bluuebunny/crossref_metadata_2025 huggingface dataset:
Immune system and angiogenesis-related potential surrogate biomarkers of response to everolimus-based treatment in hormone receptor-positive breast cancer: an exploratory study
Authors: Schettini Francesco , Sobhani Navid , Ianza Anna , Triulzi Tiziana , Molteni Alfredo , Lazzari Maria Chiara , Strina Carla , Milani Manuela , Corona Silvia Paola , Sirico Marianna , Bernocchi Ottavia , Giudici Fabiola , Cappelletti Maria Rosaria , Ciruelos Eva , Jerusalem Guy , Loi Sherine , Fox Stephen B. , Generali Daniele
Published: August 2020

Purpose

mTOR inhibitor everolimus is used for hormone receptor-positive (HR+)/HER2-negative metastatic breast cancer (mBC). No reliable predictive biomarker of response is available. Following evidences from other solid tumors, we aimed to assess the association between treatment-associated immune system features and everolimus activity.

Methods

We retrospectively explored a correlation with the therapeutic activity of everolimus and tumor-associated immune pathways with ingenuity pathway analysis (IPA), neutrophil-to-lymphocyte ratio (NLR), circulating lymphocytes, and endothelial cells (CECs) in 3 different HR+ mBC studies, including the BALLET phase IIIb study.

Results

The circulating levels of CD3+/CD8+, CD3+/CD4+, and overall T lymphocytes were higher in responders versus non-responders at baseline (p = 0.017, p < 0.001, p = 0.034) and after treatment (p = 0.01, p = 0.003, p = 0.023). Reduced CECs, a tumor neoangiogenesis marker, were observed in responders after treatment (p < 0.001). Patients with low NLR (≤ 4.4) showed a better progression-free survival compared to patients with high NLR (> 4.4) (p = 0.01). IPA showed that the majority of immunity-related genes were found upregulated in responders compared to non-responders before treatment, but not after.

Conclusions

Lymphocytes subpopulations, CECs and NLR could be interesting biomarkers predictive of response to everolimus-based regimens, potentially useful in daily clinical practice to select/monitor everolimus-based treatment in mBC. Further studies to confirm such hypotheses are warranted.
Convex plumbings in closed hyperbolic 4-manifolds
Authors: Martelli Bruno , Riolo Stefano , Slavich Leone
Published: August 2020

We show that every plumbing of disc bundles over surfaces whose genera satisfy a simple inequality may be embedded as a convex submanifold in some closed hyperbolic four-manifold. In particular its interior has a geometrically finite hyperbolic structure that covers a closed hyperbolic four-manifold.
Children’s interactions with technology in teachers’ self-reported activities in Sweden’s preschools
Authors: Nilsson Tor , Gustafsson Peter , Sundqvist Pernilla
Published: August 2020

This study investigates preschool children’s interactions with technology in a Swedish context. The purpose is to broaden our knowledge about children, technology and preschool activities—not only the meanings of technology that is present in everyday preschool activities, but also how children interact with it. Collier-Reed’s (Pupils’ experiences of technology: exploring dimensions of technological literacy, PhD thesis, University of Cape Town, Cape Town, 2006) category system has been used to analyse data generated in two research circles. The participating preschool teachers were asked to present teacher- and children-initiated activities from their daily practices. 54 cases were identified, of which 40 included children’s interactions with technology according to the definitions provided by Collier-Reed. Mapping the results in a matrix representation based on Collier-Reed’s two sets of categorisation systems shows two clusters. The first mainly includes teacher-initiated activities, in which children were instructed how to use different artefacts. The second also includes children-initiated activities requiring more engagement as part of Collier-Reed’s notion of thecore. Also,labellingwas added to the category system in order to adapt it to the Swedish preschool setting.
Spatial patterns of logging-related disturbance events: a multi-scale analysis on forest management units located in the Brazilian Amazon
Authors: Lima Thaís Almeida , Beuchle René , Griess Verena C. , Verhegghen Astrid , Vogt Peter
Published: August 2020

Context

Selective logging has been commonly mapped using binary maps, representing logged and unlogged forests. However, binary maps may fall short regarding the optimum representation of this type of disturbance, as tree harvest in tropical forests can be highly heterogeneous.

Objectives

The objective of this study is to map forest disturbance intensities in areas of selective logging located in the Brazilian Amazon.

Methods

Selective logging activities were mapped in ten forest management units using Sentinel-2 data at 10 m resolution. A spatial pattern analysis was applied to the logging map, using a moving window approach with different window sizes. Two landscape metrics were used to derive a forest disturbance intensity map. This map was then compared with actual disturbances using field data and a post-harvest forest recovery analysis.

Results

Disturbed areas were grouped into five distinct disturbance intensity classes, from very low to very high. Classes high and very high were found to be related to log landings and large felling gaps, while very low intensities were mainly related to isolated disturbance types. The post-harvest forest recovery analysis showed that the five classes can be clearly distinguished from one another, with the clearest differences in the year of logging and one year after it.

Conclusions

The approach described represents an important step towards a better mapping of selectively logged areas, when compared to the use of binary maps. The disturbance intensity classes could be used as indicators for forest monitoring as well as for further evaluation of areas under forest management.
Road Traffic and Aircraft Noise as Drivers of Environmental Protest?
Authors: Preisendörfer Peter , Herold Lucie , Kurz Karin
Published: August 2020

This article investigates whether and to what extent unfavorable local environmental conditions furnish an important motivator for environmental protest. We do so using individual-level data on objective and subjectively perceived residential road traffic and aircraft noise pollution, pertaining to the cities of Mainz (Germany) and Zurich (Switzerland). By referring to fine-grained noise data, we are able to test the predictive power of grievances and self-interest in explaining protest participation more stringently than has been the case in most previous studies. Theoretically, our study is inspired by Klandermans’ socio-psychological framework of political protest, the pressure-response approach, the self-interest perspective, and the collective-interest model. Our empirical findings only partially confirm the grievances assumption that unfavorable local environmental conditions in the form of residential road traffic and aircraft noise stimulate environmental protest. Noise caused by airplanes seems to be more “protest-inducing” than that produced by road traffic. It is not so much the objectively measurable noise level as its subjective perception and evaluation that are deciding factors. However, in line with Klandermans’ protest framework and other theories of political protest, there are more influential drivers of environmental protest, such as environmental concerns and a left-wing political ideology. Thus, the effects of residential road traffic and aircraft noise turn out to be relatively moderate. Ultimately, this means that our tailored measures of grievances corroborate a relatively well-established finding of protest research.
Optimal Transport on Completely Integrable Toric Manifolds
Authors: Myga Szymon
Published: August 2020

Following the work of Berman and Witt Nyström we present the proof of existence and uniqueness of solutions to transported Monge–Ampère problem on complex compact manifolds with completely integrable torus action. The proof is based on the real theory of optimal transportation and some convex analysis.
Physico-chemical structure evolution characteristics of coal char during gasification in the presence of iron-based waste catalyst
Authors: Zhang Xinsha , Song Xudong , Wang Jiaofei , Su Weiguang , Zhou Bing , Bai Yonghui , Yu Guangsuo
Published: August 2020

The present study aims to explore the physico-chemical structure evolution characteristic during Yangchangwan bituminous coal (YCW) gasification in the presence of iron-based waste catalyst (IWC). The catalytic gasification reactivity of YCW was measured by thermogravimetric analyzer. Scanning electron microscope–energy dispersive system, nitrogen adsorption analyzer and laser Raman spectroscopy were employed to analyze the char physico-chemical properties. The results show that the optimal IWC loading ratio was 5 wt% at 1000 °C. The distribution of IWC on char was uneven and Fe catalyst concentrated on the surface of some chars. The specific surface area of YCW gasified semi-char decreased significantly with the increase of gasification time. i.e., the specific surface area reduced from 382 m2/g (0 min) to 192 m2/g (3 min), meanwhile, the number of micropores and mesopores decreased sharply at the late gasification stage. The carbon microcrystalline structure of YCW gasified semi-char was gradually destroyed with the increase of gasification time, and the microcrystalline structure with small size was gradually generated, resulting in the decreasing order degree of carbon microcrystalline structure. IWC can catalyze YCW gasification which could provide theoretical guidance for industrial solid waste recycling.
Suppressing Li Dendrites via Electrolyte Engineering by Crown Ethers for Lithium Metal Batteries
Authors: Zhang Shanqing
Published: August 2020

Electrolyte engineering is considered as an effective strategy to establish stable solid electrolyte interface (SEI), and thus to suppress the growth of lithium dendrites. In a recent study reported in Advanced Functional Materials by Ma group, discovered that strong coordination force could be founded between 15-Crown-5 ether (15-C-5) and Li+, which facilitates the crown ether (15-C-1) to participate in the solvation structure of Li+ in the electrolyte for the same purpose. Such a novel strategy might impact the design of high-performance and safe lithium metal batteries (LMBs).
Flipped Classroom Approach Used in the Training of Mass Casualty Triage for Medical Undergraduate Students
Authors: Zheng Ziyu , Yuan Shiwen , Huang Mingcheng , Liao Jinli , Cai Ruibin , Zhan Hong , Yang Zhen , Xiong Yan
Published: August 2020

Objective:

The aim of this study was to explore the application of the flipped classroom approach in the training of Mass Casualty Triage (MCT) to medical undergraduate students.

Methods:

In this study, 103 fourth-year medical students were randomly divided into a Flipped Classroom (FC) group (n = 51) and a Traditional Lecture-based Classroom (TLC) group (n = 52). A post-class quiz, simulated field triage (SFT) and feedback questionnaires were performed to assess both groups of students for their learning of the course.

Results:

In the post-quiz, the median (IQR) scores achieved by students from the FC and TLC groups were 42(5) and 39(5.5), respectively. Significant differences were found between the two groups. In the SFT, overall triage accuracy was 67.06% for FC, and 64.23% for TLC students. Over-triage and under-triage errors occurred in 18.43% and 14.50% of the FC group, respectively. The TLC group had a similar pattern of 20.77% over-triage and 15.0% under-triage errors. No significant differences were found regarding overall triage accuracy or triage errors between the two groups.

Conclusions:

The FC approach could enhance course grades reflected in the post-quiz and improve students’ satisfaction with the class. However, there was no significant difference of competency between the two groups demonstrated in the SFT exercise.
Beyond modal idioms and modal harmony: a corpus-based analysis of gradient idiomaticity inmod+advcollocations
Authors: FLACH SUSANNE
Published: August 2020

How do we know thatwould ratherandmay wellare more idiomatic thanwould wellorwill really? Can this intuition be measured systematically in usage data? Traditionally, modal idioms suchhad/’d better,would/’d ratherormight (as) wellare seen as distinct from more compositional collocations, which may be modally harmonic (could possibly,will probably) or not (could also,might even). Yet the collocation of modal auxiliaries + adverbs (mod + adv)is more complex than suggested by a binary classification into idioms and non-idioms. This article uses data from COCA and the method of collostructional analysis to show that the difference between qualitatively distinct types ofmod + advis a matter of degree. Modal idiomaticity should be seen as gradient along a continuum from strong association (would rather) to strong dissociation (would well). The results support assumptions that statistical information about the collocational behavior of modal auxiliaries is a cue for the scope of adverbial modification and is thus an important aspect of speakers’ knowledge of modal meaning. The study contributes to recent approaches to modality from a ‘combinatorial’ perspective, which recognizes the importance of the lexical environment in core areas of grammar.
Power, luck, and scholarly responsibility at the end of the world(s)
Authors: Pelopidas Benoît
Published: August 2020

This contribution argues that the concept of protean power opens a space to think about the limits of control and knowledge about catastrophic possibilities such as nuclear war. To do so, it offers the first distinctive definition of nuclear luck, which has long been acknowledged by policy and military leaders but remains unaccounted for in scholarship. It further shows that the nuclear realm is defined by two key unknowables. However, it argues that protean power perpetuates a survivability bias which has characterized scholarship so far, before suggesting ways to overcome that bias and modify scholarly ethos to acknowledge such catastrophic possibilities.
International law as a common language across spheres of authority?
Authors: BIRKENKÖTTER HANNAH
Published: August 2020

When actors express conflicting views about the validity or scope of norms or rules in relation to other norms or rules in the international sphere, they often do so in the language of international law. This contribution argues that international law’s hermeneutic acts as a common language that cuts across spheres of authority and can thus serve as a conflict management tool for interface conflicts. Often, this entails resorting to an international court. While acknowledging that courts cannot provide permanent solutions to the underlying political conflict, I submit that court proceedings are interesting objects of study that promote our understanding of how international legal argument operates as a conflict management device. I distinguish three dimensions of common legal form, using the well-knownEC–Hormonescase as illustration: a procedural, argumentative, and substantive dimension. While previous scholarship has often focused exclusively on the substantive dimension, I argue that the other two dimensions are equally important. In concluding, I reflect on a possible explanation as to why actors are disposed to resort to international legal argument even if this is unlikely to result in a final solution: there is a specific authority claim attached to international law qua law.
Semiautomated Identification and Characterization of Dunes at Hargraves Crater, Mars
Authors: Emran A. , Marzen L. J. , King D. T.
Published: August 2020

The Mars Global Digital Dune Database (MGD3) contains information on Martian dune fields and prepared manually from the Thermal Emission Imaging System (THEMIS; 100 m/pixel) images. Although the MGD3 outlines dune fields, it overlooks the recognition of smaller dune forms. This paper aims to identify individual dunes from a semiautomated object‐based image analysis technique and characterize dune materials at Hargraves crater, Mars. MGD3 would benefit to be updated for an improved understanding of the Martian surface and its atmospheric mechanisms at a local scale. An object‐based image analysis technique was applied here to the Context Camera (CTX; 6 m/pixel) data set to extract dune data in a more efficient, reliable, and accurate fashion. This study is a test case in validating a remote sensing method that has wide applicability to the entire Martian surface resulting in an update to the dune database at a higher spatial resolution—providing a better understanding of surface and atmospheric behavior of Mars at the local scale. We also explored the wind flow and dune stability—presenting an insight into the dune modification mechanism—within the crater. The prevailing wind inside the crater flows to the west‐northwest. The dunes are labeled as active (stability index of 2) and do not appear to have been influenced by subsurface water ice or volatiles. We emphasize that the technique used here has a wide prospect in temporal monitoring of dune sediment flux, dune migration or erosion rates, improving near‐surface airflow modeling, and dune stability analysis.
Shallow Gas Hydrate Accumulations at a Nigerian Deepwater Pockmark—Quantities and Dynamics
Authors: Pape Thomas , Ruffine Livio , Hong Wei‐Li , Sultan Nabil , Riboulot Vincent , Peters Carl A. , Kölling Martin , Zabel Matthias , Garziglia Sébastien , Bohrmann Gerhard
Published: August 2020

The evolution of submarine pockmarks is often related to the ascent of fluid from the subsurface. For pockmarks located within the gas hydrate stability zone, methane oversaturation can result in the formation of gas hydrates in the sediment. An ~600 m‐wide sea floor depression in deep waters offshore Nigeria, Pockmark A, was investigated for distributions and quantities of shallow gas hydrates, origins of hydrocarbons, and time elapsed since the last major fluid ascent event. For the first time, pressure coring of shallow sediments and drilling of more than 50 m‐long cores with the sea floor drill rig MARUM‐MeBo70 were conducted in this pockmark. Unusually, high hydrate saturations of up to 51% of pore volume in the uppermost 2.5 m of sediment in the pockmark center substantiate that deepwater pockmarks are a relevant methane reservoir. Molecular and stable C and H isotopic compositions suggest that thermogenic hydrocarbons and secondary microbial methane resulting from petroleum biodegradation are injected into shallower sediments and mixed with primary microbial hydrocarbons. Two independent pore water chloride and sulfate modeling approaches suggest that a major methane migration event occurred during the past one to three centuries. A rough sea floor topography within the pockmark most likely results from combined sediment removal through ascending gas bubbles, hydrate clogging and deflection of migration pathways, gas pressure build‐up, and hydrate sea floor detachment. This study shows for the first time the chronological interrelationship between gas migration events, hydrate formation, and sea floor shaping in a deep sea pockmark.
The Norwegian‐Greenland Sea, the Laschamps, and the Mono Lake Excursions Recorded in a Black Sea Sedimentary Sequence Spanning From 68.9 to 14.5 ka
Authors: Liu Jiabo , Nowaczyk Norbert R. , Panovska Sanja , Korte Monika , Arz Helge W.
Published: August 2020

A full‐vector paleomagnetic record, comprising directional data and relative paleointensity (rPI), was derived from 16 sediment cores recovered from the southeastern Black Sea. The obtained data were used to create a stack covering the time window between 68.9 and 14.5 ka. Age models are based on radiocarbon dating and correlations of warming/cooling cycles monitored by high‐resolution X‐ray fluorescence (XRF) elementary ratios and by ice‐rafted debris (IRD) in Black Sea sediments to the sequence of “Dansgaard‐Oeschger” (D‐O) events defined from the Greenland ice core oxygen isotope stratigraphy. The reconstructed prominent lows in paleointensity at about 64.5, 41.2, and 34.5 ka are coeval with the Norwegian‐Greenland Sea, the Laschamps, and the Mono Lake excursions, respectively. For a further analysis, the stacked Black Sea paleomagnetic record was converted into one component being parallel to the direction expected from a geocentric axial dipole (GAD) and two components perpendicular to it (EW, inclined NS), representing definitely only non‐GAD components of the geomagnetic field. Discussions of the field configurations at the Black Sea site are focused on the three excursional events. The Norwegian‐Greenland Sea excursion was dominated by a decaying axial dipole and persisting weak nondipole field, with directional variations still within the range of normal secular variations. The Laschamps excursion comprises two full polarity transitions and a short stable interval of reversed polarity in between. The Mono Lake excursion was mostly dominated by a nondipole field, though with a less pronounced weakening of the axial dipole component.
A Lagrangian Snow‐Evolution System for Sea‐Ice Applications (SnowModel‐LG): Part I—Model Description
Authors: Liston Glen E. , Itkin Polona , Stroeve Julienne , Tschudi Mark , Stewart J. Scott , Pedersen Stine H. , Reinking Adele K. , Elder Kelly
Published: August 2020

A Lagrangian snow‐evolution model (SnowModel‐LG) was used to produce daily, pan‐Arctic, snow‐on‐sea‐ice, snow property distributions on a 25 × 25‐km grid, from 1 August 1980 through 31 July 2018 (38 years). The model was forced with NASA's Modern Era Retrospective‐Analysis for Research and Applications‐Version 2 (MERRA‐2) and European Centre for Medium‐Range Weather Forecasts (ECMWF) ReAnalysis‐5th Generation (ERA5) atmospheric reanalyses, and National Snow and Ice Data Center (NSIDC) sea ice parcel concentration and trajectory data sets (approximately 61,000, 14 × 14‐km parcels). The simulations performed full surface and internal energy and mass balances within a multilayer snowpack evolution system. Processes and features accounted for included rainfall, snowfall, sublimation from static‐surfaces and blowing‐snow, snow melt, snow density evolution, snow temperature profiles, energy and mass transfers within the snowpack, superimposed ice, and ice dynamics. The simulations produced horizontal snow spatial structures that likely exist in the natural system but have not been revealed in previous studies spanning these spatial and temporal domains. Blowing‐snow sublimation made a significant contribution to the snowpack mass budget. The superimposed ice layer was minimal and decreased over the last four decades. Snow carryover to the next accumulation season was minimal and sensitive to the melt‐season atmospheric forcing (e.g., the average summer melt period was 3 weeks or 50% longer with ERA5 forcing than MERRA‐2 forcing). Observed ice dynamics controlled the ice parcel age (in days), and ice age exerted a first‐order control on snow property evolution.
Contrasting Upper and Deep Ocean Oxygen Response to Protracted Global Warming
Authors: Frölicher T. L. , Aschwanden M. T. , Gruber N. , Jaccard S. L. , Dunne J. P. , Paynter D.
Published: August 2020

It is well established that the ocean is currently losing dissolved oxygen (O2) in response to ocean warming, but the long‐term, equilibrium response of O2 to a warmer climate is neither well quantified nor understood. Here we use idealized multimillennial global warming simulations with a comprehensive Earth system model to show that the equilibrium response in ocean O2 differs fundamentally from the ongoing transient response. After physical equilibration of the model (>4,000 years) under a two times preindustrial CO2 scenario, the deep ocean is better ventilated and oxygenated compared to preindustrial conditions, even though the deep ocean is substantially warmer. The recovery and overshoot of deep convection in the Weddell Sea and especially the Ross Sea after ~720 years causes a strong increase in deep ocean O2 that overcompensates the solubility‐driven decrease in O2. In contrast, O2 in most of the upper tropical ocean is substantially depleted owing to the warming‐induced O2 decrease dominating over changes in ventilation and biology. Our results emphasize the millennial‐scale impact of global warming on marine life, with some impacts emerging many centuries or even millennia after atmospheric CO2 has stabilized.
Wave‐Particle Interactions Associated With Io's Auroral Footprint: Evidence of Alfvén, Ion Cyclotron, and Whistler Modes
Authors: Sulaiman A. H. , Hospodarsky G. B. , Elliott S. S. , Kurth W. S. , Gurnett D. A. , Imai M. , Allegrini F. , Bonfond B. , Clark G. , Connerney J. E. P. , Ebert R. W. , Gershman D. J. , Hue V. , Janser S. , Kotsiaros S. , Paranicas C. , Santolík O. , Saur J. , Szalay J. R. , Bolton S. J.
Published: August 2020

The electrodynamic coupling between Io and Jupiter gives rise to wave‐particle interactions across multiple spatial scales. Here we report observations during Juno's 12th perijove (PJ) high‐latitude northern crossing of the flux tube connected to Io's auroral footprint. We focus on plasma wave measurements, clearly differentiating between magnetohydrodynamic (MHD), ion, and electron scales. We find (i) evidence of Alfvén waves undergoing a turbulent cascade, suggesting Alfvénic acceleration processes together with observations of bi‐directional, broadband electrons; (ii) intense ion cyclotron waves with an estimated heating rate that is consistent with the generation of ion conics reported by Clark et al. (2020, https://doi.org/10.1029/2020GL090839); and (iii) whistler‐mode auroral hiss radiation excited by field‐aligned electrons. Such high‐resolution wave and particle measurements provide an insight into satellite interactions in unprecedented detail. We further anticipate that these spatially well‐constrained results can be more broadly applied to better understand processes of Jupiter's main auroral oval.
Marine Heatwaves in the Arctic Region: Variation in Different Ice Covers
Authors: Hu Siyu , Zhang Lujun , Qian Shimeng
Published: August 2020

This study analyzes marine heatwaves (MHWs) in the Arctic for its variation in multiyear ice (MYI), first‐year ice (FYI), and open‐water areas. Results show that there is a significant annual growth in MHW frequency, duration, and intensity in the FYI region, especially for intensity. Since 2005, MHW in FYI increases remarkably in summer and the extent of the affected area continues to grow northward. Particularly, severe MHW events mainly occur in the area where sea ice concentration ranges between 0.1 and 0.5. Stratification in the FYI area impedes the deep mixing and downward transmission of energy from solar radiation, resulting in an anomalously high sea surface temperature in the FYI area. The implication is that MHW will keep growing as the extent of FYI in the Arctic increases.
City‐Scale Dark Fiber DAS Measurements of Infrastructure Use During the COVID‐19 Pandemic
Authors: Lindsey Nathaniel J. , Yuan Siyuan , Lellouch Ariel , Gualtieri Lucia , Lecocq Thomas , Biondi Biondo
Published: August 2020

Throughout the recent COVID‐19 pandemic, real‐time measurements about shifting use of roads, hospitals, grocery stores, and other public infrastructure became vital for government decision makers. Mobile phone locations are increasingly assimilated for this purpose, but an alternative, unexplored, natively anonymous, absolute method would be to use geophysical sensing to directly measure public infrastructure usage. In this paper, we demonstrate how fiber‐optic distributed acoustic sensing (DAS) connected to a telecommunication cable beneath Palo Alto, CA, successfully monitored traffic over a 2‐month period, including major reductions associated with COVID‐19 response. Continuous DAS recordings of over 450,000 individual vehicles were analyzed using an automatic template‐matching detection algorithm based on roadbed strain. In one commuter sector, we found a 50% decrease in vehicles immediately following the order, but near Stanford Hospital, the traffic persisted. The DAS measurements correlate with mobile phone locations and urban seismic noise levels, suggesting geophysics would complement future digital city sensing systems.
Daily and Monthly Variations of the Equatorial Ionization Anomaly (EIA) Over the Brazilian Sector During the Descending Phase of the Solar Cycle 24
Authors: Dias M. A. L. , Fagundes P. R. , Venkatesh K. , Pillat V. G. , Ribeiro B. A. G. , Seemala G. K. , Arcanjo M. O.
Published: August 2020

It has been noticed recently that the equatorial ionization anomaly (EIA) in the Brazilian eastern, middle, and western sectors present significant longitudinal variability within a short separation due to the presence of typical magnetic field structure over South America. Therefore, the main motivation of this study is to investigate day‐to‐day and month‐to‐month characteristics of the EIA in three closely spaced longitudinal sectors over the Brazilian region during the year 2016 in the descending phase of the solar activity. These three longitudinal sectors are perpendicular to the magnetic equator at its largest declination over the globe. The EIA showed a semiannual variation in all sectors with a major maximum during the summer, a minimum during the winter, and secondary maximum during spring. In addition, the EIA shows its classical behavior with a trough around the magnetic equator and crests at low latitudes (from ±15° to ±20°). When the EIA is not developed, the maximum ionization is located around the dip equatorial latitudes and the anomaly crest is absent. The number of days within 1 year that showed clear EIA development in the west, middle, and east sectors is 248 (78.2%), 236 (74.4%), and 265 (83.6%), respectively. The undeveloped/absence of EIA is also found often during the months of winter, and the numbers of such days during 2016 in the west, middle, and east are 69 (21.8%), 81 (25.6%), and 52 (16.4%), respectively. Also, the shape, strength, extent, and lifetimes of EIA crest have shown significant variabilities between the three sectors during different seasons. Further, a comparative analysis is carried out on the variations of EIA crest and lifetime between GPS observations and IRI‐2016 model, and the results are discussed.
Systematical Analyses of Global Ionospheric Disturbance Current Systems Caused by Multiple Processes: Penetration Electric Fields, Solar Wind Pressure Impulses, Magnetospheric Substorms, and ULF Waves
Authors: Huang Chao‐Song
Published: August 2020

We present the first systematic analysis of global ionospheric disturbance current systems caused by multiple processes of solar and magnetospheric origin, including reorientations of the interplanetary magnetic field (IMF), sudden changes in the solar wind dynamic pressure, magnetospheric sawtooth substorms, and ultralow frequency (ULF) waves. Measurements from global magnetometer networks are used to derive the equivalent disturbance currents from the polar cap to the equator. A surprising result is that the equivalent disturbance current systems are very similar, although the driving processes are completely different. The equivalent disturbance current system in response to IMF reorientation or substorm onset is characterized by a large vortex on the dayside and evening sector and a smaller vortex near dawn, and the polarity of the current vortices depends on the IMF direction. The equivalent disturbance current system caused by a sudden change in the solar wind pressure or by ULF waves consists of a single vortex at middle and low latitudes and a very small vortex above ~60° magnetic latitude near dawn. The similar disturbance current systems caused by different solar wind and magnetospheric processes suggest that the global distribution of the ionospheric currents is determined by the intrinsic property of the ionosphere. The global current system takes only ~1 min to completely reconstruct, indicating that the current system can reach a new steady state within 1 min. A scenario is proposed to explain the global distribution and fast reconstruction of the current systems.
NF-κB-dependent miR-31/155 biogenesis is essential for TNF-α-induced impairment of endothelial progenitor cell function
Authors: Kim Ji-Hee , Kim Ji-Yoon , Park Minsik , Kim Suji , Kim Taesam , Kim Joohwan , Choi Seunghwan , Park Wonjin , Hwang Jong Yun , Choe Jongseon , Ha Kwon-Soo , Won Moo-Ho , Ryoo Sungwoo , Kwon Young-Guen , Kim Young-Myeong
Published: August 2020

Endothelial progenitor cell (EPC) dysfunction impairs vascular function and remodeling in inflammation-associated diseases, including preeclampsia. However, the underlying mechanism of this inflammation-induced dysfunction remains unclear. In the present study, we found increases in TNF-α and miR-31/155 levels and reduced numbers of circulating EPCs in patients with preeclampsia. Patient-derived mononuclear cells (MNCs) cultured in autologous serum had decreased endothelial nitric oxide synthase (eNOS) expression, nitric oxide production, and differentiation into EPCs with angiogenic potential, and these effects were inhibited by a TNF-α-neutralizing antibody and miR-31/155 inhibitors. Moreover, TNF-α treatment of normal MNCs increased miR-31/155 biogenesis, decreased eNOS expression, reduced EPC differentiation, and impaired angiogenic potential. The TNF-α-induced impairment of EPC differentiation and function was rescued by NF-κB p65 knockdown or miR-31/155 inhibitors. In addition, treatment of MNCs with synthetic miR-31/155 or an eNOS inhibitor mimicked the inhibitory effects of TNF-α on eNOS expression and EPC functions. Moreover, transplantation of EPCs that had been differentiated from TNF-α-treated MNCs decreased neovascularization and blood perfusion in ischemic mouse hindlimbs compared with those of normally differentiated EPCs. These findings suggest that NF-κB activation is required for TNF-α-induced impairment of EPC mobilization, differentiation, and function via miR-31/155 biogenesis and eNOS downregulation. Our data provide a new role for NF-κB-dependent miR-31/155 in EPC dysfunction under the pathogenic conditions of inflammation-associated vascular diseases, including preeclampsia.
Mutant p53 induces Golgi tubulo-vesiculation driving a prometastatic secretome
Authors: Capaci Valeria , Bascetta Lorenzo , Fantuz Marco , Beznoussenko Galina V. , Sommaggio Roberta , Cancila Valeria , Bisso Andrea , Campaner Elena , Mironov Alexander A. , Wiśniewski Jacek R. , Ulloa Severino Luisa , Scaini Denis , Bossi Fleur , Lees Jodi , Alon Noa , Brunga Ledia , Malkin David , Piazza Silvano , Collavin Licio , Rosato Antonio , Bicciato Silvio , Tripodo Claudio , Mantovani Fiamma , Del Sal Giannino
Published: August 2020

TP53 missense mutations leading to the expression of mutant p53 oncoproteins are frequent driver events during tumorigenesis. p53 mutants promote tumor growth, metastasis and chemoresistance by affecting fundamental cellular pathways and functions. Here, we demonstrate that p53 mutants modify structure and function of the Golgi apparatus, culminating in the increased release of a pro-malignant secretome by tumor cells and primary fibroblasts from patients with Li-Fraumeni cancer predisposition syndrome. Mechanistically, interacting with the hypoxia responsive factor HIF1α, mutant p53 induces the expression of miR-30d, which in turn causes tubulo-vesiculation of the Golgi apparatus, leading to enhanced vesicular trafficking and secretion. The mut-p53/HIF1α/miR-30d axis potentiates the release of soluble factors and the deposition and remodeling of the ECM, affecting mechano-signaling and stromal cells activation within the tumor microenvironment, thereby enhancing tumor growth and metastatic colonization.
A blood miRNA signature associates with sporadic Creutzfeldt-Jakob disease diagnosis
Authors: Norsworthy Penny J. , Thompson Andrew G. B. , Mok Tze H. , Guntoro Fernando , Dabin Luke C. , Nihat Akin , Paterson Ross W. , Schott Jonathan M. , Collinge John , Mead Simon , Viré Emmanuelle A.
Published: August 2020

Sporadic Creutzfeldt-Jakob disease (sCJD) presents as a rapidly progressive dementia which is usually fatal within six months. No clinical blood tests are available for diagnosis or disease monitoring. Here, we profile blood microRNA (miRNA) expression in sCJD. Sequencing of 57 sCJD patients, and healthy controls reveals differential expression of hsa-let-7i-5p, hsa-miR-16-5p, hsa-miR-93-5p and hsa-miR-106b-3p. Downregulation of hsa-let-7i-5p, hsa-miR-16-5p and hsa-miR-93-5p replicates in an independent cohort using quantitative PCR, with concomitant upregulation of four mRNA targets. Absence of correlation in cross-sectional analysis with clinical phenotypes parallels the lack of association between rate of decline in miRNA expression, and rate of disease progression in a longitudinal cohort of samples from 21 patients. Finally, the miRNA signature shows a high level of accuracy in discriminating sCJD from Alzheimer’s disease. These findings highlight molecular alterations in the periphery in sCJD which provide information about differential diagnosis and improve mechanistic understanding of human prion diseases.
Molecular architecture and activation of the insecticidal protein Vip3Aa from Bacillus thuringiensis
Authors: Núñez-Ramírez Rafael , Huesa Juanjo , Bel Yolanda , Ferré Juan , Casino Patricia , Arias-Palomo Ernesto
Published: August 2020

Bacillus thuringiensis Vip3 (Vegetative Insecticidal Protein 3) toxins are widely used in biotech crops to control Lepidopteran pests. These proteins are produced as inactive protoxins that need to be activated by midgut proteases to trigger cell death. However, little is known about their three-dimensional organization and activation mechanism at the molecular level. Here, we have determined the structures of the protoxin and the protease-activated state of Vip3Aa at 2.9 Å using cryo-electron microscopy. The reconstructions show that the protoxin assembles into a pyramid-shaped tetramer with the C-terminal domains exposed to the solvent and the N-terminal region folded into a spring-loaded apex that, after protease activation, drastically remodels into an extended needle by a mechanism akin to that of influenza haemagglutinin. These results provide the molecular basis for Vip3 activation and function, and serves as a strong foundation for the development of more efficient insecticidal proteins.
Likely weakening of the Florida Current during the past century revealed by sea-level observations
Authors: Piecuch Christopher G.
Published: August 2020

The Florida Current marks the beginning of the Gulf Stream at Florida Straits, and plays an important role in climate. Nearly continuous measurements of Florida Current transport are available at 27°N since 1982. These data are too short for assessing possible multidecadal or centennial trends. Here I reconstruct Florida Current transport during 1909–2018 using probabilistic methods and principles of ocean physics applied to the available transport data and longer coastal sea-level records. Florida Current transport likely declined steadily during the past century. Transport since 1982 has likely been weaker on average than during 1909–1981. The weakest decadal-mean transport in the last 110 y likely took place in the past two decades. Results corroborate hypotheses that the deep branch of the overturning circulation declined over the recent past, and support relationships observed in climate models between the overturning and surface western boundary current transports at multidecadal and longer timescales.
ABL1-dependent OTULIN phosphorylation promotes genotoxic Wnt/β-catenin activation to enhance drug resistance in breast cancers
Authors: Wang Wei , Li Mingqi , Ponnusamy Suriyan , Chi Yayun , Xue Jingyan , Fahmy Beshoy , Fan Meiyun , Miranda-Carboni Gustavo A. , Narayanan Ramesh , Wu Jiong , Wu Zhao-Hui
Published: August 2020

Dysregulated Wnt/β-catenin activation plays a critical role in cancer progression, metastasis, and drug resistance. Genotoxic agents such as radiation and chemotherapeutics have been shown to activate the Wnt/β-catenin signaling although the underlying mechanism remains incompletely understood. Here, we show that genotoxic agent-activated Wnt/β-catenin signaling is independent of the FZD/LRP heterodimeric receptors and Wnt ligands. OTULIN, a linear linkage-specific deubiquitinase, is essential for the DNA damage-induced β-catenin activation. OTULIN inhibits linear ubiquitination of β-catenin, which attenuates its Lys48-linked ubiquitination and proteasomal degradation upon DNA damage. The association with β-catenin is enhanced by OTULIN Tyr56 phosphorylation, which depends on genotoxic stress-activated ABL1/c-Abl. Inhibiting OTULIN or Wnt/β-catenin sensitizes triple-negative breast cancer xenograft tumors to chemotherapeutics and reduces metastasis. Increased OTULIN levels are associated with aggressive molecular subtypes and poor survival in breast cancer patients. Thus, OTULIN-mediated Wnt/β-catenin activation upon genotoxic treatments promotes drug resistance and metastasis in breast cancers.
Adolescent frontal top-down neurons receive heightened local drive to establish adult attentional behavior in mice
Authors: Nabel Elisa M. , Garkun Yury , Koike Hiroyuki , Sadahiro Masato , Liang Ana , Norman Kevin J. , Taccheri Giulia , Demars Michael P. , Im Susanna , Caro Keaven , Lopez Sarah , Bateh Julia , Hof Patrick R. , Clem Roger L. , Morishita Hirofumi
Published: August 2020

Frontal top-down cortical neurons projecting to sensory cortical regions are well-positioned to integrate long-range inputs with local circuitry in frontal cortex to implement top-down attentional control of sensory regions. How adolescence contributes to the maturation of top-down neurons and associated local/long-range input balance, and the establishment of attentional control is poorly understood. Here we combine projection-specific electrophysiological and rabies-mediated input mapping in mice to uncover adolescence as a developmental stage when frontal top-down neurons projecting from the anterior cingulate to visual cortex are highly functionally integrated into local excitatory circuitry and have heightened activity compared to adulthood. Chemogenetic suppression of top-down neuron activity selectively during adolescence, but not later periods, produces long-lasting visual attentional behavior deficits, and results in excessive loss of local excitatory inputs in adulthood. Our study reveals an adolescent sensitive period when top-down neurons integrate local circuits with long-range connectivity to produce attentional behavior.
Elevated rates of autism, other neurodevelopmental and psychiatric diagnoses, and autistic traits in transgender and gender-diverse individuals
Authors: Warrier Varun , Greenberg David M. , Weir Elizabeth , Buckingham Clara , Smith Paula , Lai Meng-Chuan , Allison Carrie , Baron-Cohen Simon
Published: August 2020

It is unclear whether transgender and gender-diverse individuals have elevated rates of autism diagnosis or traits related to autism compared to cisgender individuals in large non-clinic-based cohorts. To investigate this, we use five independently recruited cross-sectional datasets consisting of 641,860 individuals who completed information on gender, neurodevelopmental and psychiatric diagnoses including autism, and measures of traits related to autism (self-report measures of autistic traits, empathy, systemizing, and sensory sensitivity). Compared to cisgender individuals, transgender and gender-diverse individuals have, on average, higher rates of autism, other neurodevelopmental and psychiatric diagnoses. For both autistic and non-autistic individuals, transgender and gender-diverse individuals score, on average, higher on self-report measures of autistic traits, systemizing, and sensory sensitivity, and, on average, lower on self-report measures of empathy. The results may have clinical implications for improving access to mental health care and tailoring adequate support for transgender and gender-diverse individuals.
Epsin-mediated degradation of IP3R1 fuels atherosclerosis
Authors: Dong Yunzhou , Lee Yang , Cui Kui , He Ming , Wang Beibei , Bhattacharjee Sudarshan , Zhu Bo , Yago Tadayuki , Zhang Kun , Deng Lin , Ouyang Kunfu , Wen Aiyun , Cowan Douglas B. , Song Kai , Yu Lili , Brophy Megan L. , Liu Xiaolei , Wylie-Sears Jill , Wu Hao , Wong Scott , Cui Guanglin , Kawashima Yusuke , Matsumoto Hiroyuki , Kodera Yoshio , Wojcikiewicz Richard J. H. , Srivastava Sanjay , Bischoff Joyce , Wang Da-Zhi , Ley Klaus , Chen Hong
Published: August 2020

The epsin family of endocytic adapter proteins are widely expressed, and interact with both proteins and lipids to regulate a variety of cell functions. However, the role of epsins in atherosclerosis is poorly understood. Here, we show that deletion of endothelial epsin proteins reduces inflammation and attenuates atherosclerosis using both cell culture and mouse models of this disease. In atherogenic cholesterol-treated murine aortic endothelial cells, epsins interact with the ubiquitinated endoplasmic reticulum protein inositol 1,4,5-trisphosphate receptor type 1 (IP3R1), which triggers proteasomal degradation of this calcium release channel. Epsins potentiate its degradation via this interaction. Genetic reduction of endothelial IP3R1 accelerates atherosclerosis, whereas deletion of endothelial epsins stabilizes IP3R1 and mitigates inflammation. Reduction of IP3R1 in epsin-deficient mice restores atherosclerotic progression. Taken together, epsin-mediated degradation of IP3R1 represents a previously undiscovered biological role for epsin proteins and may provide new therapeutic targets for the treatment of atherosclerosis and other diseases.
Delocalization of exciton and electron wavefunction in non-fullerene acceptor molecules enables efficient organic solar cells
Authors: Zhang Guichuan , Chen Xian-Kai , Xiao Jingyang , Chow Philip C. Y. , Ren Minrun , Kupgan Grit , Jiao Xuechen , Chan Christopher C. S. , Du Xiaoyan , Xia Ruoxi , Chen Ziming , Yuan Jun , Zhang Yunqiang , Zhang Shoufeng , Liu Yidan , Zou Yingping , Yan He , Wong Kam Sing , Coropceanu Veaceslav , Li Ning , Brabec Christoph J. , Bredas Jean-Luc , Yip Hin-Lap , Cao Yong
Published: August 2020

A major challenge for organic solar cell (OSC) research is how to minimize the tradeoff between voltage loss and charge generation. In early 2019, we reported a non-fullerene acceptor (named Y6) that can simultaneously achieve high external quantum efficiency and low voltage loss for OSC. Here, we use a combination of experimental and theoretical modeling to reveal the structure-property-performance relationships of this state-of-the-art OSC system. We find that the distinctive π–π molecular packing of Y6 not only exists in molecular single crystals but also in thin films. Importantly, such molecular packing leads to (i) the formation of delocalized and emissive excitons that enable small non-radiative voltage loss, and (ii) delocalization of electron wavefunctions at donor/acceptor interfaces that significantly reduces the Coulomb attraction between interfacial electron-hole pairs. These properties are critical in enabling highly efficient charge generation in OSC systems with negligible donor-acceptor energy offset.