bluuebunny/crossref_metadata_2025_split huggingface dataset:
Near‐Bed Structure of Sediment Gravity Flows Measured by Motion‐Sensing “Boulder‐Like” Benthic Event Detectors (BEDs) in Monterey Canyon
Authors: Gwiazda R. , Paull C. K. , Kieft B. , Klimov D. , Herlien R. , Lundsten E. , McCann M. , Cartigny Matthieu J. , Hamilton A. , Xu J. , Maier Katherine L. , Parsons D. R. , Talling Peter J. 
Published: January 2022

AbstractThe near‐bed section of submarine gravity flows travels at the highest and most destructive speeds making direct measurements of this region of the flow difficult. Here results are presented from “boulder‐like” Benthic Event Detectors (BEDs) that measured their own rotation, depth and temperature while carried within the near‐bed region of gravity flows. BEDs were deployed in Monterey Canyon from 200 to 500 m water depth for 18 months (2016–2017) during the Coordinated Canyon Experiment. BEDs moved in 10 out of 14 gravity flows that transited the upper canyon. BEDs moved within the body of the flow because the initial velocities of the BEDs were 66 ± 16% (1 SD) of the flow transit velocities. BEDs rotated freely during most of their first moves and gained depth faster than in later moves, when their motion was more random and wobblier. The differences in BED motions between first and later moves suggest BEDs moved at different depths within the flow. The inferred near‐bed flow structure is strongly stratified with a fast, less‐dense layer moving above a slower and denser layer. Coherent changes between pressure and acceleration indicate that BEDs rode a crescent shaped bedform (CSB) morphology that persisted throughout flow events. The variability in BED speeds while riding the CSB morphology indicates a fluid‐like nature of the near‐bed layer. BED motions ended after being caught in the trough of a CSB. Based on recorded temperature decay rates after flow events, the thickness of redeposited sediment is 2–3 m.
Antecedent Conditions Control Thresholds of Tile‐Runoff Generation and Nitrogen Export in Intensively Managed Landscapes
Authors: Cain Molly R. , Woo Dong Kook , Kumar Praveen , Keefer Laura , Ward Adam S. 
Published: January 2022

AbstractThreshold changes in rainfall‐runoff generation commonly represent shifts in runoff mechanisms and hydrologic connectivity controlling water and solute transport and transformation. In watersheds with limited human influence, threshold runoff responses reflect interaction between precipitation event and antecedent soil moisture. Similar analyses are lacking in intensively managed landscapes where installation of subsurface drainage tiles has altered connectivity between the land surface, groundwater, and streams, and where application of fertilizer has created significant stores of subsurface nitrogen. In this study, we identify threshold patterns of tile‐runoff generation for a drained agricultural field in Illinois and evaluate how antecedent conditions—including shallow soil moisture, groundwater table depth, and the presence or absence of crops—control tile response. We relate tile‐runoff thresholds to patterns of event nitrate load observed across multiple storm events and evaluate how antecedent conditions control within‐event nitrate concentration‐discharge relationships. Our results demonstrate that an event tile‐runoff threshold emerges relative to the sum of gross precipitation and indices of antecedent shallow soil moisture and antecedent below‐tile groundwater moisture deficit, indicating that both shallow soil and below‐tile storages must be filled to generate significant runoff. In turn, event nitrate load shows a linear dependence on runoff for most time periods, suggesting that subsurface nitrate export and storage can be estimated using runoff threshold relationships and long‐term average nitrate concentrations. Finally, within‐event nitrate concentration‐discharge relationships are controlled by event size and the antecedent tile flow state because these factors dictate the sequence of flow path activation and tile connectivity over a storm event.
Human microRNA (miR-20b-5p) modulates Alzheimer’s disease pathways and neuronal function, and a specific polymorphism close to the MIR20B gene influences Alzheimer’s biomarkers
Authors: Wang Ruizhi , Chopra Nipun , Nho Kwangsik , Maloney Bryan , Obukhov Alexander G. , Nelson Peter T. , Counts Scott E. , Lahiri Debomoy K. 
Published: January 2022

AbstractAlzheimer’s disease (AD) is a progressive neurodegenerative disorder with loss of cognitive, executive, and other mental functions, and is the most common form of age-related dementia. Amyloid-β peptide (Aβ) contributes to the etiology and progression of the disease. Aβ is derived from the amyloid-β precursor protein (APP). Multiple microRNA (miRNA) species are also implicated in AD. We report that human hsa-miR20b-5p (miR-20b), produced from the MIR20B gene on Chromosome X, may play complex roles in AD pathogenesis, including Aβ regulation. Specifically, miR-20b-5p miRNA levels were altered in association with disease progression in three regions of the human brain: temporal neocortex, cerebellum, and posterior cingulate cortex. In cultured human neuronal cells, miR-20b-5p treatment interfered with calcium homeostasis, neurite outgrowth, and branchpoints. A single-nucleotide polymorphism (SNP) upstream of the MIR20B gene (rs13897515) associated with differences in levels of cerebrospinal fluid (CSF) Aβ1-42 and thickness of the entorhinal cortex. We located a miR-20b-5p binding site in the APP mRNA 3′-untranslated region (UTR), and treatment with miR-20b-5p reduced APP mRNA and protein levels. Network analysis of protein-protein interactions and gene coexpression revealed other important potential miR-20b-5p targets among AD-related proteins/genes. MiR-20b-5p, a miRNA that downregulated APP, was paradoxically associated with an increased risk for AD. However, miR-20b-5p also reduced, and the blockade of APP by siRNA likewise reduced calcium influx. As APP plays vital roles in neuronal health and does not exist solely to be the source of “pathogenic” Aβ, the molecular etiology of AD is likely to not just be a disease of “excess” but a disruption of delicate homeostasis.
Long-term oral administration of an HNF4α agonist prevents weight gain and hepatic steatosis by promoting increased mitochondrial mass and function
Authors: Veeriah Vimal , Lee Seung-Hee , Levine Fred 
Published: January 2022

AbstractWe report here that the potent HNF4α agonist N-trans-caffeoyltyramine (NCT) promotes weight loss by inducing an increase in mitochondrial mass and function, including fatty acid oxidation. Previously, we found in a short term trial in obese mice that NCT promoted reversal of hepatic steatosis through a mechanism involving the stimulation of lipophagy by dihydroceramides. NCT led to increased dihydroceramide levels by inhibiting dihydroceramide conversion to ceramides. Here, we were able to administer NCT orally, permitting longer term administration. Mice fed NCT mixed with high fat diet exhibited decreased weight. Examination of RNA-seq data revealed an increase in PPARGC1A, a central regulator of mitochondrial biogenesis. In addition to the decreased hepatic steatosis that we found previously, mice fed a high fat diet containing NCT mice weighed substantially less than control mice fed high fat diet alone. They had increased mitochondrial mass, exhibited increased fatty acid oxidation, and had an increased level of NAD. Markers of liver inflammation such as interleukin-6 (IL-6) and tumor necrosis factor alpha (TNFα), which are important in the progression of non-alcoholic fatty liver disease to non-alcoholic steatohepatitis were decreased by NCT. There was no evidence of any toxicity from NCT consumption. These results indicate that HNF4α is an important regulator of mitochondrial mass and function and support that use of HNF4α to treat disorders of fatty acid excess, potentially including obesity, NAFLD, and NASH.
Enhanced glycolysis in granulosa cells promotes the activation of primordial follicles through mTOR signaling
Authors: Zhang Xiaodan , Zhang Wenbo , Wang Zhijuan , Zheng Nana , Yuan Feifei , Li Biao , Li Xuelan , Deng Ling , Lin Min , Chen Xin , Zhang Meijia 
Published: January 2022

AbstractIn mammals, nonrenewable primordial follicles are activated in an orderly manner to maintain the longevity of reproductive life. Mammalian target of rapamycin (mTOR)-KIT ligand (KITL) signaling in pre-granulosa cells and phosphatidylinositol 3-kinase (PI3K)-protein kinase B (Akt)-forkhead Box O3a (FOXO3a) signaling in oocytes are important for primordial follicle activation. The activation process is accompanied by the enhancement of energy metabolism, but the causal relationship is unclear. In the present study, the levels of glycolysis-related proteins GLUT4, HK1, PFKL, and PKM2 were significantly increased in granulosa cells but were decreased in oocytes during the mouse primordial-to-primary follicle transition. Both short-term pyruvate deprivation in vitro and acute fasting in vivo increased the glycolysis-related gene and protein levels, decreased AMPK activity, and increased mTOR activity in mouse ovaries. The downstream pathways Akt and FOXO3a were phosphorylated, resulting in mouse primordial follicle activation. The blockade of glycolysis by 2-deoxyglucose (2-DG), but not the blockade of the communication network between pre-granulosa cells and oocyte by KIT inhibitor ISCK03, decreased short-term pyruvate deprivation-promoted mTOR activity. Glycolysis was also increased in human granulosa cells during the primordial-to-primary follicle transition, and short-term pyruvate deprivation promoted the activation of human primordial follicles by increasing the glycolysis-related protein levels and mTOR activity in ovarian tissues. Taken together, the enhanced glycolysis in granulosa cells promotes the activation of primordial follicles through mTOR signaling. These findings provide new insight into the relationship between glycolytic disorders and POI/PCOS.
Multiple conformations of trimeric spikes visualized on a non-enveloped virus
Authors: Zhang Yinong , Cui Yanxiang , Sun Jingchen , Zhou Z. Hong 
Published: January 2022

AbstractMany viruses utilize trimeric spikes to gain entry into host cells. However, without in situ structures of these trimeric spikes, a full understanding of this dynamic and essential process of viral infections is not possible. Here we present four in situ and one isolated cryoEM structures of the trimeric spike of the cytoplasmic polyhedrosis virus, a member of the non-envelopedReoviridaefamily and a virus historically used as a model in the discoveries of RNA transcription and capping. These structures adopt two drastically different conformations, closed spike and opened spike, which respectively represent the penetration-inactive and penetration-active states. Each spike monomer has four domains: N-terminal, body, claw, and C-terminal. From closed to opened state, the RGD motif-containing C-terminal domain is freed to bind integrins, and the claw domain rotates to expose and project its membrane insertion loops into the cellular membrane. Comparison between turret vertices before and after detachment of the trimeric spike shows that thetrimericspike anchors its N-terminal domain in the iris of thepentamericRNA-capping turret. Sensing of cytosolic S-adenosylmethionine (SAM) and adenosine triphosphate (ATP) by the turret triggers a cascade of events: opening of the iris, detachment of the spike, and initiation of endogenous transcription.
Population structure analysis and laboratory monitoring of Shigella by core-genome multilocus sequence typing
Authors: Yassine Iman , Lefèvre Sophie , Hansen Elisabeth E. , Ruckly Corinne , Carle Isabelle , Lejay-Collin Monique , Fabre Laëtitia , Rafei Rayane , Clermont Dominique , de la Gandara Maria Pardos , Dabboussi Fouad , Thomson Nicholas R. , Weill François-Xavier 
Published: January 2022

AbstractThe laboratory surveillance of bacillary dysentery is based on a standardisedShigellatyping scheme that classifiesShigellastrains into four serogroups and more than 50 serotypes on the basis of biochemical tests and lipopolysaccharide O-antigen serotyping. Real-time genomic surveillance ofShigellainfections has been implemented in several countries, but without the use of a standardised typing scheme. Here, we study over 4000 reference strains and clinical isolates ofShigella, covering all serotypes, with both the current serotyping scheme and the standardised EnteroBase core-genome multilocus sequence typing scheme (cgMLST). TheShigellagenomes are grouped into eight phylogenetically distinct clusters, within theE. colispecies. The cgMLST hierarchical clustering (HC) analysis at different levels of resolution (HC2000 to HC400) recognises the natural population structure ofShigella. By contrast, the serotyping scheme is affected by horizontal gene transfer, leading to a conflation of genetically unrelatedShigellastrains and a separation of genetically related strains. The use of this cgMLST scheme will facilitate the transition from traditional phenotypic typing to routine whole-genome sequencing for the laboratory surveillance ofShigellainfections.
Assessing the impact of SARS-CoV-2 prevention measures in Austrian schools using agent-based simulations and cluster tracing data
Authors: Lasser Jana , Sorger Johannes , Richter Lukas , Thurner Stefan , Schmid Daniela , Klimek Peter 
Published: January 2022

AbstractWe aim to identify those measures that effectively control the spread of SARS-CoV-2 in Austrian schools. Using cluster tracing data we calibrate an agent-based epidemiological model and consider situations where the B1.617.2 (delta) virus strain is dominant and parts of the population are vaccinated to quantify the impact of non-pharmaceutical interventions (NPIs) such as room ventilation, reduction of class size, wearing of masks during lessons, vaccinations, and school entry testing by SARS-CoV2-antigen tests. In the data we find that 40% of all clusters involved no more than two cases, and 3% of the clusters only had more than 20 cases. The model shows that combinations of NPIs together with vaccinations are necessary to allow for a controlled opening of schools under sustained community transmission of the SARS-CoV-2 delta variant. For plausible vaccination rates, primary (secondary) schools require a combination of at least two (three) of the above NPIs.
Non-telecentric two-photon microscopy for 3D random access mesoscale imaging
Authors: Janiak F. K. , Bartel P. , Bale M. R. , Yoshimatsu T. , Komulainen E. , Zhou M. , Staras K. , Prieto-Godino L. L. , Euler T. , Maravall M. , Baden T. 
Published: January 2022

AbstractDiffraction-limited two-photon microscopy permits minimally invasive optical monitoring of neuronal activity. However, most conventional two-photon microscopes impose significant constraints on the size of the imaging field-of-view and the specific shape of the effective excitation volume, thus limiting the scope of biological questions that can be addressed and the information obtainable. Here, employing a non-telecentric optical design, we present a low-cost, easily implemented and flexible solution to address these limitations, offering a several-fold expanded three-dimensional field of view. Moreover, rapid laser-focus control via an electrically tunable lens allows near-simultaneous imaging of remote regions separated in three dimensions and permits the bending of imaging planes to follow natural curvatures in biological structures. Crucially, our core design is readily implemented (and reversed) within a matter of hours, making it highly suitable as a base platform for further development. We demonstrate the application of our system for imaging neuronal activity in a variety of examples in zebrafish, mice and fruit flies.
Efficient, biosafe and tissue adhesive hemostatic cotton gauze with controlled balance of hydrophilicity and hydrophobicity
Authors: He Huaying , Zhou Weikang , Gao Jing , Wang Fan , Wang Shaobing , Fang Yan , Gao Yang , Chen Wei , Zhang Wen , Weng Yunxiang , Wang Zhengchao , Liu Haiqing 
Published: January 2022

AbstractCotton gauze is a widely used topical hemostatic material for bleeding control, but its high blood absorption capacity tends to cause extra blood loss. Therefore, development of rapid hemostatic cotton gauze with less blood loss is of great significance. Here, we develop an efficient hemostatic cotton gauze whose surface is slightly modified with a catechol compound which features a flexible long hydrophobic alkyl chain terminated with a catechol group. Its hemostatic performance in animal injuries is superior to standard cotton gauze and Combat GauzeTM. Its biosafety is similar to cotton gauze and rebleeding hardly occurs when the gauze is removed. Here, we show its hemostatic capability is attributable to the rapid formation of big and thick primary erythrocyte clots, due to its effective controlling of blood movement through blocking effect from tissue adhesion by catechol, blood wicking in cotton, and the hydrophobic effect from long alkyl chains.
Predicting elastic properties of hard-coating alloys using ab-initio and machine learning methods
Authors: Levämäki H. , Tasnádi F. , Sangiovanni D. G. , Johnson L. J. S. , Armiento R. , Abrikosov I. A. 
Published: January 2022

AbstractAccelerated design of hard-coating materials requires state-of-the-art computational tools, which include data-driven techniques, building databases, and training machine learning models. We develop a heavily automated high-throughput workflow to build a database of industrially relevant hard-coating materials, such as binary and ternary nitrides. We use the high-throughput toolkit to automate the density functional theory calculation workflow. We present results, including elastic constants that are a key parameter determining mechanical properties of hard-coatings, for X1−xYxN ternary nitrides, where X,Y ∈ {Al, Ti, Zr, Hf} and fraction $$x=0,\frac{1}{4},\frac{1}{2},\frac{3}{4},1$$

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. We also explore ways for machine learning to support and complement the designed databases. We find that the crystal graph convolutional neural network trained on ordered lattices has sufficient accuracy for the disordered nitrides, suggesting that existing databases provide important data for predicting mechanical properties of qualitatively different types of materials, in our case disordered hard-coating alloys.
An evaluation of pipelines for DNA variant detection can guide a reanalysis protocol to increase the diagnostic ratio of genetic diseases
Authors: Romero Raquel , de la Fuente Lorena , Del Pozo-Valero Marta , Riveiro-Álvarez Rosa , Trujillo-Tiebas María José , Martín-Mérida Inmaculada , Ávila-Fernández Almudena , Iancu Ionut-Florin , Perea-Romero Irene , Núñez-Moreno Gonzalo , Damián Alejandra , Rodilla Cristina , Almoguera Berta , Cortón Marta , Ayuso Carmen , Mínguez Pablo 
Published: January 2022

AbstractClinical exome (CE) sequencing has become a first-tier diagnostic test for hereditary diseases; however, its diagnostic rate is around 30–50%. In this study, we aimed to increase the diagnostic yield of CE using a custom reanalysis algorithm. Sequencing data were available for three cohorts using two commercial protocols applied as part of the diagnostic process. Using these cohorts, we compared the performance of general and clinically relevant variant calling and the efficacy of an in-house bioinformatic protocol (FJD-pipeline) in detecting causal variants as compared to commercial protocols. On the whole, the FJD-pipeline detected 99.74% of the causal variants identified by the commercial protocol in previously solved cases. In the unsolved cases, FJD-pipeline detects more INDELs and non-exonic variants, and is able to increase the diagnostic yield in 2.5% and 3.2% in the re-analysis of 78 cancer and 62 cardiovascular cases. These results were considered to design a reanalysis, filtering and prioritization algorithm that was tested by reassessing 68 inconclusive cases of monoallelic autosomal recessive retinal dystrophies increasing the diagnosis by 4.4%. In conclusion, a guided NGS reanalysis of unsolved cases increases the diagnostic yield in genetic disorders, making it a useful diagnostic tool in medical genetics.
3D printed leech-inspired origami dry electrodes for electrophysiology sensing robots
Authors: Kim Tae-Ho , Bao Chao , Chen Ziniu , Kim Woo Soo 
Published: January 2022

AbstractIn this study, based on inspiration drawn from origami and the suction mechanism of leeches, a dry electrode is developed for reliable blood pressure (BP) monitoring. The leech-inspired suction mechanism generated a local soft vacuum facilitating appropriate contact with the human skin. Subsequently, an electrocardiogram (ECG) sensor, termed a leech-inspired origami (LIO) sensor, was constructed using the developed dry electrode. The LIO with a sensing robot system ensures reliable ECG signals with a signal-to-noise ratio of 21.7 ± 0.56 dB. From the paired detection of ECG and photoplethysmography (PPG) through human–robot interaction, BP monitoring was demonstrated. The average difference of the systolic BP between that estimated by the sensing robot and that monitored by the sphygmomanometer was 0.03 mmHg, indicating the reliable BP monitoring ability of the sensing robot. The LIO sensing system inspired by origami and leech behaviors makes BP sensing tools feasible, which in turn would further the development of a remote healthcare monitoring robotic system.
Multi-objective optimization reveals time- and dose-dependent inflammatory cytokine-mediated regulation of human stem cell derived T-cell development
Authors: Edgar John M. , Michaels Yale S. , Zandstra Peter W. 
Published: January 2022

AbstractThe generation of T-cells from stem cells in vitro could provide an alternative source of cells for immunotherapies. T-cell development from hematopoietic stem and progenitor cells (HSPCs) is tightly regulated through Notch pathway activation by Delta-like (DL) ligands 1 and 4. Other molecules, such as stem cell factor (SCF) and interleukin (IL)-7, play a supportive role in regulating the survival, differentiation, and proliferation of developing T-cells. Numerous other signaling molecules influence T-lineage development in vivo, but little work has been done to understand and optimize their use for T-cell production. Using a defined engineered thymic niche system, we undertook a multi-stage statistical learning-based optimization campaign and identified IL-3 and tumor necrosis factor α (TNFα) as a stage- and dose-specific enhancers of cell proliferation and T-lineage differentiation. We used this information to construct an efficient three-stage process for generating conventional TCRαβ+CD8+T-cells expressing a diverse TCR repertoire from blood stem cells. Our work provides new insight into T-cell development and a robust system for generating T-cells to enable clinical therapies for treating cancer and immune disorders.