bluuebunny/crossref_metadata_2025_split huggingface dataset:
Wind, Rain, and the Closed to Open Cell Transition in Subtropical Marine Stratocumulus
Authors: Eastman Ryan , McCoy Isabel L. , Wood Robert 
Published: September 2022

AbstractLagrangian transitions in mesoscale cellular convective (MCC) clouds beginning as closed cell MCC and transitioning to open cells or disorganized but cellular MCC are explored on timescales from 12 to 72 hr. Potential drivers of MCC transitions are shown to act on multiple timescales. Closed‐to‐open MCC cloud transitions are preceded by strong surface winds and large moisture fluxes at lead times of up to 72 hr; and by high cloud water content, reduced cloud drop concentrations, and intense rain rates at lead times of 12–36 hr. The relationship between intense rain and the formation of open cells is consistent with a cold pool convergence mechanism. A Lagrangian analysis shows that anomalously strong surface winds are associated with higher rain rates as well as subsequent increases in rain rates through modifications to moisture flux and content in the boundary layer. The closed‐open MCC transition contrasts with the closed‐to‐disorganized transition which at long lead times is associated with warm sea surface temperature and at diurnal‐scale lead times is associated with variables related to cloud top entrainment drying such as a deepening boundary layer, weakening subsidence and inversion strength, and a drier free troposphere. A conceptual model is proposed where excess boundary layer moisture associated with wind breaks up stratocumulus through the closed‐to‐open transition, while excess dry‐air entrainment at cloud top breaks up stratocumulus through the closed‐to‐disorganized transition.
Large Eddy Simulation for Investigating Coupled Forest Canopy and Turbulence Influences on Atmospheric Chemistry
Authors: Clifton Olivia E. , Patton Edward G. , Wang Siyuan , Barth Mary , Orlando John , Schwantes Rebecca H. 
Published: September 2022

AbstractExchanges of reactive gases between forests and the atmosphere influence tropospheric chemistry, climate, and ecosystems. Chemistry inside canopies can alter these exchanges yet understanding of the chemistry and processes influencing the chemistry is incomplete. Previous work prioritizes complex chemical mechanisms over micrometeorology in the multilayer models of forests used to understand in‐canopy chemistry and its impacts. Instead, here we use a new simplified chemical mechanism and resolve turbulence in a multilayer canopy model. Specifically, we describe a new version of the National Center for Atmospheric Research large eddy simulation (LES) coupled to both a multilayer canopy model and a chemical mechanism. The mechanism has 41 reactions and 19 gases for ozone, NOx (=NO + NO2), HOx (=OH + HO2), and isoprene chemistry. We evaluate the mechanism against two more complex mechanisms using box modeling. We configure the LES for a temperate deciduous forest and summer midday weak‐wind buoyancy‐forced conditions. The multilayer canopy model necessitates estimates of reactant sources and sinks at each canopy level, and thus we describe multilayer parameterizations for dry deposition and biogenic emissions. For the first time with an LES coupled to both a multilayer canopy and chemistry, we demonstrate variability in chemical reactions due to turbulence‐induced segregation of reactants inside and just above the canopy. For the cases examined here, in‐canopy segregation alters reaction rates that only consider well‐mixed conditions by up to −48% to +23%. For many reactions, segregation is stronger when soil NO emissions reflect the upper bound of observed values for temperate forests.
Prolonged Slip on the South Tibetan Detachment Constrains Tectonic Models for Synorogenic Extension in the Central Himalaya
Authors: Pye Alexandra E. , Hodges Kip V. , Keller C. Brenhin , Law Richard D. , van Soest Matthijs C. , Bhandari Basant , McDonald Christopher S. 
Published: September 2022

AbstractThe South Tibetan detachment system (STDS) is one of the most important deformational features in the Himalayan orogen; yet its evolution in space and time remain incompletely understood. Here, we present the results of a new study of the primary, basal strand of the STDS in the Annapurna Himalaya of central Nepal: the Annapurna detachment. The original discovery outcrop of this structure in the Kali Gandaki valley reveals that multiple leucogranite bodies are variably deformed by ductile slip on the detachment. New laser‐ablation (U‐Th)/Pb dating of complex monazite suites from these bodies indicates that leucogranites in this outcrop intruded over a period extending from at least 22.76 ± 0.30–14.95 ± 0.78 Ma. Field relationships and microstructures within studied samples show that ductile slip on the Annapurna detachment was active—at least episodically—throughout this period and also continued into the more recent past. Based on cooling history models for the outcrop constrained by 40Ar/39Ar and (U‐Th)/He data, ductile slip likely continued until at least 12 Ma. These results are at odds with previous inferences that slip on the STDS in central Nepal had ceased by ca. 22 Ma and call into question the popular idea that there was an abrupt geodynamic transition from predominantly N‐S‐directed extension to predominantly E‐W‐directed extension in the central Himalaya in the early Miocene.
Pharmacogenetic profiling via genome sequencing in children with medical complexity
Authors: Pan Amy , Scodellaro Sierra , Khan Tayyaba , Ushcatz Inna , Wu Wendy , Curtis Meredith , Cohen Eyal , Cohn Ronald D. , Hayeems Robin Z. , Meyn M. Stephen , Orkin Julia , Otal Jaskiran , Reuter Miriam S. , Walker Susan , Scherer Stephen W. , Marshall Christian R. , Cohn Iris , Costain Gregory 
Published: September 2022

AbstractBackgroundChildren with medical complexity (CMC) are a priority pediatric population, with high resource use and associated costs. Genome-wide sequencing is increasingly organized for CMC early in life as a diagnostic test. Polypharmacy becomes common as CMC age. Clinically relevant pharmacogenetic (PGx) information can be extracted from existing genome sequencing (GS) data via GS-PGx profiling. The role of GS-PGx profiling in the CMC population is unclear.MethodsPrescribed medications were extracted from care plans of 802 eligible CMC enrolled in a structured Complex Care Program over a 10-year period. Drug-gene associations were annotated using curated Clinical Pharmacogenetics Implementation Consortium data. GS-PGx profiling was then performed for a subset of 50 CMC.ResultsOverall, 546 CMC (68%) were prescribed at least one medication with an established PGx association. In the GS-PGx subgroup, 24 (48%) carried variants in pharmacogenes with drug-gene guidelines for one or more of their current medications. All had findings of potential relevance to some medications, including 32 (64%) with variants inCYP2C19that could affect their metabolism of proton-pump inhibitors.ConclusionGS-PGx profiling at the time of diagnostics-focused genetic testing could be an efficient way to incorporate precision prescribing practices into the lifelong care of CMC.ImpactPolypharmacy and genetic test utilization are both common in children with medical complexity.The role of repurposing genome sequencing data for pharmacogenetic profiling in children with medical complexity was previously unclear.We identified a high rate of medication use with clinically relevant drug-gene associations in this priority pediatric population and demonstrated that relevant pharmacogenetic information can be extracted from their existing genome sequencing data.Pharmacogenetic profiling at the time of diagnostics-focused genetic testing could be an efficient way to incorporate precision prescribing practices into the lifelong care of children with medical complexity.
Cryo-EM structures of human m6A writer complexes
Authors: Su Shichen , Li Shanshan , Deng Ting , Gao Minsong , Yin Yue , Wu Baixing , Peng Chao , Liu Jianzhao , Ma Jinbiao , Zhang Kaiming 
Published: September 2022

AbstractN6-methyladenosine (m6A) is the most abundant ribonucleotide modification among eukaryotic messenger RNAs. The m6A “writer” consists of the catalytic subunit m6A-METTL complex (MAC) and the regulatory subunit m6A-METTL-associated complex (MACOM), the latter being essential for enzymatic activity. Here, we report the cryo-electron microscopy (cryo-EM) structures of MACOM at a 3.0-Å resolution, uncovering that WTAP and VIRMA form the core structure of MACOM and that ZC3H13 stretches the conformation by binding VIRMA. Furthermore, the 4.4-Å resolution cryo-EM map of the MACOM–MAC complex, combined with crosslinking mass spectrometry and GST pull-down analysis, elucidates a plausible model of the m6A writer complex, in which MACOM binds to MAC mainly through WTAP and METTL3 interactions. In combination with in vitro RNA substrate binding and m6A methyltransferase activity assays, our results illustrate the molecular basis of how MACOM assembles and interacts with MAC to form an active m6A writer complex.
In situ small-angle X-ray scattering reveals strong condensation of DNA origami during silicification
Authors: Ober Martina F. , Baptist Anna , Wassermann Lea , Heuer-Jungemann Amelie , Nickel Bert 
Published: September 2022

AbstractSilicification of DNA origami structures increases their stability and provides chemical protection. Yet, it is unclear whether the whole DNA framework is embedded or if silica just forms an outer shell and how silicification affects the origami’s internal structure. Employing in situ small-angle X-ray scattering (SAXS), we show that addition of silica precursors induces substantial condensation of the DNA origami at early reaction times by almost 10 %. Subsequently, the overall size of the silicified DNA origami increases again due to increasing silica deposition. We further identify the SAXS Porod invariant as a reliable, model-free parameter for the evaluation of the amount of silica formation at a given time. Contrast matching of the DNA double helix Lorentzian peak reveals silica growth also inside the origami. The less polar silica forming within the origami structure, replacing more than 40 % of the internal hydration water, causes a hydrophobic effect: condensation. DNA origami objects with flat surfaces show a strong tendency towards aggregation during silicification, presumably driven by the same entropic forces causing condensation. Maximally condensed origami displayed thermal stability up to 60 °C. Our studies provide insights into the silicification reaction allowing for the formulation of optimized reaction protocols.
Combined IgE neutralization and Bifidobacterium longum supplementation reduces the allergic response in models of food allergy
Authors: An Seong Beom , Yang Bo-Gie , Jang Gyeonghui , Kim Do-Yeon , Kim Jiyoung , Oh Sung-Man , Oh Nahyun , Lee Sanghee , Moon Ji-Yeong , Kim Jeong-Ah , Kim Ji-Hyun , Song Yoo-Jeong , Hyun Hye-Won , Kim Jisoo , Lee Kyungwha , Lee Dajeong , Kwak Min-Jung , Kim Byung Kwon , Park Young-Kyu , Hong Chun-Pyo , Kim Jung Hwan , Lim Hye Seong , Ryu Min Sook , Jin Hyun-Tak , Lee Seung-Woo , Chang Yoon-Seok , Park Hae-Sim , Sung Young Chul , Jang Myoung Ho 
Published: September 2022

AbstractIgE is central to the development of allergic diseases, and its neutralization alleviates allergic symptoms. However, most of these antibodies are based on IgG1, which is associated with an increased risk of fragment crystallizable-mediated side effects. Moreover, omalizumab, an anti-IgE antibody approved for therapeutic use, has limited benefits for patients with high IgE levels. Here, we assess a fusion protein with extracellular domain of high affinity IgE receptor, FcεRIα, linked to a IgD/IgG4 hybrid Fc domain we term IgETRAP, to reduce the risk of IgG1 Fc-mediated side effects. IgETRAP shows enhanced IgE binding affinity compared to omalizumab. We also see an enhanced therapeutic effect of IgETRAP in food allergy models when combined with Bifidobacterium longum, which results in mast cell number and free IgE levels. The combination of IgETRAP and B. longum may therefore represent a potent treatment for allergic patients with high IgE levels.
Highly reinforced and degradable lignocellulose biocomposites by polymerization of new polyester oligomers
Authors: Oliaei Erfan , Olsén Peter , Lindström Tom , Berglund Lars A. 
Published: September 2022

AbstractUnbleached wood fibers and nanofibers are environmentally friendly bio-based candidates for material production, in particular, as reinforcements in polymer matrix biocomposites due to their low density and potential as carbon sink during the materials production phase. However, producing high reinforcement content biocomposites with degradable or chemically recyclable matrices is troublesome. Here, we address this issue with a new concept for facile and scalable in-situ polymerization of polyester matrices based on functionally balanced oligomers in pre-formed lignocellulosic networks. The idea enabled us to create high reinforcement biocomposites with well-dispersed mechanically undamaged fibers or nanocellulose. These degradable biocomposites have much higher mechanical properties than analogs in the literature. Reinforcement geometry (fibers at 30 µm or fibrils at 10–1000 nm diameter) influenced the polymerization and degradation of the polyester matrix. Overall, this work opens up new pathways toward environmentally benign materials in the context of a circular bioeconomy.
Gene expression based inference of cancer drug sensitivity
Authors: Chawla Smriti , Rockstroh Anja , Lehman Melanie , Ratther Ellca , Jain Atishay , Anand Anuneet , Gupta Apoorva , Bhattacharya Namrata , Poonia Sarita , Rai Priyadarshini , Das Nirjhar , Majumdar Angshul , Jayadeva  , Ahuja Gaurav , Hollier Brett G. , Nelson Colleen C. , Sengupta Debarka 
Published: September 2022

AbstractInter and intra-tumoral heterogeneity are major stumbling blocks in the treatment of cancer and are responsible for imparting differential drug responses in cancer patients. Recently, the availability of high-throughput screening datasets has paved the way for machine learning based personalized therapy recommendations using the molecular profiles of cancer specimens. In this study, we introduce Precily, a predictive modeling approach to infer treatment response in cancers using gene expression data. In this context, we demonstrate the benefits of considering pathway activity estimates in tandem with drug descriptors as features. We apply Precily on single-cell and bulk RNA sequencing data associated with hundreds of cancer cell lines. We then assess the predictability of treatment outcomes using our in-house prostate cancer cell line and xenografts datasets exposed to differential treatment conditions. Further, we demonstrate the applicability of our approach on patient drug response data from The Cancer Genome Atlas and an independent clinical study describing the treatment journey of three melanoma patients. Our findings highlight the importance of chemo-transcriptomics approaches in cancer treatment selection.
Structural basis for the activity regulation of a potassium channel AKT1 from Arabidopsis
Authors: Lu Yaming , Yu Miao , Jia Yutian , Yang Fan , Zhang Yanming , Xu Xia , Li Xiaomin , Yang Fan , Lei Jianlin , Wang Yi , Yang Guanghui 
Published: September 2022

AbstractThe voltage-gated potassium channel AKT1 is responsible for primary K+ uptake in Arabidopsis roots. AKT1 is functionally activated through phosphorylation and negatively regulated by a potassium channel α-subunit AtKC1. However, the molecular basis for the modulation mechanism remains unclear. Here we report the structures of AKT1, phosphorylated-AKT1, a constitutively-active variant, and AKT1-AtKC1 complex. AKT1 is assembled in 2-fold symmetry at the cytoplasmic domain. Such organization appears to sterically hinder the reorientation of C-linkers during ion permeation. Phosphorylated-AKT1 adopts an alternate 4-fold symmetric conformation at cytoplasmic domain, which indicates conformational changes associated with symmetry switch during channel activation. To corroborate this finding, we perform structure-guided mutagenesis to disrupt the dimeric interface and identify a constitutively-active variant Asp379Ala mediates K+ permeation independently of phosphorylation. This variant predominantly adopts a 4-fold symmetric conformation. Furthermore, the AKT1-AtKC1 complex assembles in 2-fold symmetry. Together, our work reveals structural insight into the regulatory mechanism for AKT1.
The transcription factor Zfh1 acts as a wing-morph switch in planthoppers
Authors: Zhang Jin-Li , Chen Sun-Jie , Liu Xin-Yang , Moczek Armin P. , Xu Hai-Jun 
Published: September 2022

AbstractInsect wing polyphenism is characterized by its ability to produce two or more distinct wing morphs from a single genotype in response to changing environments. However, the molecular basis of this phenomenon remains poorly understood. Here, we identified a zinc finger homeodomain transcription factor Zfh1 that acts as an upstream regulator for the development of long-winged (LW) or shorted-winged (SW) morphs in planthoppers. Knockdown of Zfh1 directs SW-destined nymphs to develop into LW morphs by down-regulating the transcriptional level of FoxO, a prominent downstream effector of the insulin/IGF signaling (IIS) pathway. The balance between transcriptional regulation via the Zfh1-FoxO cascade and post-translational regulation via the IIS-FoxO cascade provides a flexible regulatory mechanism for the development of alternative wing morphs. These findings help us understand how phenotypic diversity is generated by altering the activity of conserved proteins, and provide an extended framework for the evolution of wing morphological diversity in insects.
Accelerated sulfate reducing bacteria corrosion of X80 pipeline steel welded joints under organic carbon source starvation
Authors: Wang Qin , Zhou Xiaobao , Su Hui , Zhang Minghua , Li Zhi , Wu Tangqing 
Published: September 2022

AbstractSulfate-reducing bacteria (SRB) corrosion of X80 steel welded joint under organic carbon source starvation was investigated in the paper. The results showed that the number of planktonic cells is much less than that of sessile cells after 720 h immersion. The number of sessile cells in the base metal (BM) in the medium with 1% carbon source is the largest. Starving SRB cells accelerated simultaneously the uniform corrosion and localized corrosion of the welded joints, and the acceleration effect on the latter was much higher than that of the former. In all mediums, the density and average depth of pits in the BM and weld zone (WZ) were much larger than those in the heat affected zone (HAZ). SRB corrosion of the welded joint was strongly selective, and organic carbon source starvation further enhanced the selectivity.
Integrin-specific hydrogels for growth factor-free vasculogenesis
Authors: Moreira Helena R. , Rodrigues Daniel B. , Freitas-Ribeiro Sara , da Silva Lucília P. , da S. Morais Alain , Jarnalo Mariana , Horta Ricardo , Reis Rui L. , Pirraco Rogério P. , Marques Alexandra P. 
Published: September 2022

AbstractIntegrin-binding biomaterials have been extensively evaluated for their capacity to enable de novo formation of capillary-like structures/vessels, ultimately supporting neovascularization in vivo. Yet, the role of integrins as vascular initiators in engineered materials is still not well understood. Here, we show that αvβ3 integrin-specific 3D matrices were able to retain PECAM1+ cells from the stromal vascular fraction (SVF) of adipose tissue, triggering vasculogenesis in vitro in the absence of extrinsic growth factors. Our results suggest that αvβ3-RGD-driven signaling in the formation of capillary-like structures prevents the activation of the caspase 8 pathway and activates the FAK/paxillin pathway, both responsible for endothelial cells (ECs) survival and migration. We also show that prevascularized αvβ3 integrin-specific constructs inosculate with the host vascular system fostering in vivo neovascularization. Overall, this work demonstrates the ability of the biomaterial to trigger vasculogenesis in an integrin-specific manner, by activating essential pathways for EC survival and migration within a self-regulatory growth factor microenvironment. This strategy represents an improvement to current vascularization routes for Tissue Engineering constructs, potentially enhancing their clinical applicability.
Targeting and ultrabroad insight into molecular basis of Resistance-nodulation-cell division efflux pumps
Authors: Seyedhosseini Ghaheh Hooria , Damavandi Mohammad Sadegh , Sadeghi Parisa , Massah Ahmad Reza , Asl Taravat Hamidi , Salari-Jazi Azhar , Hejazi Seyed Hossein 
Published: September 2022

AbstractResistance-nodulation-cell devision (RND) efflux pump variants have attracted a great deal of attention for efflux of many antibiotic classes, which leads to multidrug-resistant bacteria. The present study aimed to discover the interaction between the RND efflux pumps and antibiotics, find the conserved and hot spot residues, and use this information to target the most frequent RND efflux pumps. Protein sequence and 3D conformational alignments, pharmacophore modeling, molecular docking, and molecular dynamics simulation were used in the first level for discovering the function of the residues in interaction with antibiotics. In the second level, pharmacophore-based screening, structural-based screening, multistep docking, GRID MIF, pharmacokinetic modeling, fragment molecular orbital, and MD simulation were utilized alongside the former level information to find the most proper inhibitors. Five conserved residues, containing Ala209, Tyr404, Leu415, Asp416, and Ala417, as well as their counterparts in other OMPs were evaluated as the crucial conserved residues. MD simulation confirmed that a number of these residues had a key role in the performance of the efflux antibiotics; therefore, some of them were hot spot residues. Fourteen ligands were selected, four of which interacted with all the crucial conserved residues. NPC100251 was the fittest OMP inhibitor after pharmacokinetic computations. The second-level MD simulation and FMO supported the efficacy of the NPC100251. It was exhibited that perhaps OMPs worked as the intelligent and programable protein. NPC100251 was the strongest OMPs inhibitor, and may be a potential therapeutic candidate for MDR infections.
The reliability, validity and usefulness of the 30–15 intermittent fitness test for cardiorespiratory fitness assessment in military personnel
Authors: Paravlic Armin H. , Simunic Bostjan , Pisot Rado , Rauter Samo , Stuhec Stanko , Vodicar Janez 
Published: September 2022

AbstractThe objectives of this study were to investigate the reliability, validity, and usefulness of the 30–15 intermittent fitness test (30–15IFT) in soldiers. The 34 infantry members of the Slovenian armed forces were recruited as participants. Participants performed the continuous incremental treadmill test (TR), a 2-mile run (2MR) test, and two 30–15IFT tests. Additionally, participants were divided into a highest-scoring group (HSG) and a lowest-scoring group (LSG) based on their scores on the Army Physical Fitness Test. A very high reliability ratings were observed for 30–15IFT measures, as follows: end-running speed (ERS) ERSIFT (ICC = 0.971), maximal heart rate (HRmax) HRmaxIFT (IC = 0.960), and maximal relative oxygen consumption (VO2max) VO2max-IFT (ICC = 0.975). Although 30–15IFT measures demonstrated high correlations (r = 0.695–0.930) to the same measures of TR test, ERS, HRmax and VO2max were higher in the 30–15IFT (p > 0.05). Furthermore, ERSIFT and predicted VO2maxIFT were higher in HSG compared to LSG, whereas HRmax did not differ. The results of this study show that the 30–15IFT test is a reliable, valid and useful tool for assessing cardiorespiratory fitness in the armed forces. Moreover, the ERS and predicted VO2max values derived from the 30–15IFT could be considered more sensitive markers of combat readiness than the parameters derived from the TR and 2MR tests.Trial registration number: NCT05218798.