bluuebunny/crossref_metadata_2025_split huggingface dataset:
Uncertainty Analysis for Hydrological Models With Interdependent Parameters: An Improved Polynomial Chaos Expansion Approach
Authors: Ghaith Maysara , Li Zhong , Baetz Brian W. 
Published: July 2021

AbstractThe use of polynomial chaos expansion (PCE) has gained a lot of attention due to its ability to efficiently estimate the effects of parameter uncertainty on model outputs. The traditional PCE technique requires the studied parameters to be independent. In hydrological modeling, although model parameters are often assumed to be independent for simplicity of computation, such an assumption is not always valid. Neglecting parameter correlations could significantly affect the analysis of uncertainty, leading to distorted modeling results. In this study, an improved PCE approach is proposed to address this issue and support the uncertainty analysis for hydrological models with correlated parameters. The proposed approach is based on the integration of principle component analysis (PCA) and PCE, where PCA is used to transform correlated parameters into orthogonal independent components. To demonstrate the applicability of this approach, the Soil & Water Assessment Tool (SWAT) model is applied to the Guadalupe River Watershed in Texas, US, and the integrated PCA‐PCE framework is used to assess the propagation of uncertainty of SWAT's interdependent parameters. A traditional Monte‐Carlo (MC) simulation is also used to address the uncertainty in the developed SWAT model. The results show that PCA‐PCE could generate similar probabilistic flow results compared to MC while maintaining a very high computational efficiency. The coefficients of determination (R2) for the mean and variance are 0.998 and 0.973, respectively, and the computational requirement is reduced by 99% using the developed PCA‐PCE approach. It is shown that the PCA‐PCE approach is reliable and efficient in assessing uncertainties in hydrological models with interdependent parameters.
A Rusty Record of Weathering and Groundwater Movement in the Hyperarid Central Andes
Authors: Shaw J. M. , Evenstar L. , Cooper F. J. , Adams B. A. , Boyce A. J. , Hofmann F. , Farley K. A. 
Published: July 2021

AbstractThe Atacama Desert, on the western margin of the Central Andes, hosts some of the world's largest porphyry copper deposits (PCDs). Despite a hyperarid climate, many of these PCDs have undergone secondary “supergene” enrichment, whereby copper has been concentrated via groundwater‐driven leaching and reprecipitation, yielding supergene profiles containing valuable records of weathering and landscape evolution. We combine hematite (U‐Th‐Sm)/He geochronology and oxygen isotope analysis to compare the weathering histories of two Andean PCDs and test the relative importance of climate and tectonics in controlling both enrichment and water table movement. At Cerro Colorado, in the Precordillera, hematite precipitation records prolonged weathering from ∼31 to ∼2 Ma, tracking water table descent following aridity‐induced canyon incision from the late Miocene onward. By contrast, hematite at Spence, within the Central Depression, is mostly younger than ∼10.5 Ma, suggesting exhumation ended much later. A heavy oxygen isotopic signature for Spence hematite suggests that upwelling formation water has been an important source of groundwater, accounting for a high modern water table despite persistent hyperaridity, whereas isotopically light hematite at Cerro Colorado formed in the presence of meteoric water. Compared with published paleo‐environmental and sedimentological records, our data show that weathering can persist beneath appreciable post‐exhumation cover, under hyperarid conditions unconducive to enrichment. The susceptibility of each deposit to aridity‐induced water table descent, canyon incision and deep weathering has been controlled by recharge characteristics and morphotectonic setting. Erosional exhumation, rather than aridity‐induced water table decay, appears to be more important for the development of supergene enrichment.
Mixed‐Phase Clouds Over the Southern Ocean as Observed From Satellite and Surface Based Lidar and Radar
Authors: Mace Gerald G. , Protat Alain , Benson Sally 
Published: July 2021

AbstractThis study investigates the occurrence of mixed‐phase clouds (MPC, i.e., cloud layers containing both liquid and ice water at sub‐freezing temperatures) over the Southern Ocean (SO) using space‐ and surface‐based lidar and radar observations. The occurrence of supercooled clouds is dominated by geometrically thin (<1 km) layers that rarely contain ice. We diagnose layers that are geometrically thicker than 1 km to contain ice ~65% and ~4% of the time from below by surface remote sensors and from above by orbiting remote sensors, respectively. We examine the discrepancy in MPC occurrence statistics as diagnosed from below and above the cloud layer. From above, we find that MPC occurrence has a gradient associated with the Antarctic Polar Front near 55°S with a rare occurrence of satellite‐derived MPC south of that latitude. In contrast, surface sensors find ice in 33% of supercooled liquid water layers. We infer using observing system simulation experiments and data analysis that space‐based lidar cannot identify the occurrence of MPC except when secondary ice‐forming processes operate in convection that is, sufficiently strong to loft ice crystals to cloud tops. We conclude that the CALIPSO phase statistics of MPC have a severe low bias in MPC occurrence. Based on surface‐based statistics in the SO, we present a parameterization of the frequency of MPC as a function of cloud top temperature that differs substantially from that used in recent climate model simulations.
Deep Ocean Storage of Heat and CO2 in the Fram Strait, Arctic Ocean During the Last Glacial Period
Authors: Ezat Mohamed M. , Rasmussen Tine L. , Hain Mathis P. , Greaves Mervyn , Rae James W. B. , Zamelczyk Katarzyna , Marchitto Thomas M. , Szidat Sönke , Skinner Luke C. 
Published: July 2021

AbstractThe Fram Strait is the only deep gateway between the Arctic Ocean and the Nordic Seas and thus is a key area to study past changes in ocean circulation and the marine carbon cycle. Here, we study deep ocean temperature, δ18O, carbonate chemistry (i.e., carbonate ion concentration [CO32−]), and nutrient content in the Fram Strait during the late glacial (35,000–19,000 years BP) and the Holocene based on benthic foraminiferal geochemistry and carbon cycle modeling. Our results indicate a thickening of Atlantic water penetrating into the northern Nordic Seas, forming a subsurface Atlantic intermediate water layer reaching to at least ∼2,600 m water depth during most of the late glacial period. The recirculating Atlantic layer was characterized by relatively high [CO32−] and low δ13C during the late glacial, and provides evidence for a Nordic Seas source to the glacial North Atlantic intermediate water flowing at 2,000–3,000 m water depth, most likely via the Denmark Strait. In addition, we discuss evidence for enhanced terrestrial carbon input to the Nordic Seas at ∼23.5 ka. Comparing our δ13C and qualitative [CO32−] records with results of carbon cycle box modeling suggests that the total terrestrial CO2 release during this carbon input event was low, slow, or directly to the atmosphere.
A Multi‐Purpose Heliophysics L4 Mission
Authors: Posner A. , Arge C. N. , Staub J. , StCyr O. C. , Folta D. , Solanki S. K. , Strauss R. D. T. , Effenberger F. , Gandorfer A. , Heber B. , Henney C. J. , Hirzberger J. , Jones S. I. , Kühl P. , Malandraki O. , Sterken V. J. 
Published: July 2021

AbstractThe Earth‐Sun Lagrangian point 4 is a meta‐stable location at 1 AU from the Sun, 60° ahead of Earth's orbit. It has an uninterrupted view of the solar photosphere centered on W60, the Earth's nominal magnetic field connection to the Sun. Such a mission on its own would serve as a solar remote sensing observatory that would oversee the entire solar radiation hemisphere with significant relevance for protecting Moon and Mars explorers from radiation exposure. In combination with appropriately planned observatories at L1 and L5, the three spacecraft would provide 300° longitude coverage of photospheric magnetic field structure, and allow continuous viewing of both solar poles, with >3.6° elevation. Ideally, the L4 and L5 missions would orbit the Sun with a 7.2° inclination out of the heliographic equator, 14.5° out of the ecliptic plane. We discuss the impact of extending solar magnetic field observations in both longitude and latitude to improve global solar wind modeling and, with the development of local helioseismology, the potential for long‐term solar activity forecasting. Such a mission would provide a unique opportunity for interplanetary and interstellar dust science. It would significantly add to reliability of operational observations on fast coronal mass ejections directed at Earth and for human Mars explorers on their round‐trip journey. The L4 mission concept is technically feasible, and is scientifically compelling.
High-throughput sequencing identified circular RNA circUBE2K mediating RhoA associated bladder cancer phenotype via regulation of miR-516b-5p/ARHGAP5 axis
Authors: Yang Chen , Mou Zezhong , Wu Siqi , Ou Yuxi , Zhang Zheyu , Chen Xinan , Dai Xiyu , Xu Chenyang , Mao Shanhua , Jiang Haowen 
Published: July 2021

AbstractBladder cancer (BC) is known as a common and lethal urinary malignancy worldwide. Circular RNAs (circRNAs), an emerging non-coding RNA, participate in carcinogenesis process of several cancers including BC. In this study, high-throughput sequencing and RT-qPCR were applied to discover and validate abnormal high expression of circUBE2K in BC tissues. Fluorescence in situ hybridization (FISH) was used to detect hsa_circ_0009154 (circUBE2K) expression and subcellular localization in BC tissues. High circUBE2K predicted unfavorable prognoses in BCs, as well as correlated with clinical features. CCK8, transwell, EdU and wound healing assays demonstrated down-regulating circUBE2K decreased BC cell phenotype as proliferation, invasion, and migration, respectively. Further studies showed that circUBE2K promoted BC progression via sponging miR-516b-5p and enhancing ARHGAP5 expression through regulating RhoA activity. Dual-luciferase reporter, FISH and RNA pulldown assays were employed to verify the relationships among circUBE2K/miR-516b-5p/ARHGAP5/RhoA axis. Down-regulating miR-516b-5p or overexpressing ARHGAP5 restored RhoA activity mediated BC cell properties after silencing circUBE2K. Subcutaneous xenograft and metastasis model identified circUBE2K significantly increased BC cell metastasis and proliferation in-vivo. Taken together, we found that circUBE2K is a tumor-promoting circRNA in BC that functions as a ceRNA to regulate ARHGAP5 expression via sponging miR-516b-5p.
A novel LRP6 variant in a Japanese family with oligodontia
Authors: Goto Hiroki , Kimura Masashi , Machida Junichiro , Ota Akiko , Nakashima Mitsuko , Tsuchida Naomi , Adachi Junya , Aoki Yoshihiko , Tatematsu Tadashi , Takahashi Katsu , Sana Masatoshi , Nakayama Atsuo , Suzuki Shintaro , Nagao Toru , Matsumoto Naomichi , Tokita Yoshihito 
Published: July 2021

AbstractCongenital tooth agenesis is a common anomaly in human development. We performed exome sequence analysis of genomic DNA collected from Japanese patients with tooth agenesis and their relatives. We found a novel single-nucleotide insertion in the LRP6 gene, the product of which is involved in Wnt/β-catenin signaling as a coreceptor for Wnt ligands. The single-nucleotide insertion results in a premature stop codon in the extracellular region of the encoded protein.
Contextualizing genetic risk score for disease screening and rare variant discovery
Authors: Zhou Dan , Yu Dongmei , Scharf Jeremiah M. , Mathews Carol A. , McGrath Lauren , Cook Edwin , Lee S. Hong , Davis Lea K. , Gamazon Eric R. 
Published: July 2021

AbstractStudies of the genetic basis of complex traits have demonstrated a substantial role for common, small-effect variant polygenic burden (PB) as well as large-effect variants (LEV, primarily rare). We identify sufficient conditions in which GWAS-derived PB may be used for well-powered rare pathogenic variant discovery or as a sample prioritization tool for whole-genome or exome sequencing. Through extensive simulations of genetic architectures and generative models of disease liability with parameters informed by empirical data, we quantify the power to detect, among cases, a lower PB in LEV carriers than in non-carriers. Furthermore, we uncover clinically useful conditions wherein the risk derived from the PB is comparable to the LEV-derived risk. The resulting summary-statistics-based methodology (with publicly available software, PB-LEV-SCAN) makes predictions on PB-based LEV screening for 36 complex traits, which we confirm in several disease datasets with available LEV information in the UK Biobank, with important implications on clinical decision-making.
Miniature neurotransmission is required to maintain Drosophila synaptic structures during ageing
Authors: Banerjee Soumya , Vernon Samuel , Jiao Wei , Choi Ben Jiwon , Ruchti Evelyne , Asadzadeh Jamshid , Burri Olivier , Stowers R. Steven , McCabe Brian D. 
Published: July 2021

AbstractThe decline of neuronal synapses is an established feature of ageing accompanied by the diminishment of neuronal function, and in the motor system at least, a reduction of behavioural capacity. Here, we have investigated Drosophila motor neuron synaptic terminals during ageing. We observed cumulative fragmentation of presynaptic structures accompanied by diminishment of both evoked and miniature neurotransmission occurring in tandem with reduced motor ability. Through discrete manipulation of each neurotransmission modality, we find that miniature but not evoked neurotransmission is required to maintain presynaptic architecture and that increasing miniature events can both preserve synaptic structures and prolong motor ability during ageing. Our results establish that miniature neurotransmission, formerly viewed as an epiphenomenon, is necessary for the long-term stability of synaptic connections.
X-ray studies bridge the molecular and macro length scales during the emergence of CoO assemblies
Authors: Grote Lukas , Zito Cecilia A. , Frank Kilian , Dippel Ann-Christin , Reisbeck Patrick , Pitala Krzysztof , Kvashnina Kristina O. , Bauters Stephen , Detlefs Blanka , Ivashko Oleh , Pandit Pallavi , Rebber Matthias , Harouna-Mayer Sani Y. , Nickel Bert , Koziej Dorota 
Published: July 2021

AbstractThe key to fabricating complex, hierarchical materials is the control of chemical reactions at various length scales. To this end, the classical model of nucleation and growth fails to provide sufficient information. Here, we illustrate how modern X-ray spectroscopic and scattering in situ studies bridge the molecular- and macro- length scales for assemblies of polyhedrally shaped CoO nanocrystals. Utilizing high energy-resolution fluorescence-detected X-ray absorption spectroscopy, we directly access the molecular level of the nanomaterial synthesis. We reveal that initially Co(acac)3 rapidly reduces to square-planar Co(acac)2 and coordinates to two solvent molecules. Combining atomic pair distribution functions and small-angle X-ray scattering we observe that, unlike a classical nucleation and growth mechanism, nuclei as small as 2 nm assemble into superstructures of 20 nm. The individual nanoparticles and assemblies continue growing at a similar pace. The final spherical assemblies are smaller than 100 nm, while the nanoparticles reach a size of 6 nm and adopt various polyhedral, edgy shapes. Our work thus provides a comprehensive perspective on the emergence of nano-assemblies in solution.
Early-life social experience affects offspring DNA methylation and later life stress phenotype
Authors: Laubach Zachary M. , Greenberg Julia R. , Turner Julie W. , Montgomery Tracy M. , Pioon Malit O. , Sawdy Maggie A. , Smale Laura , Cavalcante Raymond G. , Padmanabhan Karthik R. , Lalancette Claudia , vonHoldt Bridgett , Faulk Christopher D. , Dolinoy Dana C. , Holekamp Kay E. , Perng Wei 
Published: July 2021

AbstractStudies in rodents and captive primates suggest that the early-life social environment affects future phenotype, potentially through alterations to DNA methylation. Little is known of these associations in wild animals. In a wild population of spotted hyenas, we test the hypothesis that maternal care during the first year of life and social connectedness during two periods of early development leads to differences in DNA methylation and fecal glucocorticoid metabolites (fGCMs) later in life. Here we report that although maternal care and social connectedness during the den-dependent life stage are not associated with fGCMs, greater social connectedness during the subadult den-independent life stage is associated with lower adult fGCMs. Additionally, more maternal care and social connectedness after den independence correspond with higher global (%CCGG) DNA methylation. We also note differential DNA methylation near 5 genes involved in inflammation, immune response, and aging that may link maternal care with stress phenotype.
TGFβ promotes fibrosis by MYST1-dependent epigenetic regulation of autophagy
Authors: Zehender Ariella , Li Yi-Nan , Lin Neng-Yu , Stefanica Adrian , Nüchel Julian , Chen Chih-Wei , Hsu Hsiao-Han , Zhu Honglin , Ding Xiao , Huang Jingang , Shen Lichong , Györfi Andrea-Hermina , Soare Alina , Rauber Simon , Bergmann Christina , Ramming Andreas , Plomann Markus , Eckes Beate , Schett Georg , Distler Jörg H. W. 
Published: July 2021

AbstractActivation of fibroblasts is essential for physiological tissue repair. Uncontrolled activation of fibroblasts, however, may lead to tissue fibrosis with organ dysfunction. Although several pathways capable of promoting fibroblast activation and tissue repair have been identified, their interplay in the context of chronic fibrotic diseases remains incompletely understood. Here, we provide evidence that transforming growth factor-β (TGFβ) activates autophagy by an epigenetic mechanism to amplify its profibrotic effects. TGFβ induces autophagy in fibrotic diseases by SMAD3-dependent downregulation of the H4K16 histone acetyltransferase MYST1, which regulates the expression of core components of the autophagy machinery such as ATG7 and BECLIN1. Activation of autophagy in fibroblasts promotes collagen release and is both, sufficient and required, to induce tissue fibrosis. Forced expression of MYST1 abrogates the stimulatory effects of TGFβ on autophagy and re-establishes the epigenetic control of autophagy in fibrotic conditions. Interference with the aberrant activation of autophagy inhibits TGFβ-induced fibroblast activation and ameliorates experimental dermal and pulmonary fibrosis. These findings link uncontrolled TGFβ signaling to aberrant autophagy and deregulated epigenetics in fibrotic diseases and may contribute to the development of therapeutic interventions in fibrotic diseases.
Comparative analysis of two paradigm bacteriophytochromes reveals opposite functionalities in two-component signaling
Authors: Multamäki Elina , Nanekar Rahul , Morozov Dmitry , Lievonen Topias , Golonka David , Wahlgren Weixiao Yuan , Stucki-Buchli Brigitte , Rossi Jari , Hytönen Vesa P. , Westenhoff Sebastian , Ihalainen Janne A. , Möglich Andreas , Takala Heikki 
Published: July 2021

AbstractBacterial phytochrome photoreceptors usually belong to two-component signaling systems which transmit environmental stimuli to a response regulator through a histidine kinase domain. Phytochromes switch between red light-absorbing and far-red light-absorbing states. Despite exhibiting extensive structural responses during this transition, the model bacteriophytochrome from Deinococcus radiodurans (DrBphP) lacks detectable kinase activity. Here, we resolve this long-standing conundrum by comparatively analyzing the interactions and output activities of DrBphP and a bacteriophytochrome from Agrobacterium fabrum (Agp1). Whereas Agp1 acts as a conventional histidine kinase, we identify DrBphP as a light-sensitive phosphatase. While Agp1 binds its cognate response regulator only transiently, DrBphP does so strongly, which is rationalized at the structural level. Our data pinpoint two key residues affecting the balance between kinase and phosphatase activities, which immediately bears on photoreception and two-component signaling. The opposing output activities in two highly similar bacteriophytochromes suggest the use of light-controllable histidine kinases and phosphatases for optogenetics.
Evidence for higher order topology in Bi and Bi0.92Sb0.08
Authors: Aggarwal Leena , Zhu Penghao , Hughes Taylor L. , Madhavan Vidya 
Published: July 2021

AbstractHigher order topological insulators (HOTIs) are a new class of topological materials which host protected states at the corners or hinges of a crystal. HOTIs provide an intriguing alternative platform for helical and chiral edge states and Majorana modes, but there are very few known materials in this class. Recent studies have proposed Bi as a potential HOTI, however, its topological classification is not yet well accepted. In this work, we show that the (110) facets of Bi and BiSb alloys can be used to unequivocally establish the topology of these systems. Bi and Bi0.92Sb0.08 (110) films were grown on silicon substrates using molecular beam epitaxy and studied by scanning tunneling spectroscopy. The surfaces manifest rectangular islands which show localized hinge states on three out of the four edges, consistent with the theory for the HOTI phase. This establishes Bi and Bi0.92Sb0.08 as HOTIs, and raises questions about the topological classification of the full family of BixSb1−x alloys.
The impact of site-specific digital histology signatures on deep learning model accuracy and bias
Authors: Howard Frederick M. , Dolezal James , Kochanny Sara , Schulte Jefree , Chen Heather , Heij Lara , Huo Dezheng , Nanda Rita , Olopade Olufunmilayo I. , Kather Jakob N. , Cipriani Nicole , Grossman Robert L. , Pearson Alexander T. 
Published: July 2021

AbstractThe Cancer Genome Atlas (TCGA) is one of the largest biorepositories of digital histology. Deep learning (DL) models have been trained on TCGA to predict numerous features directly from histology, including survival, gene expression patterns, and driver mutations. However, we demonstrate that these features vary substantially across tissue submitting sites in TCGA for over 3,000 patients with six cancer subtypes. Additionally, we show that histologic image differences between submitting sites can easily be identified with DL. Site detection remains possible despite commonly used color normalization and augmentation methods, and we quantify the image characteristics constituting this site-specific digital histology signature. We demonstrate that these site-specific signatures lead to biased accuracy for prediction of features including survival, genomic mutations, and tumor stage. Furthermore, ethnicity can also be inferred from site-specific signatures, which must be accounted for to ensure equitable application of DL. These site-specific signatures can lead to overoptimistic estimates of model performance, and we propose a quadratic programming method that abrogates this bias by ensuring models are not trained and validated on samples from the same site.