bluuebunny/crossref_metadata_2025_split huggingface dataset:
Motivational dispositions predict qualitative differences in oral task performance
Authors: Papi Mostafa , Eom Mijin , Zhang Yiran , Zhou Yang , Whiteside Zachary 
Published: May 2023

AbstractThe study examined how learners’ motivational dispositions predict the complexity, accuracy, fluency of their oral task performance and their overall second language proficiency. Eighty-one speakers of English as a second language in the United States completed a regulatory focus and a regulatory mode questionnaire, an oral interview task, and a picture description task. Regression analyses showed a meaningful pattern of results. The assessment mode (concerned with analysis, evaluation, and comparison) contributed to syntactic and lexical complexity, the reduction of dysfluencies, and overall English proficiency, whereas the locomotion mode (concerned with acting without deliberation) positively predicted the speed measure of fluency and the total number of errors. The prevention focus (concerned with stability, security, and safety) negatively predicted lexical sophistication, whereas the promotion focus (concerned with advancement, accomplishments, and growth) predicted overall English proficiency. Theoretical and instructional implications were discussed.
Land Control, Coal Resource Exploitation and Democratic Decline in Indonesia
Authors: Anugrah Iqra 
Published: May 2023

AbstractDebates on the causes of Indonesia's recent democratic decline have mostly focused on institutional, political and attitudinal–behavioural causes. By bringing the rural political economy dimension into this conversation, this article presents another picture of the illiberal turn in Indonesian democracy. Specifically, it examines the implications of elite control over land and coal resources on democratic quality. Based on in-country fieldwork materials and relevant secondary data, it analyses instances of episodic repression, the contraction of democratic spaces and the corrosive effects of coal-fuelled intra-elite clientelism by looking at the elite control of land resources and the influence of political and economic elites benefitting from the coal industry in elections and the broader political arena. Finally, it also discusses the capitulation of key agrarian social movement actors to state interests and its impact on the movement's ability to resist democratic regression. This elaboration shows how the current contour of elite control over rural resources contributes to the declining quality of Indonesian democracy.
On the Role of Macrophysics and Microphysics in Km‐Scale Simulations of Mixed‐Phase Clouds During Cold Air Outbreaks
Authors: Van Weverberg K. , Giangrande S. , Zhang D. , Morcrette C. J. , Field P. R. 
Published: May 2023

AbstractRegional atmospheric models struggle to maintain supercooled liquid in mixed‐phase clouds during polar cold‐air outbreaks (CAOs). Previous studies focused on the parameterization of aerosol, microphysics and turbulence to understand the origin of this widespread model bias. This study investigates the role of macrophysics parameterizations (MacP) in the simulation of mixed‐phase clouds. Km‐scale simulations are performed for a large number of CAO cases over Norway, for which continuous ground observations were collected at one site over 6 months. We use a novel analysis that attributes the cloud‐radiative errors to deficiencies in specific cloud regimes. We show that the MacP matters for cloud‐radiative effects in CAOs, but that it is probably not the primary cause of the lack of liquid water in simulated mixed‐phase clouds. Of all the MacP sensitivities explored in this study, the prognostic representation of both liquid and ice shows most promise in increasing the liquid water path. A newly proposed hybrid MacP with prognostic frozen and diagnostic liquid cloud fraction reproduces some of the benefits of the prognostic scheme at reduced cost and complexity. The two‐moment microphysics scheme in this study produces too large precipitation particles. Reducing the snow deposition rate decreases the precipitation particle sizes and largely improves the liquid water path. Simulations are less sensitive to reduced riming rates.
Volcanic Drivers of Stratospheric Sulfur in GFDL ESM4
Authors: Gao Chloe Yuchao , Naik Vaishali , Horowitz Larry W. , Ginoux Paul , Paulot Fabien , Dunne John , Mills Michael , Aquila Valentina , Colarco Peter 
Published: May 2023

AbstractStratospheric injections of sulfur dioxide from major volcanic eruptions perturb the Earth's global radiative balance and dominate variability in stratospheric sulfur loading. The atmospheric component of the GFDL Earth System Model (ESM4.1) uses a bulk aerosol scheme and previously prescribed the distribution of aerosol optical properties in the stratosphere. To quantify volcanic contributions to the stratospheric sulfur cycle and the resulting climate impact, we modified ESM4.1 to simulate stratospheric sulfate aerosols prognostically. Driven by explicit volcanic emissions of aerosol precursors and non‐volcanic sources, we conduct ESM4.1 simulations from 1989 to 2014, with a focus on the Mt. Pinatubo eruption. We evaluate our interactive representation of the stratospheric sulfur cycle against data from Moderate Resolution Imaging Spectroradiometer, Multi‐angle Imaging SpectroRadiometer, Advanced Very High Resolution Radiometer, High Resolution Infrared Radiation Sounder, and Stratospheric Aerosol and Gas Experiment II. To assess the key processes associated with volcanic aerosols, we performed a sensitivity analysis of sulfate burden from the Mt. Pinatubo eruption by varying injection heights, emission amount, and stratospheric sulfate's dry effective radius. We find that the simulated stratospheric sulfate mass burden and aerosol optical depth in the model are sensitive to these parameters, especially volcanic SO2 injection height, and the optimal combination of parameters depends on the metric we evaluate.
Holocene Water Balance Variations in Great Salt Lake, Utah: Application of GDGT Indices and the ACE Salinity Proxy
Authors: So Rachel T. , Lowenstein Tim K. , Jagniecki Elliot , Tierney Jessica E. , Feakins Sarah J. 
Published: May 2023

AbstractGreat Salt Lake (GSL), Utah, is a hypersaline terminal lake in the Great Basin, and the remnant of the late glacial Lake Bonneville. Holocene hydroclimate variations cannot be interpreted from the shoreline record, but instead can be investigated by proxies archived in the sediments. GLAD1‐GSL00‐1B was cored in 2000 and recently dated by radiocarbon for the Holocene section with the top 11 m representing ∼7 ka to present. Sediment samples every 30 cm (∼220 years) were studied for the full suite of microbial membrane lipids, including those responsive to temperature and salinity. The Archaeol and Caldarchaeol Ecometric (ACE) index detects the increase in lipids of halophilic archaea, relative to generalists, as salinity increases. We find Holocene ACE values ranged from 81 to 98, which suggests persistent hypersalinity with <50 g/L variability across 7.2 ka. The temperature proxy, MBTʹ5Me, yields values similar to modern mean annual air temperature for months above freezing (MAF = 15.7°C) over the last 5.5 ka. Several glycerol dialkyl glycerol tetraether metrics show a step shift in microbial communities and limnology at 5.5 ka. Extended archaeol detects elevated salinity during the regional mid‐Holocene drought, not readily detected in the ACE record that is often near the upper limit of the index. We infer that the mid‐Holocene GSL was shallower and saltier than the late Holocene. The current drying may be returning the lake to conditions not seen since the mid‐Holocene.
Seismic Evidence for Metamorphic Densification of the Lower Continental Crust in Eastern North America
Authors: Li Cong , Hibbard Leon , Gao Haiying , Williams Michael L. 
Published: May 2023

AbstractThe composition of the lower continental crust, as well as its formation, growth, and evolution, remains a fundamental subject to be understood. In this study, we carry out a comparative and integrative analysis of seismic tomographic models, teleseismic receiver function results, and Airy isostasy in order to investigate the properties of the lower continental crust in eastern North America. We extract the depths for Vs of 4.0 km/s, 4.2 km/s, and 4.5 km/s from three selected tomographic models and calculate the differences between the Vs depth contours and the Moho depth defined by receiver functions. We then calculate the Airy isostatic Moho depth and its misfit with the receiver‐function‐defined Moho. Our analysis reveals three key features: (a) the deepening of the Vs depth contours and the strong negative Airy misfit within the U.S. Grenville Province; (b) a seismically faster‐than‐average and compositionally denser‐than‐average lowermost crust in the eastern North American Craton and the Grenville Province; and (c) the thickest, seismically fastest, and densest lowermost crust beneath the southern Grenville Front, the southern Grenville‐Appalachian boundary, and the U.S.‐Canada national border. We suggest that the lower crust of the craton and the Grenville Province has densified through garnet‐forming metamorphic reactions during and after orogenesis, contributing to the widely distributed fast‐velocity layer. The lower crust beneath the tectonic boundaries could have experienced more extensive garnet growth during orogenesis and emplacement of mafic magma. This study provides new constraints on the seismic and compositional properties of the lower crust in eastern North America.
Distribution and survival strategies of endemic and cosmopolitan diazotrophs in the Arctic Ocean
Authors: Shiozaki Takuhei , Nishimura Yosuke , Yoshizawa Susumu , Takami Hideto , Hamasaki Koji , Fujiwara Amane , Nishino Shigeto , Harada Naomi 
Published: May 2023

Abstract
Dinitrogen (N2) fixation is the major source of reactive nitrogen in the ocean and has been considered to occur specifically in low-latitude oligotrophic oceans. Recent studies have shown that N2 fixation also occurs in the polar regions and thus is a global process, although the physiological and ecological characteristics of polar diazotrophs are not yet known. Here, we successfully reconstructed diazotroph genomes, including that of cyanobacterium UCYN-A (Candidatus ‘Atelocyanobacterium thalassa’), from metagenome data corresponding to 111 samples isolated from the Arctic Ocean. These diazotrophs were highly abundant in the Arctic Ocean (max., 1.28% of the total microbial community), suggesting that they have important roles in the Arctic ecosystem and biogeochemical cycles. Further, we show that diazotrophs within genera Arcobacter, Psychromonas, and Oceanobacter are prevalent in the &lt;0.2 µm fraction in the Arctic Ocean, indicating that current methods cannot capture their N2 fixation. Diazotrophs in the Arctic Ocean were either Arctic-endemic or cosmopolitan species from their global distribution patterns. Arctic-endemic diazotrophs, including Arctic UCYN-A, were similar to low-latitude-endemic and cosmopolitan diazotrophs in genome-wide function, however, they had unique gene sets (e.g., diverse aromatics degradation genes), suggesting adaptations to Arctic-specific conditions. Cosmopolitan diazotrophs were generally non-cyanobacteria and commonly had the gene that encodes the cold-inducible RNA chaperone, which presumably makes their survival possible even in deep, cold waters of global ocean and polar surface waters. This study shows global distribution pattern of diazotrophs with their genomes and provides clues to answering the question of how diazotrophs can inhabit polar waters.
Curcumin activates a ROS/KEAP1/NRF2/miR-34a/b/c cascade to suppress colorectal cancer metastasis
Authors: Liu Chunfeng , Rokavec Matjaz , Huang Zekai , Hermeking Heiko 
Published: May 2023

AbstractCurcumin, a natural phytochemical isolated from tumeric roots, represents a candidate for prevention and therapy of colorectal cancer/CRC. However, the exact mechanism of action and the downstream mediators of curcumin’s tumor suppressive effects have remained largely unknown. Here we used a genetic approach to determine the role of the p53/miR-34 pathway as mediator of the effects of curcumin. Three isogenic CRC cell lines rendered deficient for the p53, miR-34a and/or miR-34b/c genes were exposed to curcumin and subjected to cell biological analyses. siRNA-mediated inhibition and ectopic expression of NRF2, as well as Western blot, qPCR and qChIP analyses of its target genes were performed. CRC cells were i.v. injected into NOD/SCID mice and lung-metastases formation was determined by longitudinal, non-invasive imaging. In CRC cells curcumin induced apoptosis and senescence, and suppressed migration and invasion in a p53-independent manner. Curcumin activated the KEAP1/NRF2/ARE pathway by inducing ROS. Notably, curcumin induced miR-34a and miR-34b/c expression in a ROS/NRF2-dependent and p53-independent manner. NRF2 directly induced miR-34a and miR-34b/c via occupying multiple ARE motifs in their promoter regions. Curcumin reverted repression of miR-34a and miR-34b/c induced by IL6 and hypoxia. Deletion of miR-34a and miR-34b/c significantly reduced curcumin-induced apoptosis and senescence, and prevented the inhibition of migration and invasion by curcumin or ectopic NRF2. In CRC cells curcumin induced MET and prevented the formation of lung-metastases in mice in a miR-34a-dependent manner. In addition, we found that curcumin may enhance the therapeutic effects of 5-FU on CRC cells deficient for p53 and miR-34a/b/c. Activation of the KEAP1/NRF2/miR-34a/b/c axis mediates the tumor suppressive activity of curcumin and suggests a new approach for activating miR-34 genes in tumors for therapeutic purposes.
CD317 maintains proteostasis and cell survival in response to proteasome inhibitors by targeting calnexin for RACK1-mediated autophagic degradation
Authors: Cheng Jian , Zhang Guizhong , Deng Tian , Liu Zhao , Zhang Mengqi , Zhang Pengchao , Adeshakin Funmilayo O. , Niu Xiangyun , Yan Dehong , Wan Xiaochun , Yu Guang 
Published: May 2023

AbstractUnbalanced protein homeostasis (proteostasis) networks are frequently linked to tumorigenesis, making cancer cells more susceptible to treatments that target proteostasis regulators. Proteasome inhibition is the first licensed proteostasis-targeting therapeutic strategy, and has been proven effective in hematological malignancy patients. However, drug resistance almost inevitably develops, pressing for a better understanding of the mechanisms that preserve proteostasis in tumor cells. Here we report that CD317, a tumor-targeting antigen with a unique topology, was upregulated in hematological malignancies and preserved proteostasis and cell viability in response to proteasome inhibitors (PIs). Knocking down CD317 lowered Ca2+ levels in the endoplasmic reticulum (ER), promoting PIs-induced proteostasis failure and cell death. Mechanistically, CD317 interacted with calnexin (CNX), an ER chaperone protein that limits calcium refilling via the Ca2+ pump SERCA, thereby subjecting CNX to RACK1-mediated autophagic degradation. As a result, CD317 decreased the level of CNX protein, coordinating Ca2+ uptake and thus favoring protein folding and quality control in the ER lumen. Our findings reveal a previously unrecognized role of CD317 in proteostasis control and imply that CD317 could be a promising target for resolving PIs resistance in the clinic.
Genomic instability in individuals with sex determination defects and germ cell cancer
Authors: Krivega Maria , Zimmer Jutta , Slezko Anna , Frank-Herrmann Petra , Rehnitz Julia , Hohenfellner Markus , Bettendorf Markus , Luzarowski Marcin , Strowitzki Thomas 
Published: May 2023

AbstractThe ability to transmit genetic information through generations depends on the preservation of genome integrity. Genetic abnormalities affect cell differentiation, causing tissue specification defects and cancer. We addressed genomic instability in individuals with Differences of Sex Development (DSD), characterized by gonadal dysgenesis, infertility, high susceptibility for different types of cancer, especially Germ Cell Tumors (GCT), and in men with testicular GCTs. Whole proteome analysis of leukocytes, supported by specific gene expression assessment, and dysgenic gonads characterization, uncovered DNA damage phenotypes with altered innate immune response and autophagy. Further examination of DNA damage response revealed a reliance on deltaTP53, which was compromised by mutations in the transactivation domain in DSD-individuals with GCT. Accordingly, drug-induced rescue of DNA damage was achieved by autophagy inhibition but not by stabilization of TP53 in DSD-individuals’ blood in vitro. This study elucidates possibilities for prophylactic treatments of DSD-individuals, as well as new diagnostic approaches of GCT.
Designed active-site library reveals thousands of functional GFP variants
Authors: Weinstein Jonathan Yaacov , Martí-Gómez Carlos , Lipsh-Sokolik Rosalie , Hoch Shlomo Yakir , Liebermann Demian , Nevo Reinat , Weissman Haim , Petrovich-Kopitman Ekaterina , Margulies David , Ivankov Dmitry , McCandlish David M. , Fleishman Sarel J. 
Published: May 2023

AbstractMutations in a protein active site can lead to dramatic and useful changes in protein activity. The active site, however, is sensitive to mutations due to a high density of molecular interactions, substantially reducing the likelihood of obtaining functional multipoint mutants. We introduce an atomistic and machine-learning-based approach, called high-throughput Functional Libraries (htFuncLib), that designs a sequence space in which mutations form low-energy combinations that mitigate the risk of incompatible interactions. We apply htFuncLib to the GFP chromophore-binding pocket, and, using fluorescence readout, recover >16,000 unique designs encoding as many as eight active-site mutations. Many designs exhibit substantial and useful diversity in functional thermostability (up to 96 °C), fluorescence lifetime, and quantum yield. By eliminating incompatible active-site mutations, htFuncLib generates a large diversity of functional sequences. We envision that htFuncLib will be used in one-shot optimization of activity in enzymes, binders, and other proteins.
In-memory photonic dot-product engine with electrically programmable weight banks
Authors: Zhou Wen , Dong Bowei , Farmakidis Nikolaos , Li Xuan , Youngblood Nathan , Huang Kairan , He Yuhan , David Wright C. , Pernice Wolfram H. P. , Bhaskaran Harish 
Published: May 2023

AbstractElectronically reprogrammable photonic circuits based on phase-change chalcogenides present an avenue to resolve the von-Neumann bottleneck; however, implementation of such hybrid photonic–electronic processing has not achieved computational success. Here, we achieve this milestone by demonstrating an in-memory photonic–electronic dot-product engine, one that decouples electronic programming of phase-change materials (PCMs) and photonic computation. Specifically, we develop non-volatile electronically reprogrammable PCM memory cells with a record-high 4-bit weight encoding, the lowest energy consumption per unit modulation depth (1.7 nJ/dB) for Erase operation (crystallization), and a high switching contrast (158.5%) using non-resonant silicon-on-insulator waveguide microheater devices. This enables us to perform parallel multiplications for image processing with a superior contrast-to-noise ratio (≥87.36) that leads to an enhanced computing accuracy (standard deviation σ ≤ 0.007). An in-memory hybrid computing system is developed in hardware for convolutional processing for recognizing images from the MNIST database with inferencing accuracies of 86% and 87%.
Engineered symbiotic bacteria interfering Nosema redox system inhibit microsporidia parasitism in honeybees
Authors: Lang Haoyu , Wang Hao , Wang Haoqing , Zhong Zhaopeng , Xie Xianbing , Zhang Wenhao , Guo Jun , Meng Liang , Hu Xiaosong , Zhang Xue , Zheng Hao 
Published: May 2023

AbstractNosema ceranae is an intracellular parasite invading the midgut of honeybees, which causes serious nosemosis implicated in honeybee colony losses worldwide. The core gut microbiota is involved in protecting against parasitism, and the genetically engineering of the native gut symbionts provides a novel and efficient way to fight pathogens. Here, using laboratory-generated bees mono-associated with gut members, we find that Snodgrassella alvi inhibit microsporidia proliferation, potentially via the stimulation of host oxidant-mediated immune response. Accordingly, N. ceranae employs the thioredoxin and glutathione systems to defend against oxidative stress and maintain a balanced redox equilibrium, which is essential for the infection process. We knock down the gene expression using nanoparticle-mediated RNA interference, which targets the γ-glutamyl-cysteine synthetase and thioredoxin reductase genes of microsporidia. It significantly reduces the spore load, confirming the importance of the antioxidant mechanism for the intracellular invasion of the N. ceranae parasite. Finally, we genetically modify the symbiotic S. alvi to deliver dsRNA corresponding to the genes involved in the redox system of the microsporidia. The engineered S. alvi induces RNA interference and represses parasite gene expression, thereby inhibits the parasitism significantly. Specifically, N. ceranae is most suppressed by the recombinant strain corresponding to the glutathione synthetase or by a mixture of bacteria expressing variable dsRNA. Our findings extend our previous understanding of the protection of gut symbionts against N. ceranae and provide a symbiont-mediated RNAi system for inhibiting microsporidia infection in honeybees.
Dynamic BH3 profiling identifies pro-apoptotic drug combinations for the treatment of malignant pleural mesothelioma
Authors: Potter Danielle S. , Du Ruochen , Bohl Stephan R. , Chow Kin-Hoe , Ligon Keith L. , Bueno Raphael , Letai Anthony 
Published: May 2023

AbstractMalignant pleural mesothelioma (MPM) has relatively ineffective first/second-line therapy for advanced disease and only 18% five-year survival for early disease. Drug-induced mitochondrial priming measured by dynamic BH3 profiling identifies efficacious drugs in multiple disease settings. We use high throughput dynamic BH3 profiling (HTDBP) to identify drug combinations that prime primary MPM cells derived from patient tumors, which also prime patient derived xenograft (PDX) models. A navitoclax (BCL-xL/BCL-2/BCL-w antagonist) and AZD8055 (mTORC1/2 inhibitor) combination demonstrates efficacy in vivo in an MPM PDX model, validating HTDBP as an approach to identify efficacious drug combinations. Mechanistic investigation reveals AZD8055 treatment decreases MCL-1 protein levels, increases BIM protein levels, and increases MPM mitochondrial dependence on BCL-xL, which is exploited by navitoclax. Navitoclax treatment increases dependency on MCL-1 and increases BIM protein levels. These findings demonstrate that HTDBP can be used as a functional precision medicine tool to rationally construct combination drug regimens in MPM and other cancers.