bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of the Substorm as a Manifestation of Convection Transient
Authors: Tanaka T. , Ebihara Y. , Watanabe M. , Den M. , Fujita S. , Kikuchi T. , Hashimoto K. K. , Kataoka R. 
Published: September 2021

AbstractWe reproduced the substorm by global simulation and analyzed the development of convection, shear, the dynamo, and the field‐aligned current (FAC) at the final stage of the growth phase. From these investigations, we show that the substorm is a manifestation of reconfiguration in global flow dynamics. Ionospheric convection can be understood from two aspects. One understanding is as the potential field generated by the FAC, and the other is as the projection of magnetospheric convection. In order for the two to coincide, the FAC must be transmitted together with the motion. As a consequence, the resulting convection must be continuous from the magnetosphere to the ionosphere. We see this connection from the drawing of shear to recognize that the substorm is the projection process of transient convection. In the growth phase, convective shear that causes the quiet arc and the Harang reversal (HR) occurs on the open/closed boundary along the surface of the plasma sheet with a continuous flow structure from the magnetosphere to the ionosphere. The onset starts from a more local flow that is induced by the near‐earth neutral line (NENL). A narrow shear commences from the NENL in the mid‐tail and extends to the ionosphere to replace growth phase shear. Along a closed magnetic field line connected to the NENL, direct penetration flow, squeezing flow, the near‐earth dynamo, release of the HR, and the onset FAC occur successively and consequently cause the ground onset. Such onset mechanism is quite different from the model adopting the current wedge.
Warming Trend in Antarctic Bottom Water in the Vema Channel in the South Atlantic
Authors: Campos Edmo J. D. , van Caspel Mathias C. , Zenk Walter , Morozov Eugene G. , Frey Dmitry I. , Piola Alberto R. , Meinen Christopher S. , Sato Olga T. , Perez Renellys C. , Dong Shenfu 
Published: September 2021

AbstractThe excess heat absorbed from the atmosphere has increased the temperature in the upper layers of the ocean (<2,000 m). In the abyss, infrequently repeated ship sections, deep Argo float measurements, and sparse moored observations have found signs of warming in the Southwest Atlantic, possibly linked to changes in the Weddell Sea. We present a new moored temperature time series sampled near the bottom in the Vema Channel, from February 2019 to August 2020. Together with historical data, the combined record confirms the warming of the abyssal waters, with an increase of 0.059°C in potential temperature between January 1991 and August 2020, embedded within intense high‐frequency variability. Moreover, the data suggest the possibility of an accelerated warming, with a change in the temperature trend from 0.0016°C yr−1, between the early 1990s and 2005, to 0.0026°C yr−1 afterwards.
Leveraging the Cell Ontology to classify unseen cell types
Authors: Wang Sheng , Pisco Angela Oliveira , McGeever Aaron , Brbic Maria , Zitnik Marinka , Darmanis Spyros , Leskovec Jure , Karkanias Jim , Altman Russ B. 
Published: September 2021

AbstractSingle cell technologies are rapidly generating large amounts of data that enables us to understand biological systems at single-cell resolution. However, joint analysis of datasets generated by independent labs remains challenging due to a lack of consistent terminology to describe cell types. Here, we present OnClass, an algorithm and accompanying software for automatically classifying cells into cell types that are part of the controlled vocabulary that forms the Cell Ontology. A key advantage of OnClass is its capability to classify cells into cell types not present in the training data because it uses the Cell Ontology graph to infer cell type relationships. Furthermore, OnClass can be used to identify marker genes for all the cell ontology categories, regardless of whether the cell types are present or absent in the training data, suggesting that OnClass goes beyond a simple annotation tool for single cell datasets, being the first algorithm capable to identify marker genes specific to all terms of the Cell Ontology and offering the possibility of refining the Cell Ontology using a data-centric approach.
Molecular correlates of response to eribulin and pembrolizumab in hormone receptor-positive metastatic breast cancer
Authors: Keenan Tanya E. , Guerriero Jennifer L. , Barroso-Sousa Romualdo , Li Tianyu , O’Meara Tess , Giobbie-Hurder Anita , Tayob Nabihah , Hu Jiani , Severgnini Mariano , Agudo Judith , Vaz-Luis Ines , Anderson Leilani , Attaya Victoria , Park Jihye , Conway Jake , He Meng Xiao , Reardon Brendan , Shannon Erin , Wulf Gerburg , Spring Laura M. , Jeselsohn Rinath , Krop Ian , Lin Nancy U. , Partridge Ann , Winer Eric P. , Mittendorf Elizabeth A. , Liu David , Van Allen Eliezer M. , Tolaney Sara M. 
Published: September 2021

AbstractImmune checkpoint inhibitors (ICIs) have minimal therapeutic effect in hormone receptor-positive (HR+ ) breast cancer. We present final overall survival (OS) results (n = 88) from a randomized phase 2 trial of eribulin ± pembrolizumab for patients with metastatic HR+ breast cancer, computationally dissect genomic and/or transcriptomic data from pre-treatment tumors (n = 52) for molecular associations with efficacy, and identify cytokine changes differentiating response and ICI-related toxicity (n = 58). Despite no improvement in OS with combination therapy (hazard ratio 0.95, 95% CI 0.59–1.55, p = 0.84), immune infiltration and antigen presentation distinguished responding tumors, while tumor heterogeneity and estrogen signaling independently associated with resistance. Moreover, patients with ICI-related toxicity had lower levels of immunoregulatory cytokines. Broadly, we establish a framework for ICI response in HR+ breast cancer that warrants diagnostic and therapeutic validation. ClinicalTrials.gov Registration: NCT03051659.
High-efficiency broadband achromatic metalens for near-IR biological imaging window
Authors: Wang Yujie , Chen Qinmiao , Yang Wenhong , Ji Ziheng , Jin Limin , Ma Xing , Song Qinghai , Boltasseva Alexandra , Han Jiecai , Shalaev Vladimir M. , Xiao Shumin 
Published: September 2021

AbstractOver the past years, broadband achromatic metalenses have been intensively studied due to their great potential for applications in consumer and industry products. Even though significant progress has been made, the efficiency of technologically relevant silicon metalenses is limited by the intrinsic material loss above the bandgap. In turn, the recently proposed achromatic metalens utilizing transparent, high-index materials such as titanium dioxide has been restricted by the small thickness and showed relatively low focusing efficiency at longer wavelengths. Consequently, metalens-based optical imaging in the biological transparency window has so far been severely limited. Herein, we experimentally demonstrate a polarization-insensitive, broadband titanium dioxide achromatic metalens for applications in the near-infrared biological imaging. A large-scale fabrication technology has been developed to produce titanium dioxide nanopillars with record-high aspect ratios featuring pillar heights of 1.5 µm and ~90° vertical sidewalls. The demonstrated metalens exhibits dramatically increased group delay range, and the spectral range of achromatism is substantially extended to the wavelength range of 650–1000 nm with an average efficiency of 77.1%–88.5% and a numerical aperture of 0.24–0.1. This research paves a solid step towards practical applications of flat photonics.
A Brewster route to Cherenkov detectors
Authors: Lin Xiao , Hu Hao , Easo Sajan , Yang Yi , Shen Yichen , Yin Kezhen , Blago Michele Piero , Kaminer Ido , Zhang Baile , Chen Hongsheng , Joannopoulos John , Soljačić Marin , Luo Yu 
Published: September 2021

AbstractCherenkov detectors enable a valuable tool to identify high-energy particles. However, their sensitivity and momentum coverage are limited by the refractive index of host materials. Especially, identifying particles with energy above multiple gigaelectronvolts requires host materials with a near-unity refractive index, which are limited to bulky gas chambers. Overcoming this fundamental material limit is important for future particle detectors yet remains a long-standing challenge. Here, we propose a different paradigm for Cherenkov detectors that utilizes the broadband angular filter made from stacks of variable one-dimensional photonic crystals. Owing to the Brewster effect, the angular filter is transparent only to Cherenkov photons from a precise incident angle. Particle identification is achieved by mapping each Cherenkov angle to the peak-intensity position of transmitted photons in the detection plane. Such angular filtering effect, although decreases the photon number collected in the detection plane, enables the realization of a non-dispersive pseudo refractive index over the entire visible spectrum. Moreover, the pseudo refractive index can be flexibly designed to different values close to unity. Our angular-selective Brewster paradigm offers a feasible solution to implement compact and highly sensitive Cherenkov detectors especially in beam lines with a small angular divergence using regular dielectrics.
Epistasis shapes the fitness landscape of an allosteric specificity switch
Authors: Nishikawa Kyle K. , Hoppe Nicholas , Smith Robert , Bingman Craig , Raman Srivatsan 
Published: September 2021

AbstractEpistasis is a major determinant in the emergence of novel protein function. In allosteric proteins, direct interactions between inducer-binding mutations propagate through the allosteric network, manifesting as epistasis at the level of biological function. Elucidating this relationship between local interactions and their global effects is essential to understanding evolution of allosteric proteins. We integrate computational design, structural and biophysical analysis to characterize the emergence of novel inducer specificity in an allosteric transcription factor. Adaptive landscapes of different inducers of the designed mutant show that a few strong epistatic interactions constrain the number of viable sequence pathways, revealing ridges in the fitness landscape leading to new specificity. The structure of the designed mutant shows that a striking change in inducer orientation still retains allosteric function. Comparing biophysical and functional properties suggests a nonlinear relationship between inducer binding affinity and allostery. Our results highlight the functional and evolutionary complexity of allosteric proteins.
Synthetic hydrogel nanoparticles for sepsis therapy
Authors: Koide Hiroyuki , Okishima Anna , Hoshino Yu , Kamon Yuri , Yoshimatsu Keiichi , Saito Kazuhiro , Yamauchi Ikumi , Ariizumi Saki , Zhou Yuqi , Xiao Ting-Hui , Goda Keisuke , Oku Naoto , Asai Tomohiro , Shea Kenneth J. 
Published: September 2021

AbstractSepsis is a life-threatening condition caused by the extreme release of inflammatory mediators into the blood in response to infection (e.g., bacterial infection, COVID-19), resulting in the dysfunction of multiple organs. Currently, there is no direct treatment for sepsis. Here we report an abiotic hydrogel nanoparticle (HNP) as a potential therapeutic agent for late-stage sepsis. The HNP captures and neutralizes all variants of histones, a major inflammatory mediator released during sepsis. The highly optimized HNP has high capacity and long-term circulation capability for the selective sequestration and neutralization of histones. Intravenous injection of the HNP protects mice against a lethal dose of histones through the inhibition of platelet aggregation and migration into the lungs. In vivo administration in murine sepsis model mice results in near complete survival. These results establish the potential for synthetic, nonbiological polymer hydrogel sequestrants as a new intervention strategy for sepsis therapy and adds to our understanding of the importance of histones to this condition.
Reconstructing aspects of human embryogenesis with pluripotent stem cells
Authors: Sozen Berna , Jorgensen Victoria , Weatherbee Bailey A. T. , Chen Sisi , Zhu Meng , Zernicka-Goetz Magdalena 
Published: September 2021

AbstractUnderstanding human development is of fundamental biological and clinical importance. Despite its significance, mechanisms behind human embryogenesis remain largely unknown. Here, we attempt to model human early embryo development with expanded pluripotent stem cells (EPSCs) in 3-dimensions. We define a protocol that allows us to generate self-organizing cystic structures from human EPSCs that display some hallmarks of human early embryogenesis. These structures mimic polarization and cavitation characteristic of pre-implantation development leading to blastocyst morphology formation and the transition to post-implantation-like organization upon extended culture. Single-cell RNA sequencing of these structures reveals subsets of cells bearing some resemblance to epiblast, hypoblast and trophectoderm lineages. Nevertheless, significant divergences from natural blastocysts persist in some key markers, and signalling pathways point towards ways in which morphology and transcriptional-level cell identities may diverge in stem cell models of the embryo. Thus, this stem cell platform provides insights into the design of stem cell models of embryogenesis.
SON drives oncogenic RNA splicing in glioblastoma by regulating PTBP1/PTBP2 switching and RBFOX2 activity
Authors: Kim Jung-Hyun , Jeong Kyuho , Li Jianfeng , Murphy James M. , Vukadin Lana , Stone Joshua K. , Richard Alexander , Tran Johnny , Gillespie G. Yancey , Flemington Erik K. , Sobol Robert W. , Lim Ssang-Teak Steve , Ahn Eun-Young Erin 
Published: September 2021

AbstractWhile dysregulation of RNA splicing has been recognized as an emerging target for cancer therapy, the functional significance of RNA splicing and individual splicing factors in brain tumors is poorly understood. Here, we identify SON as a master regulator that activates PTBP1-mediated oncogenic splicing while suppressing RBFOX2-mediated non-oncogenic neuronal splicing in glioblastoma multiforme (GBM). SON is overexpressed in GBM patients and SON knockdown causes failure in intron removal from the PTBP1 transcript, resulting in PTBP1 downregulation and inhibition of its downstream oncogenic splicing. Furthermore, SON forms a complex with hnRNP A2B1 and antagonizes RBFOX2, which leads to skipping of RBFOX2-targeted cassette exons, including the PTBP2 neuronal exon. SON knockdown inhibits proliferation and clonogenicity of GBM cells in vitro and significantly suppresses tumor growth in orthotopic xenografts in vivo. Collectively, our study reveals that SON-mediated RNA splicing is a GBM vulnerability, implicating SON as a potential therapeutic target in brain tumors.
FDG positron emission tomography imaging and ctDNA detection as an early dynamic biomarker of everolimus efficacy in advanced luminal breast cancer
Authors: Gombos Andrea , Venet David , Ameye Lieveke , Vuylsteke Peter , Neven Patrick , Richard Vincent , Duhoux Francois P. , Laes Jean-Francois , Rothe Françoise , Sotiriou Christos , Paesmans Marianne , Awada Ahmad , Guiot Thomas , Flamen Patrick , Piccart-Gebhart Martine , Ignatiadis Michail , Gebhart Géraldine 
Published: September 2021

AbstractBiomarkers to identify patients without benefit from adding everolimus to endocrine treatment in metastatic breast cancer (MBC) are needed. We report the results of the Pearl trial conducted in five Belgian centers assessing 18F-FDG-PET/CT non-response (n = 45) and ctDNA detection (n = 46) after 14 days of exemestane-everolimus (EXE-EVE) to identify MBC patients who will not benefit. The metabolic non-response rate was 66.6%. Median PFS in non-responding patients (using as cut-off 25% for SUVmax decrease) was 3.1 months compared to 6.0 months in those showing response (HR: 0.77, 95% CI: 0.40–1.50, p = 0.44). The difference was significant when using a “post-hoc” cut-off of 15% (PFS 2.2 months vs 6.4 months). ctDNA detection at D14 was associated with PFS: 2.1 months vs 5.0 months (HR-2.5, 95% CI: 1.3–5.0, p = 0.012). Detection of ctDNA and/or the absence of 18F-FDG-PET/CT response after 14 days of EXE-EVE identifies patients with a low probability of benefiting from treatment. Independent validation is needed.
Electronic structure and signature of Tomonaga–Luttinger liquid state in epitaxial CoSb1−x nanoribbons
Authors: Lou Rui , Lei Minyinan , Ding Wenjun , Yang Wentao , Chen Xiaoyang , Tao Ran , Ding Shuyue , Shen Xiaoping , Yan Yajun , Cui Ping , Xu Haichao , Peng Rui , Zhang Tong , Zhang Zhenyu , Feng Donglai 
Published: September 2021

AbstractRecently, monolayer CoSb/SrTiO3 has been proposed as a candidate harboring interfacial superconductivity in analogy with monolayer FeSe/SrTiO3. Experimentally, while the CoSb-based compounds manifesting as nanowires and thin films have been realized on SrTiO3 substrates, serving as a rich playground, their electronic structures are still unknown and yet to be resolved. Here, we have fabricated CoSb1−x nanoribbons with quasi-one-dimensional stripes on SrTiO3(001) substrates using molecular beam epitaxy and investigated the electronic structure by in situ angle-resolved photoemission spectroscopy. Straight Fermi surfaces without lateral dispersions are observed. CoSb1−x/SrTiO3 is slightly hole doped, where the interfacial charge transfer is opposite to that in monolayer FeSe/SrTiO3. The spectral weight near the Fermi level exhibits power-law-like suppression and obeys a universal temperature scaling, serving as the signature of Tomonaga–Luttinger liquid (TLL) state. The obtained TLL parameter of ~0.21 shows the underlying strong correlations. Our results not only suggest CoSb1−x nanoribbon as a representative TLL system but also provide clues for further investigations on the CoSb-related interface.
Origin of pyrite nodules at the top of the nantuo diamictites, Southern China
Authors: Liu Changjie , Lin Ying 
Published: September 2021

AbstractPyrite nodules up to 20 cm in diameter are found at the top of the Marinoan (~ 635 Ma) Nantuo glacial diamictite as well as in the cap dolostones and shale/siltstones in the lower Doushantuo Formation in eastern Guizhou, southern China. Field occurrences, petrography, and stable sulfur isotopic compositions of pyrite nodules were studied from a section at Taoying, eastern Guizhou, China. Pyrite δ34S values from different nodules varied from 7.3 to 60.5‰ at different stratigraphic levels. No stratigraphic trend existed for the δ34S, supporting the scenario of pyrite formation in sediments before the precipitation of the cap dolostone. Pyrite δ34S values were also homogeneous within individual nodules at a 0.3 to 1 cm sampling scale, but were more heterogeneous at a 2 mm sampling scale. Homogeneity was not expected from the particular model for pyrite nodule formation in a largely closed or semi-closed environment. Thus, differential cementation and compaction of the pyrite-bearing sediments may have produced the nodular shape of the pyrite deposit.
Exploring reward-related attention selectivity deficits in Parkinson’s disease
Authors: Pilgrim Matthew J. D. , Ou Zhen-Yi Andy , Sharp Madeleine 
Published: September 2021

AbstractAn important aspect of managing a limited cognitive resource like attention is to use the reward value of stimuli to prioritize the allocation of attention to higher-value over lower-value stimuli. Recent evidence suggests this depends on dopaminergic signaling of reward. In Parkinson’s disease, both reward sensitivity and attention are impaired, but whether these deficits are directly related to one another is unknown. We tested whether Parkinson’s patients use reward information when automatically allocating their attention and whether this is modulated by dopamine replacement. We compared patients, tested both ON and OFF dopamine replacement medication, to older controls using a standard attention capture task. First, participants learned the different reward values of stimuli. Then, these reward-associated stimuli were used as distractors in a visual search task. We found that patients were generally distracted by the presence of the distractors but that the degree of distraction caused by the high-value and low-value distractors was similar. Furthermore, we found no evidence to support the possibility that dopamine replacement modulates the effect of reward on automatic attention allocation. Our results suggest a possible inability in Parkinson’s patients to use the reward value of stimuli when automatically allocating their attention, and raise the possibility that reward-driven allocation of resources may affect the adaptive modulation of other cognitive processes.
A direct aircraft observation of helical rolls in the tropical cyclone boundary layer
Authors: Tang Jie , Zhang Jun A. , Chan Pakwai , Hon Kaikwong , Lei Xiaotu , Wang Yuan 
Published: September 2021

AbstractHelical rolls are known to play a significant role in modulating both the mean and turbulence structure of the atmospheric boundary layer in tropical cyclones. However, in-situ measurements of these rolls have been limited due to safety restrictions. This study presents analyses of data collected by an aircraft operated by the Hong Kong Observatory in Typhoon Kalmaegi (1415) and Typhoon Nida (1604). Examination of the flight-level data at ~ 600 m altitude confirmed the existence of sub-kilometer-scale rolls. These rolls were mostly observed in the outer-core region. Turbulent momentum fluxes were computed using the eddy correlation method. The averaged momentum flux of flight legs with rolls was found to be ~ 2.5 times that of legs without rolls at a similar wind speed range. This result suggests that rolls could significantly modulate turbulent transfer in the tropical cyclone boundary layer. This roll effect on turbulent fluxes should be considered in the planetary boundary layer parameterization schemes of numerical models simulating and forecasting tropical cyclones.