Wilschut Rutger A. , van Kleunen Mark 
Published: December 2022

AbstractPlant communities experience impacts of increasing numbers of global change factors (e.g., warming, eutrophication, pollution). Consequently, unpredictable global change effects could arise. However, information about multi-factor effects on plant communities is scarce. To test plant-community responses to multiple global change factors (GCFs), we subjected sown and transplanted-seedling communities to increasing numbers (0, 1, 2, 4, 6) of co-acting GCFs, and assessed effects of individual factors and increasing numbers of GCFs on community composition and productivity. GCF number reduced species diversity and evenness of both community types, whereas none of the individual factors alone affected these measures. In contrast, GCF number positively affected the productivity of the transplanted-seedling community. Our findings show that simultaneously acting GCFs can affect plant communities in ways differing from those expected from single factor effects, which may be due to biological effects, sampling effects, or both. Consequently, exploring the multifactorial nature of global change is crucial to better understand ecological impacts of global change.
Bioenergetics of pollen tube growth in Arabidopsis thaliana revealed by ratiometric genetically encoded biosensors
Authors: Liu Jinhong , Lim Shey-Li , Zhong Jia Yi , Lim Boon Leong 
Published: December 2022

AbstractPollen tube is the fastest-growing plant cell. Its polarized growth process consumes a tremendous amount of energy, which involves coordinated energy fluxes between plastids, the cytosol, and mitochondria. However, how the pollen tube obtains energy and what the biological roles of pollen plastids are in this process remain obscure. To investigate this energy-demanding process, we developed second-generation ratiometric biosensors for pyridine nucleotides which are pH insensitive between pH 7.0 to pH 8.5. By monitoring dynamic changes in ATP and NADPH concentrations and the NADH/NAD+ ratio at the subcellular level in Arabidopsis (Arabidopsis thaliana) pollen tubes, we delineate the energy metabolism that underpins pollen tube growth and illustrate how pollen plastids obtain ATP, NADPH, NADH, and acetyl-CoA for fatty acid biosynthesis. We also show that fermentation and pyruvate dehydrogenase bypass are not essential for pollen tube growth in Arabidopsis, in contrast to other plant species like tobacco and lily.
Self-rolling of vanadium dioxide nanomembranes for enhanced multi-level solar modulation
Authors: Li Xing , Cao Cuicui , Liu Chang , He Wenhao , Wu Kaibo , Wang Yang , Xu Borui , Tian Ziao , Song Enming , Cui Jizhai , Huang Gaoshan , Zheng Changlin , Di Zengfeng , Cao Xun , Mei Yongfeng 
Published: December 2022

AbstractThermochromic window develops as a competitive solution for carbon emissions due to comprehensive advantages of its passivity and effective utilization of energy. How to further enhance the solar modulation ($${\triangle T}_{{{{{{{\rm{sol}}}}}}}}$$

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) of thermochromic windows while ensuring high luminous transmittance ($${T}_{{{{{{{\rm{lum}}}}}}}}$$

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) becomes the latest challenge to touch the limit of energy efficiency. Here, we show a smart window combining mechanochromism with thermochromism by self-rolling of vanadium dioxide (VO2) nanomembranes to enhance multi-level solar modulation. The mechanochromism is introduced by the temperature-controlled regulation of curvature of rolled-up smart window, which benefits from effective strain adjustment in VO2 nanomembranes upon the phase transition. Under geometry design and optimization, the rolled-up smart window with high $${\triangle T}_{{{{\rm{sol}}}}}$$

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and $${T}_{{{{{{\rm{lum}}}}}}}$$

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is achieved for the modulation of indoor temperature self-adapted to seasons and climate. Furthermore, such rolled-up smart window enables high infrared reflectance after triggered phase transition and acts as a smart lens protective cover for strong radiation. This work supports the feasibility of self-rolling technology in smart windows and lens protection, which promises broad interest and practical applications of self-adapting devices and systems for smart building, intelligent sensors and actuators with the perspective of energy efficiency.
Hedgehog-mediated gut-taste neuron axis controls sweet perception in Drosophila
Authors: Zhao Yunpo , Khallaf Mohammed A. , Johansson Emilia , Dzaki Najat , Bhat Shreelatha , Alfredsson Johannes , Duan Jianli , Hansson Bill S. , Knaden Markus , Alenius Mattias 
Published: December 2022

AbstractDietary composition affects food preference in animals. High sugar intake suppresses sweet sensation from insects to humans, but the molecular basis of this suppression is largely unknown. Here, we reveal that sugar intake in Drosophila induces the gut to express and secrete Hedgehog (Hh) into the circulation. We show that the midgut secreted Hh localize to taste sensilla and suppresses sweet sensation, perception, and preference. We further find that the midgut Hh inhibits Hh signalling in the sweet taste neurons. Our electrophysiology studies demonstrate that the midgut Hh signal also suppresses bitter taste and some odour responses, affecting overall food perception and preference. We further show that the level of sugar intake during a critical window early in life, sets the adult gut Hh expression and sugar perception. Our results together reveal a bottom-up feedback mechanism involving a “gut-taste neuron axis” that regulates food sensation and preference.
A robust pipeline for ranking carrier frequencies of autosomal recessive and X-linked Mendelian disorders
Authors: Zhu Wenjuan , Wang Chen , Mullapudi Nandita , Cao Yanan , Li Lin , Lo Ivan Fai Man , Tsui Stephen Kwok-Wing , Chen Xiao , Lei Yong , Gu Shen 
Published: December 2022

AbstractSingle gene disorders are individually rare but collectively common leading causes of neonatal and pediatric morbidity and mortality. Both parents or the mothers of affected individuals with autosomal recessive or X-linked recessive diseases, respectively, are carrier(s). Carrier frequencies of recessive diseases can vary drastically among different ethnicities. This study established a robust pipeline for estimating and ranking carrier frequencies of all known 2699 recessive genes based on genome-wide sequencing data in healthy individuals. The discovery gnomAD cohort contained sequencing data on 76,156 genomes and 125,748 exomes from individuals with seven ethnicity backgrounds. The three validation cohorts composed of the SG10K Project with 4810 genomes on East Asian and South Asian, the ChinaMAP project with 10,588 Chinese genomes, and the WBBC pilot project with 4480 Chinese genomes. Within each cohort, comprehensive selection criteria for various kinds of deleterious variants were instituted, including known pathogenic variants (Type 1), presumably loss-of-function changes (Type 2), predicted deleterious missense variants (Type 3), and potentially harmful in-frame INDELs (Type 4). Subsequently, carrier frequencies of the 2699 genes were calculated and ranked based on ethnicity-specific carrier rates of Type 1 to Type 4 variants. Comparison of results from different cohorts with similar ethnicity background exhibited high degree of correlation, particularly between the ChinaMAP and the WBBC cohorts (Pearson correlation coefficient R = 0.92), confirming the validity of our variant selection criteria and the overall analysis pipeline.
Measuring magic on a quantum processor
Authors: Oliviero Salvatore F. E. , Leone Lorenzo , Hamma Alioscia , Lloyd Seth 
Published: December 2022

AbstractMagic states are the resource that allows quantum computers to attain an advantage over classical computers. This resource consists in the deviation from a property called stabilizerness which in turn implies that stabilizer circuits can be efficiently simulated on a classical computer. Without magic, no quantum computer can do anything that a classical computer cannot do. Given the importance of magic for quantum computation, it would be useful to have a method for measuring the amount of magic in a quantum state. In this work, we propose and experimentally demonstrate a protocol for measuring magic based on randomized measurements. Our experiments are carried out on two IBM Quantum Falcon processors. This protocol can provide a characterization of the effectiveness of a quantum hardware in producing states that cannot be effectively simulated on a classical computer. We show how from these measurements one can construct realistic noise models affecting the hardware.
Effective vaccination strategy using SARS-CoV-2 spike cocktail against Omicron and other variants of concern
Authors: Shi Juan , Wang Gang , Zheng Jian , Verma Abhishek K. , Guan Xiaoqing , Malisheni Moffat M. , Geng Qibin , Li Fang , Perlman Stanley , Du Lanying 
Published: December 2022

AbstractThe SARS-CoV-2 Omicron variant harbors more than 30 mutations in its spike (S) protein. Circulating Omicron subvariants, particularly BA5 and other variants of concern (VOCs), show increased resistance to COVID-19 vaccines that target the original S protein, calling for an urgent need for effective vaccines to prevent multiple SARS-CoV-2 VOCs. Here, we evaluated the neutralizing activity and protection conferred by a BA1-S subunit vaccine when combined with or used as booster doses after, administration of wild-type S protein (WT-S). A WT-S/BA1-S cocktail, or WT-S prime and BA1-S boost, induced significantly higher neutralizing antibodies against pseudotyped Omicron BA1, BA2, BA2.12.1, and BA5 subvariants, and similar or higher neutralizing antibodies against the original SARS-CoV-2, than the WT-S protein alone. The WT-S/BA1-S cocktail also elicited higher or significantly higher neutralizing antibodies than the WT-S-prime-BA1-S boost, WT-S alone, or BA1-S alone against pseudotyped SARS-CoV-2 Alpha, Beta, Gamma, and Delta VOCs, and SARS-CoV, a closely related beta-coronavirus using the same receptor as SARS-CoV-2 for viral entry. By contrast, WT-S or BA1-S alone failed to induce potent neutralizing antibodies against all these viruses. Similar to the WT-S-prime-BA1-S boost, the WT-S/BA1-S cocktail completely protected mice against the lethal challenge of a Delta variant with negligible weight loss. Thus, we have identified an effective vaccination strategy that elicits potent, broadly, and durable neutralizing antibodies against circulating SARS-CoV-2 Omicron subvariants, other VOCs, original SARS-CoV-2, and SARS-CoV. These results will provide useful guidance for developing efficacious vaccines that inhibit current and future SARS-CoV-2 variants to control the COVID-19 pandemic.