bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of High‐Frequency Flow Variability on the Pathways of the Indonesian Throughflow
Authors: Iskandar Mochamad Riza , Jia Yanli , Sasaki Hideharu , Furue Ryo , Kida Shinichiro , Suga Toshio , Richards Kelvin J. 
Published: May 2023

AbstractPrevious studies have shown the presence of strong mesoscale eddy activities in the Indonesian Seas and their influence on the transport and water mass properties of the Indonesian Throughflow (ITF), a mean flow from the Pacific Ocean to the Indian Ocean through the Indonesian Archipelago. This study explores the effects of these eddy activities, or high‐frequency flow variability (HFFV), on residence time and pathway of the ITF by conducting Lagrangian particle tracking experiments using a velocity field from an eddy‐resolving ocean general circulation model. Particles are released at key locations in the western and eastern routes of the ITF and tracked both backward and forward in time. To assess the effects of flow variability that has a time scale longer than a day but shorter than a month, the definition of HFFV in this study, we conduct parallel experiments using daily and monthly averaged velocity fields. Particle trajectories reveal the contrasting circulation characteristics of the Sulawesi and Banda Seas. HFFV in the Sulawesi Sea (in the western route) is high, causing water to circulate longer over a broader area. The longer residence time in the Sulawesi Sea helps the upwelling of the inflowing Pacific waters, especially the intermediate water masses, to rise above 300 m at the Makassar Strait, and also has the potential to allow mixing processes to modify the water mass properties of the ITF. In contrast, HFFV is much lower in the Banda Sea and has minimal effects on the ITF.
Probabilistic Assessment of Antarctic Thermomechanical Structure: Impacts on Ice Sheet Stability
Authors: Hazzard James A. N. , Richards Fred D. , Goes Saskia D. B. , Roberts Gareth G. 
Published: May 2023

AbstractUncertainty in present‐day glacial isostatic adjustment (GIA) rates represents at least 44% of the total gravity‐based ice mass balance signal over Antarctica. Meanwhile, physical couplings between solid Earth, sea level and ice dynamics enhance the dependency of the spatiotemporally varying GIA signal on three‐dimensional variations in mantle rheology. Improved knowledge of thermomechanical mantle structure is therefore required to refine estimates of current and projected ice mass balance. Here, we present a Bayesian inverse method for self‐consistently mapping shear‐wave velocities from high‐resolution adjoint tomography into thermomechanical structure using calibrated parameterisations of anelasticity at seismic frequency. We constrain the model using regional geophysical data sets containing information on upper mantle temperature, attenuation and viscosity structure. Our treatment allows formal quantification of parameter covariances, and naturally permits propagation of material parameter uncertainties into thermomechanical structure estimates. We find that uncertainty in steady‐state viscosity structure at 150 km depth can be reduced by 4–5 orders of magnitude compared with a forward‐modeling approach neglecting covariance between viscoelastic parameters. By accounting for the dependence of apparent viscosity on loading timescale, we find good agreement between our estimates of mantle viscosity beneath West Antarctica, and those derived from satellite GPS. Direct access to temperature structure allows us to estimate lateral variations in lithosphere‐asthenosphere boundary (LAB) depth, geothermal heat flow (GHF), and associated uncertainties. We find evidence for shallow LAB depths (63 ± 13 km), and high GHF (76 ± 7 mW m−2) beneath West Antarctica that, combined with low asthenospheric viscosities, indicate a highly dynamic response to ice mass loss.
Vortioxetine hydrobromide inhibits the growth of gastric cancer cells in vivo and in vitro by targeting JAK2 and SRC
Authors: Li Mingzhu , Duan Lina , Wu Wenjie , Li Wenjing , Zhao Lili , Li Ang , Lu Xuebo , He Xinyu , Dong Zigang , Liu Kangdong , Jiang Yanan 
Published: May 2023

AbstractGastric cancer is the fourth leading cause of cancer deaths worldwide. Most patients are diagnosed in the advanced stage. Inadequate therapeutic strategies and the high recurrence rate lead to the poor 5-year survival rate. Therefore, effective chemopreventive drugs for gastric cancer are urgently needed. Repurposing clinical drugs is an effective strategy for discovering cancer chemopreventive drugs. In this study, we find that vortioxetine hydrobromide, an FDA-approved drug, is a dual JAK2/SRC inhibitor, and has inhibitory effects on cell proliferation of gastric cancer. Computational docking analysis, pull-down assay, cellular thermal shift assay (CETSA) and in vitro kinase assays are used to illustrate vortioxetine hydrobromide directly binds to JAK2 and SRC kinases and inhibits their kinase activities. The results of non-reducing SDS-PAGE and Western blotting indicate that vortioxetine hydrobromide suppresses STAT3 dimerization and nuclear translocation activity. Furthermore, vortioxetine hydrobromide inhibits the cell proliferation dependent on JAK2 and SRC and suppresses the growth of gastric cancer PDX model in vivo. These data demonstrate that vortioxetine hydrobromide, as a novel dual JAK2/SRC inhibitor, curbs the growth of gastric cancer in vitro and in vivo by JAK2/SRC-STAT3 signaling pathways. Our results highlight that vortioxetine hydrobromide has the potential application in the chemoprevention of gastric cancer.
Multi-trait genome-wide association analyses leveraging alcohol use disorder findings identify novel loci for smoking behaviors in the Million Veteran Program
Authors: Cheng Youshu , Dao Cecilia , Zhou Hang , Li Boyang , Kember Rachel L. , Toikumo Sylvanus , Zhao Hongyu , Gelernter Joel , Kranzler Henry R. , Justice Amy C. , Xu Ke 
Published: May 2023

AbstractSmoking behaviors and alcohol use disorder (AUD), both moderately heritable traits, commonly co-occur in the general population. Single-trait genome-wide association studies (GWAS) have identified multiple loci for smoking and AUD. However, GWASs that have aimed to identify loci contributing to co-occurring smoking and AUD have used small samples and thus have not been highly informative. Applying multi-trait analysis of GWASs (MTAG), we conducted a joint GWAS of smoking and AUD with data from the Million Veteran Program (N = 318,694). By leveraging GWAS summary statistics for AUD, MTAG identified 21 genome-wide significant (GWS) loci associated with smoking initiation and 17 loci associated with smoking cessation compared to 16 and 8 loci, respectively, identified by single-trait GWAS. The novel loci for smoking behaviors identified by MTAG included those previously associated with psychiatric or substance use traits. Colocalization analysis identified 10 loci shared by AUD and smoking status traits, all of which achieved GWS in MTAG, including variants onSIX3, NCAM1, and nearDRD2. Functional annotation of the MTAG variants highlighted biologically important regions onZBTB20, DRD2, PPP6C, andGCKRthat contribute to smoking behaviors. In contrast, MTAG of smoking behaviors and alcohol consumption (AC) did not enhance discovery compared with single-trait GWAS for smoking behaviors. We conclude that using MTAG to augment the power of GWAS enables the identification of novel genetic variants for commonly co-occuring phenotypes, providing new insights into their pleiotropic effects on smoking behavior and AUD.
Survival improvement of patients with FLT3 mutated acute myeloid leukemia: results from a prospective 9 years cohort
Authors: Oñate Guadalupe , Pratcorona Marta , Garrido Ana , Artigas-Baleri Alicia , Bataller Alex , Tormo Mar , Arnan Montserrat , Vives Susana , Coll Rosa , Salamero Olga , Vall-Llovera Ferran , Sampol Antònia , Garcia Antoni , Cervera Marta , Avila Sara Garcia , Bargay Joan , Ortín Xavier , Nomdedéu Josep F. , Esteve Jordi , Sierra Jorge ,   Spanish Cooperative Group for the Study and Treatment of Acute Leukemias and Myelodysplasias (CETLAM)
Published: May 2023

AbstractMidostaurin added to intensive chemotherapy is the standard of care for acute myeloid leukemia (AML) with FLT3 mutations (FLT3mut). We analyzed the impact of midostaurin in 227 FLT3mut-AML patients included in the AML-12 prospective trial for fit patients ≤70 years (#NCT04687098). Patients were divided into an early (2012–2015) and late (2016–2020) cohorts. They were uniformly treated except for the addition of midostaurin in 71% of late group patients. No differences were observed in response rates or the number of allotransplants between groups. Outcome was improved in the late period: 2-year relapse incidence decreased from 42% vs 29% in early vs late group (p = 0.024) and 2-year overall survival (OS) improved from 47% vs 61% (p = 0.042), respectively. The effect of midostaurin was evident in NPM1mut patients (n = 151), with 2-yr OS of 72% (exposed) vs 50% (naive) patients (p = 0.011) and mitigated FLT3-ITD allelic ratio prognostic value: 2-yr OS with midostaurin was 85% and 58% in low and high ratio patients (p = 0.049) vs 67% and 39% in naive patients (p = 0.005). In the wild-type NPM1 subset (n = 75), we did not observe significant differences between both study periods. In conclusion, this study highlights the improved outcome of FLT3mut AML fit patients with the incorporation of midostaurin.
Clarifying the effect of biodiversity on productivity in natural ecosystems with longitudinal data and methods for causal inference
Authors: Dee Laura E. , Ferraro Paul J. , Severen Christopher N. , Kimmel Kaitlin A. , Borer Elizabeth T. , Byrnes Jarrett E. K. , Clark Adam Thomas , Hautier Yann , Hector Andrew , Raynaud Xavier , Reich Peter B. , Wright Alexandra J. , Arnillas Carlos A. , Davies Kendi F. , MacDougall Andrew , Mori Akira S. , Smith Melinda D. , Adler Peter B. , Bakker Jonathan D. , Brauman Kate A. , Cowles Jane , Komatsu Kimberly , Knops Johannes M. H. , McCulley Rebecca L. , Moore Joslin L. , Morgan John W. , Ohlert Timothy , Power Sally A. , Sullivan Lauren L. , Stevens Carly , Loreau Michel 
Published: May 2023

AbstractCausal effects of biodiversity on ecosystem functions can be estimated using experimental or observational designs — designs that pose a tradeoff between drawing credible causal inferences from correlations and drawing generalizable inferences. Here, we develop a design that reduces this tradeoff and revisits the question of how plant species diversity affects productivity. Our design leverages longitudinal data from 43 grasslands in 11 countries and approaches borrowed from fields outside of ecology to draw causal inferences from observational data. Contrary to many prior studies, we estimate that increases in plot-level species richness caused productivity to decline: a 10% increase in richness decreased productivity by 2.4%, 95% CI [−4.1, −0.74]. This contradiction stems from two sources. First, prior observational studies incompletely control for confounding factors. Second, most experiments plant fewer rare and non-native species than exist in nature. Although increases in native, dominant species increased productivity, increases in rare and non-native species decreased productivity, making the average effect negative in our study. By reducing the tradeoff between experimental and observational designs, our study demonstrates how observational studies can complement prior ecological experiments and inform future ones.
Neutrophil metabolomics in severe COVID-19 reveal GAPDH as a suppressor of neutrophil extracellular trap formation
Authors: Li Yafeng , Hook Jessica S. , Ding Qing , Xiao Xue , Chung Stephen S. , Mettlen Marcel , Xu Lin , Moreland Jessica G. , Agathocleous Michalis 
Published: May 2023

AbstractSevere COVID-19 is characterized by an increase in the number and changes in the function of innate immune cells including neutrophils. However, it is not known how the metabolome of immune cells changes in patients with COVID-19. To address these questions, we analyzed the metabolome of neutrophils from patients with severe or mild COVID-19 and healthy controls. We identified widespread dysregulation of neutrophil metabolism with disease progression including in amino acid, redox, and central carbon metabolism. Metabolic changes in neutrophils from patients with severe COVID-19 were consistent with reduced activity of the glycolytic enzyme GAPDH. Inhibition of GAPDH blocked glycolysis and promoted pentose phosphate pathway activity but blunted the neutrophil respiratory burst. Inhibition of GAPDH was sufficient to cause neutrophil extracellular trap (NET) formation which required neutrophil elastase activity. GAPDH inhibition increased neutrophil pH, and blocking this increase prevented cell death and NET formation. These findings indicate that neutrophils in severe COVID-19 have an aberrant metabolism which can contribute to their dysfunction. Our work also shows that NET formation, a pathogenic feature of many inflammatory diseases, is actively suppressed in neutrophils by a cell-intrinsic mechanism controlled by GAPDH.
Probing excitations and cooperatively rearranging regions in deeply supercooled liquids
Authors: Ortlieb Levke , Ingebrigtsen Trond S. , Hallett James E. , Turci Francesco , Royall C. Patrick 
Published: May 2023

AbstractUpon approaching the glass transition, the relaxation of supercooled liquids is controlled by activated processes, which become dominant at temperatures below the so-called dynamical crossover predicted by Mode Coupling theory (MCT). Two of the main frameworks rationalising this behaviour are dynamic facilitation theory (DF) and the thermodynamic scenario which give equally good descriptions of the available data. Only particle-resolved data from liquids supercooled below the MCT crossover can reveal the microscopic mechanism of relaxation. By employing state-of-the-art GPU simulations and nano-particle resolved colloidal experiments, we identify the elementary units of relaxation in deeply supercooled liquids. Focusing on the excitations of DF and cooperatively rearranging regions (CRRs) implied by the thermodynamic scenario, we find that several predictions of both hold well below the MCT crossover: for the elementary excitations, their density follows a Boltzmann law, and their timescales converge at low temperatures. For CRRs, the decrease in bulk configurational entropy is accompanied by the increase of their fractal dimension. While the timescale of excitations remains microscopic, that of CRRs tracks a timescale associated with dynamic heterogeneity, $${t}^{*} \sim {\tau }_{\alpha }^{0.8}$$

t

*

~

τ

α

0.8

. This timescale separation of excitations and CRRs opens the possibility of accumulation of excitations giving rise to cooperative behaviour leading to CRRs.
Paired immunoglobulin-like receptor B is an entry receptor for mammalian orthoreovirus
Authors: Shang Pengcheng , Simpson Joshua D. , Taylor Gwen M. , Sutherland Danica M. , Welsh Olivia L. , Aravamudhan Pavithra , Natividade Rita Dos Santos , Schwab Kristina , Michel Joshua J. , Poholek Amanda C. , Wu Yijen , Rajasundaram Dhivyaa , Koehler Melanie , Alsteens David , Dermody Terence S. 
Published: May 2023

AbstractMammalian orthoreovirus (reovirus) infects most mammals and is associated with celiac disease in humans. In mice, reovirus infects the intestine and disseminates systemically to cause serotype-specific patterns of disease in the brain. To identify receptors conferring reovirus serotype-dependent neuropathogenesis, we conducted a genome-wide CRISPRa screen and identified paired immunoglobulin-like receptor B (PirB) as a receptor candidate. Ectopic expression of PirB allowed reovirus binding and infection. PirB extracelluar D3D4 region is required for reovirus attachment and infectivity. Reovirus binds to PirB with nM affinity as determined by single molecule force spectroscopy. Efficient reovirus endocytosis requires PirB signaling motifs. In inoculated mice, PirB is required for maximal replication in the brain and full neuropathogenicity of neurotropic serotype 3 (T3) reovirus. In primary cortical neurons, PirB expression contributes to T3 reovirus infectivity. Thus, PirB is an entry receptor for reovirus and contributes to T3 reovirus replication and pathogenesis in the murine brain.
Analysis of PPI networks of transcriptomic expression identifies hub genes associated with Newcastle disease virus persistent infection in bladder cancer
Authors: Ahmad Umar , Abdullah Syahril , Chau De Ming , Chia Suet Lin , Yusoff Khatijah , Chan Soon Choy , Ong Teng Aik , Razack Azad Hassan , Veerakumarasivam Abhi 
Published: May 2023

AbstractBladder cancer cells can acquire persistent infection of oncolytic Newcastle disease virus (NDV) but the molecular mechanism(s) remain unelucidated. This poses a major barrier to the effective clinical translation of oncolytic NDV virotherapy of cancers. To improve our understanding of the molecular mechanism(s) associated with the development of NDV persistent infection in bladder cancer, we used mRNA expression profiles of persistently infected bladder cancer cells to construct PPI networks. Based on paths and modules in the PPI network, the bridges were found mainly in the upregulated mRNA-pathways of p53 signalling, ECM-receptor interaction, and TGF-beta signalling and downregulated mRNA-pathways of antigen processing and presentation, protein processing in endoplasmic reticulum, completement and coagulation cascades in persistent TCCSUPPi cells. In persistent EJ28Pi cells, connections were identified mainly through upregulated mRNA-pathways of renal carcinoma, viral carcinogenesis, Ras signalling and cell cycle and the downregulated mRNA-pathways of Wnt signalling, HTLV-I infection and pathways in cancers. These connections were mainly dependent on RPL8-HSPA1A/HSPA4 in TCCSUPPi cells and EP300, PTPN11, RAC1—TP53, SP1, CCND1 and XPO1 in EJ28Pi cells. Oncomine validation showed that the top hub genes identified in the networks that include RPL8, THBS1, F2 from TCCSUPPi and TP53 and RAC1 from EJ28Pi are involved in the development and progression of bladder cancer. Protein-drug interaction networks identified several putative drug targets that could be used to disrupt the linkages between the modules and prevent bladder cancer cells from acquiring NDV persistent infection. This novel PPI network analysis of differentially expressed mRNAs of NDV persistently infected bladder cancer cell lines provide an insight into the molecular mechanisms of NDV persistency of infection in bladder cancers and the future screening of drugs that can be used together with NDV to enhance its oncolytic efficacy.
E. coli allantoinase is activated by the downstream metabolic enzyme, glycerate kinase, and stabilizes the putative allantoin transporter by direct binding
Authors: Rodionova Irina A. , Hosseinnia Ali , Kim Sunyoung , Goodacre Norman , Zhang Li , Zhang Zhongge , Palsson Bernhard , Uetz Peter , Babu Mohan , Saier Milton H. 
Published: May 2023

AbstractAllantoin is a good source of ammonium for many organisms, and in Escherichia coli it is utilized under anaerobic conditions. We provide evidence that allantoinase (AllB) is allosterically activated by direct binding of the allantoin catabolic enzyme, glycerate 2-kinase (GlxK) in the presence of glyoxylate. Glyoxylate is known to be an effector of the AllR repressor which regulates the allantoin utilization operons in E. coli. AllB has low affinity for allantoin, but its activation by GlxK leads to increased affinity for its substrate. We also show that the predicted allantoin transporter YbbW (re-named AllW) has allantoin specificity and the protein–protein interaction with AllB. Our results show that the AllB-dependent allantoin degradative pathway is subject to previously unrecognized regulatory mechanisms involving direct protein–protein interactions.
Perceptions of intelligence & sentience shape children’s interactions with robot reading companions
Authors: Caruana Nathan , Moffat Ryssa , Miguel-Blanco Aitor , Cross Emily S. 
Published: May 2023

AbstractThe potential for robots to support education is being increasingly studied and rapidly realised. However, most research evaluating education robots has neglected to examine the fundamental features that make them more or less effective, given the needs and expectations of learners. This study explored how children’s perceptions, expectations and experiences are shaped by aesthetic and functional features during interactions with different robot ‘reading buddies’. We collected a range of quantitative and qualitative measures of subjective experience before and after children read a book with one of three different robots. An inductive thematic analysis revealed that robots have the potential offer children an engaging and non-judgemental social context to promote reading engagement. This was supported by children’s perceptions of robots as being intelligent enough to read, listen and comprehend the story, particularly when they had the capacity to talk. A key challenge in the use of robots for this purpose was the unpredictable nature of robot behaviour, which remains difficult to perfectly control and time using either human operators or autonomous algorithms. Consequently, some children found the robots’ responses distracting. We provide recommendations for future research seeking to position seemingly sentient and intelligent robots as an assistive tool within and beyond education settings.
Study on the mechanical properties of unloading damaged sandstone under cyclic loading and unloading
Authors: Zhang Hengbin , Wang Lehua , Li Jianlin , Deng Huafeng , Xu Xiaoliang 
Published: May 2023

AbstractTo reveal the mechanical properties of rocks under stress disturbance and unloading confining pressure, conventional triaxial compression tests, triaxial compression tests on unloading damaged sandstone, and cyclic loading and unloading tests on unloading damaged sandstone were conducted. Then, the evolutionary characteristics of dissipated energy in sandstone under cyclic loading and unloading were explored, and damage variables were proposed. The crack development characteristics were analyzed from a microscopic perspective. The study results reveal that: (1) the sandstone exhibits obvious brittle failure under different stress paths, and the macroscopic failure mode is dominated by shear failure. As the number of cycles increases, the load-bearing capacity, elastic modulus, and deformation modulus of the sandstone will be significantly reduced if it suffers greater unloading damage. (2) The cyclic action in the early stage inhibits the development of the internal fracture. However, the inhibitory effect is significantly reduced for specimens with larger unloading quantities. The damage variable in the cyclic loading and unloading is about 50.00% of that in the unloading, indicating that unloading confining pressure is the dominant factor for specimen failure. (3) The extension of microcracks within the sandstone is dominated by intergranular cracks, and the number of cracks increases with the increase of unloading quantity. After cyclic loading and unloading, the structure becomes looser. The test results deepen the understanding of rock mechanical behavior and fracture evolution under cyclic loading and can provide a basis for structural stability improvement under stress disturbance and unloading confining pressure.