bluuebunny/crossref_metadata_2025 huggingface dataset:
Dual Sounding Rocket and C/NOFS Satellite Observations of DC Electric Fields and Plasma Density in the Equatorial E‐ and F‐Region Ionosphere at Sunset
Authors: Pfaff R. , Kudeki E. , Freudenreich H. , Rowland D. , Larsen M. , Klenzing J.
Published: April 2022

E × B plasma drifts and plasma number density were measured on two NASA rockets launched simultaneously at sunset from Kwajalein Atoll with apogees of 182 and 331 km, with similar, coincident measurements gathered on the Communications/Navigation Outage Forecasting System (C/NOFS) satellite at 390 km. The combined measurements portray a highly dynamic ionosphere in a narrow range of local time and altitude, providing evidence of vortex‐like motions. Although the vertical plasma drift was upwards, its magnitude was not constant, increasing between ∼150 and 250 km altitude where the plasma density was reduced. The zonal plasma drifts displayed a shear with altitude, changing from eastward to westward flow below 270 km, coincident with the larger upward drifts and consistent with the maintenance of the vortex flow. The plasma density on the western flank was highly structured compared to the eastern flank, despite the fact that the western region corresponded to slightly earlier local times. These observations illustrate that the low latitude ionosphere at sunset must be considered as an ensemble of interconnected flows encompassing an evolving “theater,” as opposed to a background that simply unfolds linearly with respect to local time. The observations also underscore how satellites at high altitudes do not capture the highly dynamic ionosphere and thermosphere at the lower altitudes which are critical for understanding the electrodynamics system. Such motions set the stage for large scale plasma instabilities to form later in the evening, as observed by radars at Kwajalein and subsequent passes of the C/NOFS satellite.
A Comparative Study on the Factors Controlling the Cusp Auroral Intensity Between the Northern and Southern Hemispheres
Authors: Qiu Hui‐Xuan , Han De‐Sheng , Zhang Hong‐Da , Yang Hui‐Gen , Feng Hui‐Ting , Yu Xi , Shi Run , Zhou Su , Zhang Y.‐L.
Published: April 2022

The previous study has indicated that the interplanetary magnetic field (IMF) By and solar wind flow speed (Vsw) have crucial effects on the cusp auroral intensity in the Northern Hemisphere. However, it is not clear how these factors influence the cusp aurora in the Southern Hemisphere. Using DMSP/SUSSI observations from 2004 to 2017 during non‐storm periods, we compared the factors affecting the intensity of cusp aurora between the Northern and Southern Hemispheres by dividing the observations into weak‐ and intense‐emission events. We found that the auroral intensity in the southern cusp: (a) has a positive correlation with solar wind power input, (b) is statistically weak under southward IMF conditions, and (c) is critically controlled by the IMF By and Vsw. These results are essentially consistent with those obtained in the Northern Hemisphere. However, the IMF By effect shows apparent interhemispheric asymmetry, that is, the IMF By effect reaches the maximum at 2 nT in the Northern Hemisphere, but at −2 nT in the Southern Hemisphere. Further analysis shows that the 2‐nT deviations disappear after dividing all events by season and the IMF By distributions of intense‐emission events show clear seasonal difference. Based on these results, we suggest that the dependence of the cusp auroral intensity on the IMF By is not only controlled by −Vsw × By field, but also affected by season.
Influence of the Quasi‐Biennial Oscillation on the Spatial Structure of the Wintertime Arctic Oscillation
Authors: Cai Qingyu , Chen Wen , Chen Shangfeng , Ma Tianjiao , Garfinkel Chaim I.
Published: April 2022

This study reveals that the Quasi‐Biennial Oscillation (QBO) has a marked impact on the spatial structure of the Arctic Oscillation (AO) in boreal winter. In particular, the North Pacific center (NPC) of the AO is stronger during the westerly phase of the QBO (WQBO) than the easterly phase of the QBO (EQBO). In other words, the variability associated with the AO over the North Pacific is stronger in WQBO years than EQBO years, even though the overall variability is insensitive to QBO phase. The QBO is suggested to influence the spatial pattern of the winter AO mainly via modulating the intensity of the stratospheric polar vortex, with a stronger stratospheric polar vortex during WQBO than EQBO years. A stronger stratospheric polar vortex can lead to more planetary wave refraction and facilitate the eastward propagation of wave activity flux from the mid‐latitude North Pacific to the North Atlantic. Thus an enhanced connection between North Pacific and North Atlantic atmospheric variability is established, and a more prominent NPC of the AO occurs in WQBO years. In addition, the modulation of the AO structure by the QBO and the associated physical process is supported by output from the CNRM‐CM6‐1 model. Our results indicate that, for seasonal climate prediction in North America based on the AO, WQBO leads to a larger predictable signal while EQBO leads to reduced skill.
Effective Radiative Forcings Due To Anthropogenic Emission Changes Under Covid‐19 and Post‐Pandemic Recovery Scenarios
Authors: Yu Xiaochao , Zhang Hua , Xie Bing , Wang Zhili , Zhao Shuyun , Zhao Defeng
Published: April 2022

With the continuation of the Coronavirus Disease 2019 (Covid‐19) pandemic, the impacts of this catastrophe on anthropogenic emissions are no longer limited to its early stage. This study quantitatively estimates effective radiative forcings (ERFs) due to anthropogenic well‐mixed greenhouse gases (WMGHGs) and aerosols for the period 2020–2050 under the three latest Covid‐19 economic‐recovery scenarios using an aerosol‐climate model. The results indicate that reductions in both WMGHG and aerosol emissions under the Covid‐19 green recoveries lead to increases ranging from 0 to 0.3 W m−2 in global annual mean anthropogenic ERF over the period 2020–2050 relative to the Shared Socioeconomic Pathway 2‐4.5 scenario (the baseline case). These positive ERFs are mainly attributed to the rapid and dramatic decreases in atmospheric aerosol content that increase net shortwave radiative flux at the top of atmosphere via weakening the direct aerosol effect and low cloud cover. At the regional scale, reductions in aerosols contribute to positive ERFs throughout the Northern Hemisphere, while the decreased WMGHGs dominate negative ERFs over the areas away from aerosol pollution, such as the Southern Hemisphere oceans. This drives a strong interhemispheric contrast of ERFs. In contrast, the increased anthropogenic emissions under the fossil‐fueled recovery scenario lead to an increase of 0.3 W m−2 in global annual mean ERF in 2050 compared with the baseline case, primarily due to the contribution of WMGHG ERFs. The regional ERF changes are highly dependent on local cloud radiative effects.
Observed Mixing at the Flanks of Maud Rise in the Weddell Sea
Authors: Mohrmann M. , Swart S. , Heuzé C.
Published: April 2022

Maud Rise is a seamount in the eastern Weddell Sea and the location of polynyas and a persistent halo of reduced sea ice. We present novel in situ data from two profiling floats with up to daily resolved hydrographic profiles in this region. The water properties below the mixed layer of the Maud Rise region are significantly correlated with bathymetric depth; thus, the Maud Rise flank defines the front between the Warm Deep Water of the abyssal ocean and the colder Taylor cap over Maud Rise. We analyze the spiciness curvature in density space to quantify the observed frequency or magnitude of intrusions, which are substantially increased along the flanks of Maud Rise. These intrusions are indicative of enhanced lateral and vertical mixing along heavily sloping isopycnals, creating favorable conditions for thermobaric and double diffusive convection and likely facilitating the formation of the Maud Rise halo and polynyas.
Machine Learning Gravity Wave Parameterization Generalizes to Capture the QBO and Response to Increased CO2
Authors: Espinosa Zachary I. , Sheshadri Aditi , Cain Gerald R. , Gerber Edwin P. , DallaSanta Kevin J.
Published: April 2022

We present single‐column gravity wave parameterizations (GWPs) that use machine learning to emulate non‐orographic gravity wave (GW) drag and demonstrate their ability to generalize out‐of‐sample. A set of artificial neural networks (ANNs) are trained to emulate the momentum forcing from a conventional GWP in an idealized climate model, given only one view of the annual cycle and one phase of the Quasi‐Biennial Oscillation (QBO). We investigate the sensitivity of offline and online performance to the choice of input variables and complexity of the ANN. When coupled with the model, moderately complex ANNs accurately generate full cycles of the QBO. When the model is forced with enhanced CO2, its climate response with the ANN matches that generated with the physics‐based GWP. That ANNs can accurately emulate an existing scheme and generalize to new regimes given limited data suggests the potential for developing GWPs from observational estimates of GW momentum transport.
Localizing the Southern Ocean Biogeochemical Divide
Authors: Xie Yinghuan , Tamsitt Veronica , Bach Lennart T.
Published: April 2022

The meridional overturning circulation consists of an upper and lower cell. The Southern Ocean Biogeochemical Divide (SOBD) is the boundary between the two cells in the surface of the Southern Ocean, but its location is poorly constrained. Localizing the SOBD is important because biological nutrient utilization north and south of the SOBD have fundamentally different consequences for global ocean primary production and carbon sequestration. Here, we aim to localize the SOBD by releasing virtual Lagrangian particles south of 40°S in an eddying ocean sea‐ice model and compare simulation results with observations. We find that the SOBD is a circumpolar band, where different sectors are shaped by different oceanographic features: (a) Ekman transport, (b) the γ = 27.6 kg m−3 neutral density outcrop, and (c) fronts associated with the Antarctic Circumpolar Current. Our findings help to understand how nutrient utilization in different parts of the Southern Ocean affects the biologically driven carbon sequestration.
A flexible and wearable NO2 gas detection and early warning device based on a spraying process and an interdigital electrode at room temperature
Authors: Zhang Fuzheng , Lin Qijing , Han Feng , Wang Zuowei , Tian Bian , Zhao Libo , Dong Tao , Jiang Zhuangde
Published: April 2022

Flexible sensors used to detect NO2 gas generally have problems such as poor repeatability, high operating temperature, poor selectivity, and small detection range. In this work, a new spraying platform with a simple structure, low cost, and good film-forming consistency was designed and built to make a sensitive film (rGO/SnO2) for NO2 gas sensors. The relationship between the solid content of rGO and SnO2 nanoparticles, annealing temperature, and sensor performance was studied. The results show that the interdigital electrode-sensitive film formed by spraying 0.25 ml of a 0.4 wt% rGO/SnO2 mixture and annealing at 250 °C exhibited the best comprehensive performance for NO2 detection. The sensor’s response value for 100 ppm NO2 gas was 0.2640 at room temperature (25 °C), and the response time and recovery time were 412.4 s and 587.3 s, respectively. In the range of 20–100 ppm, the relationship between the response and NO2 concentration was linear, and the correlation coefficient was 0.9851. In addition, a soft-monitoring node module with an overlimit warning function for NO2 gas was designed and manufactured based on flexible electronics. Finally, the flexible sensor and node module were embedded into woven fabric that could be used to make a mask or a watch that could detect NO2 gas, realizing the practical application of flexible NO2 gas sensors in the field of wearable electronics.
Introducing the brain erythropoietin circle to explain adaptive brain hardware upgrade and improved performance
Authors: Ehrenreich Hannelore , Garcia-Agudo Laura Fernandez , Steixner-Kumar Agnes A. , Wilke Justus B. H. , Butt Umer Javed
Published: April 2022

Preface

Executive functions, learning, attention, and processing speed are imperative facets of cognitive performance, affected in neuropsychiatric disorders. In clinical studies on different patient groups, recombinant human (rh) erythropoietin (EPO) lastingly improved higher cognition and reduced brain matter loss. Correspondingly, rhEPO treatment of young rodents or EPO receptor (EPOR) overexpression in pyramidal neurons caused remarkable and enduring cognitive improvement, together with enhanced hippocampal long-term potentiation. The ‘brain hardware upgrade’, underlying these observations, includes an EPO induced ~20% increase in pyramidal neurons and oligodendrocytes in cornu ammonis hippocampi in the absence of elevated DNA synthesis. In parallel, EPO reduces microglia numbers and dampens their activity and metabolism as prerequisites for undisturbed EPO-driven differentiation of pre-existing local neuronal precursors. These processes depend on neuronal and microglial EPOR. This novel mechanism of powerful postnatal neurogenesis, outside the classical neurogenic niches, and on-demand delivery of new cells, paralleled by dendritic spine increase, let us hypothesize a physiological procognitive role of hypoxia-induced endogenous EPO in brain, which we imitate by rhEPO treatment. Here we delineate the brain EPO circle as working model explaining adaptive ‘brain hardware upgrade’ and improved performance. In this fundamental regulatory circle, neuronal networks, challenged by motor-cognitive tasks, drift into transient ‘functional hypoxia’, thereby triggering neuronal EPO/EPOR expression.
Myeloablative conditioning with thiotepa-busulfan-fludarabine does not improve the outcome of patients transplanted with active leukemia: final results of the GITMO prospective trial GANDALF-01
Authors: Bonifazi Francesca , Pavoni Chiara , Peccatori Jacopo , Giglio Fabio , Arpinati Mario , Busca Alessandro , Bernasconi Paolo , Grassi Anna , Iori Anna Paola , Patriarca Francesca , Brunello Lucia , Di Grazia Carmen , Carella Angelo Michele , Cilloni Daniela , Picardi Alessandra , Proia Anna , Santarone Stella , Sorasio Roberto , Carluccio Paola , Chiusolo Patrizia , Cupri Alessandra , Luppi Mario , Nozzoli Chiara , Baronciani Donatella , Casini Marco , Grillo Giovanni , Musso Maurizio , Onida Francesco , Palazzo Giulia , Parma Matteo , Tringali Stefania , Vacca Adriana , Vallisa Daniele , Sacchi Nicoletta , Oldani Elena , Masciulli Arianna , Gheorghiu Angela , Girmenia Corrado , Martino Massimo , Bruno Benedetto , Rambaldi Alessandro , Ciceri Fabio ,   on behalf of GITMO
Published: April 2022

The outcome of refractory/relapsed (R/R) acute leukemias is still dismal and their treatment represents an unmet clinical need. However, allogeneic transplantation (allo-HSCT) remains the only potentially curative approach in this setting. A prospective study (GANDALF-01, NCT01814488; EUDRACT:2012-004008-37) on transplantation with alternative donors had been run by GITMO using a homogeneous myeloablative conditioning regimen with busulfan, thiotepa and fludarabine while GVHD prophylaxis was stratified by donor type. The study enrolled 101 patients; 90 found an alternative donor and 87 ultimately underwent allo-HSCT. Two-year overall survival of the entire and of the transplant population (primary endpoint) were 19% and 22%, without significant differences according to disease, donor type and disease history (relapsed vs refractory patients). Two-year progression-free survival was 19% and 17% respectively. The cumulative incidences of relapse and non-relapse mortality were 49% and 33% at two years. Acute grade II-IV and chronic GVHD occurred in 23 and 10 patients. Dose intensification with a myeloablative two-alkylating regimen as sole strategy for transplanting R/R acute leukemia does seem neither to improve the outcome nor to control disease relapse. A pre-planned relapse prevention should be included in the transplant strategy in this patient population.
Targeted P2X7/NLRP3 signaling pathway against inflammation, apoptosis, and pyroptosis of retinal endothelial cells in diabetic retinopathy
Authors: Kong Hui , Zhao Hongran , Chen Tianran , Song Yanling , Cui Yan
Published: April 2022

Retinal endothelial cells (RECs) are the primary target cells for diabetes-induced vascular damage. The P2X7/NLRP3 pathway plays an essential role in amplifying inflammation via an ATP feedback loop, promoting the inflammatory response, pyroptosis, and apoptosis of RECs in the early stages of diabetic retinopathy induced by hyperglycemia and inflammation. 3TC, a type of nucleoside reverse transcriptase inhibitor, is effective against inflammation, as it can targeting formation of the P2X7 large pore formation. Hence, our aim was to evaluated the anti-inflammatory effects and potential mechanisms of action of 3TC in vitro in retinal microvascular endothelial cells treated with high-glucose (HG) and lipopolysaccharide (LPS), as well as in vivo in the retinas of C57BL/6J male mice with streptozotocin-induced diabetes. The expression of inflammasome-related proteins P2X7 and NLRP3, and apoptosis in the retinas of 3TC-treated diabetic mice were compared to those of untreated diabetic mice. Furthermore, the anti-inflammatory, anti-apoptotic, and anti-pyroptotic effects of 3TC were evaluated in vitro in cultured mice retinal endothelial cells. Co-application of HG and LPS significantly increased the secretion of IL-6, IL-1β, and TNF-α, and ATP levels, whereas 3TC decreased cell inflammation, apoptosis, and pyroptosis. Inhibition of P2X7R and NLRP3 inflammasome activation decreased NLRP3 inflammasome-mediated injury. 3TC prevented cytokine and ATP release following co-application of HG and LPS/BzATP. Our findings provide new insights regarding the mechanisms of action of 3TC in diabetic environment-induced retinal injury, including apoptosis and pyroptosis.
Attribution of 2020 hurricane season extreme rainfall to human-induced climate change
Authors: Reed Kevin A. , Wehner Michael F. , Zarzycki Colin M.
Published: April 2022

The 2020 North Atlantic hurricane season was one of the most active on record, causing heavy rains, strong storm surges, and high winds. Human activities continue to increase the amount of greenhouse gases in the atmosphere, resulting in an increase of more than 1 °C in the global average surface temperature in 2020 compared to 1850. This increase in temperature led to increases in sea surface temperature in the North Atlantic basin of 0.4–0.9 °C during the 2020 hurricane season. Here we show that human-induced climate change increased the extreme 3-hourly storm rainfall rates and extreme 3-day accumulated rainfall amounts during the full 2020 hurricane season for observed storms that are at least tropical storm strength (>18 m/s) by 10 and 5%, respectively. When focusing on hurricane strength storms (>33 m/s), extreme 3-hourly rainfall rates and extreme 3-day accumulated rainfall amounts increase by 11 and 8%, respectively.
Population-scale long-read sequencing uncovers transposable elements associated with gene expression variation and adaptive signatures in Drosophila
Authors: Rech Gabriel E. , Radío Santiago , Guirao-Rico Sara , Aguilera Laura , Horvath Vivien , Green Llewellyn , Lindstadt Hannah , Jamilloux Véronique , Quesneville Hadi , González Josefa
Published: April 2022

High quality reference genomes are crucial to understanding genome function, structure and evolution. The availability of reference genomes has allowed us to start inferring the role of genetic variation in biology, disease, and biodiversity conservation. However, analyses across organisms demonstrate that a single reference genome is not enough to capture the global genetic diversity present in populations. In this work, we generate 32 high-quality reference genomes for the well-known model species D. melanogaster and focus on the identification and analysis of transposable element variation as they are the most common type of structural variant. We show that integrating the genetic variation across natural populations from five climatic regions increases the number of detected insertions by 58%. Moreover, 26% to 57% of the insertions identified using long-reads were missed by short-reads methods. We also identify hundreds of transposable elements associated with gene expression variation and new TE variants likely to contribute to adaptive evolution in this species. Our results highlight the importance of incorporating the genetic variation present in natural populations to genomic studies, which is essential if we are to understand how genomes function and evolve.
Distinct molecular and immune hallmarks of inflammatory arthritis induced by immune checkpoint inhibitors for cancer therapy
Authors: Kim Sang T. , Chu Yanshuo , Misoi Mercy , Suarez-Almazor Maria E. , Tayar Jean H. , Lu Huifang , Buni Maryam , Kramer Jordan , Rodriguez Emma , Hussain Zulekha , Neelapu Sattva S. , Wang Jennifer , Shah Amishi Y. , Tannir Nizar M. , Campbell Matthew T. , Gibbons Don L. , Cascone Tina , Lu Charles , Blumenschein George R. , Altan Mehmet , Lim Bora , Valero Vincente , Loghin Monica E. , Tu Janet , Westin Shannon N. , Naing Aung , Garcia-Manero Guillermo , Abdel-Wahab Noha , Tawbi Hussein A. , Hwu Patrick , Oliva Isabella C. Glitza , Davies Michael A. , Patel Sapna P. , Zou Jun , Futreal Andrew , Diab Adi , Wang Linghua , Nurieva Roza
Published: April 2022

Immune checkpoint inhibitors are associated with immune-related adverse events (irAEs), including arthritis (arthritis-irAE). Management of arthritis-irAE is challenging because immunomodulatory therapy for arthritis should not impede antitumor immunity. Understanding of the mechanisms of arthritis-irAE is critical to overcome this challenge, but the pathophysiology remains unknown. Here, we comprehensively analyze peripheral blood and/or synovial fluid samples from 20 patients with arthritis-irAE, and unmask a prominent Th1-CD8+ T cell axis in both blood and inflamed joints. CX3CR1hi CD8+ T cells in blood and CXCR3hi CD8+ T cells in synovial fluid, the most clonally expanded T cells, significantly share TCR repertoires. The migration of blood CX3CR1hi CD8+ T cells into joints is possibly mediated by CXCL9/10/11/16 expressed by myeloid cells. Furthermore, arthritis after combined CTLA-4 and PD-1 inhibitor therapy preferentially has enhanced Th17 and transient Th1/Th17 cell signatures. Our data provide insights into the mechanisms, predictive biomarkers, and therapeutic targets for arthritis-irAE.
Pace of passive margin tectonism revealed by U-Pb dating of fracture-filling calcite
Authors: Amidon William H. , Kylander-Clark Andrew R. C. , Barr Matthew N. , Graf Samuel F. I. , West David P.
Published: April 2022

A growing body of evidence demonstrates that Atlantic-style passive margins have experienced episodes of uplift and volcanism in response to changes in mantle circulation long after cessation of rifting. Passive margins are thus an attractive archive from which to retrieve records of mantle circulation and lithospheric alteration. However, this archive remains under-utilized due to difficulty in deciphering the surficial records of passive margin tectonism and linking them to seismic velocity structure. Here we present a new approach to unraveling the tectonic history of passive margins using U-Pb dating of calcite in faults and fractures along the eastern North American margin. These ages show a 40 Myr long period of continuous fracturing and faulting from ~115 to 75 Ma followed by another episode in Mio-Pliocene time. We argue that the former event represents a response to Cretaceous lithospheric alteration whereas the latter records development of modern relief in the northern Appalachians.
In situ dual doping for constructing efficient CO2-to-methanol electrocatalysts
Authors: Li Pengsong , Bi Jiahui , Liu Jiyuan , Zhu Qinggong , Chen Chunjun , Sun Xiaofu , Zhang Jianling , Han Buxing
Published: April 2022

Methanol is a highly desirable product of CO2 electroreduction due to its wide array of industrial applications. However, the development of CO2-to-methanol electrocatalysts with high performance is still challenging. Here we report an operationally simple in situ dual doping strategy to construct efficient CO2-to-methanol electrocatalysts. In particular, when using Ag,S-Cu2O/Cu as electrocatalyst, the methanol Faradaic efficiency (FE) could reach 67.4% with a current density as high as 122.7 mA cm−2 in an H-type cell using 1-butyl-3-methylimidazolium tetrafluoroborate/H2O as the electrolyte, while the current density was below 50 mA cm−2 when the FE was greater than 50% over the reported catalysts. Experimental and theoretical studies suggest that the anion S can effectively adjust the electronic structure and morphology of the catalysts in favor of the methanol pathway, whereas the cation Ag suppresses the hydrogen evolution reaction. Their synergistic interactions with host material enhance the selectivity and current density for methanol formation. This work opens a way for designing efficient catalysts for CO2 electroreduction to methanol.
Multi-animal pose estimation, identification and tracking with DeepLabCut
Authors: Lauer Jessy , Zhou Mu , Ye Shaokai , Menegas William , Schneider Steffen , Nath Tanmay , Rahman Mohammed Mostafizur , Di Santo Valentina , Soberanes Daniel , Feng Guoping , Murthy Venkatesh N. , Lauder George , Dulac Catherine , Mathis Mackenzie Weygandt , Mathis Alexander
Published: April 2022

Estimating the pose of multiple animals is a challenging computer vision problem: frequent interactions cause occlusions and complicate the association of detected keypoints to the correct individuals, as well as having highly similar looking animals that interact more closely than in typical multi-human scenarios. To take up this challenge, we build on DeepLabCut, an open-source pose estimation toolbox, and provide high-performance animal assembly and tracking—features required for multi-animal scenarios. Furthermore, we integrate the ability to predict an animal’s identity to assist tracking (in case of occlusions). We illustrate the power of this framework with four datasets varying in complexity, which we release to serve as a benchmark for future algorithm development.
Urban growth modelling and social vulnerability assessment for a hazardous Kathmandu Valley
Authors: Mesta Carlos , Cremen Gemma , Galasso Carmine
Published: April 2022

In our rapidly urbanizing world, many hazard-prone regions face significant challenges regarding risk-informed urban development. This study addresses this issue by investigating evolving spatial interactions between natural hazards, ever-increasing urban areas, and social vulnerability in Kathmandu Valley, Nepal. The methodology considers: (1) the characterization of flood hazard and liquefaction susceptibility using pre-existing global models; (2) the simulation of future urban built-up areas using the cellular-automata SLEUTH model; and (3) the assessment of social vulnerability, using a composite index tailored for the case-study area. Results show that built-up areas in Kathmandu Valley will increase to 352 km2by 2050, effectively doubling the equivalent 2018 figure. The most socially vulnerable villages will account for 29% of built-up areas in 2050, 11% more than current levels. Built-up areas in the 100-year and 1000-year return period floodplains will respectively increase from 38 km2and 49 km2today to 83 km2and 108 km2in 2050. Additionally, built-up areas in liquefaction-susceptible zones will expand by 13 km2to 47 km2. This study illustrates how, where, and to which extent risks from natural hazards can evolve in socially vulnerable regions. Ultimately, it emphasizes an urgent need to implement effective policy measures for reducing tomorrow's natural-hazard risks.
Experimental evolution of active Brownian grains driven by quantum effects in superfluid helium
Authors: Petrov Oleg F. , Boltnev Roman E. , Vasiliev Mikhail M.
Published: April 2022

Complex structures, consisting of a large number of interacting subsystems, have the ability to self-organize and evolve, when the scattering of energy coming from the outside ensures the maintenance of stationary ordered structures with an entropy less than the equilibrium entropy. One of the fundamental problems here is the role of quantum phenomena in the evolution of macroscopic objects. We provide experimental evidence for the active Brownian motion and evolution of structures driven by quantum effects for micron-sized grains levitating in superfluid helium. The active Brownian motion of grains was induced by quantum turbulence during the absorption of laser irradiation by grains. The intensity of Brownian motion associated with quantum vortices increased by 6–7 orders of magnitude compared to the values from the Einstein formula. We observed the grain structures in a state far from thermodynamic equilibrium and their evolution to more complex organized structures with lower entropy due to the quantum mechanism of exceedingly high entropy loss in superfluid helium.
Systemic bis-phosphinic acid derivative restores chloride transport in Cystic Fibrosis mice
Authors: da Cunha Mélanie Faria , Pranke Iwona , Sassi Ali , Schreiweis Christiane , Moriceau Stéphanie , Vidovic Dragana , Hatton Aurélie , Carlon Mariane Sylvia , Creste Geordie , Berhal Farouk , Prestat Guillaume , Freund Romain , Odolczyk Norbert , Jais Jean Philippe , Gravier-Pelletier Christine , Zielenkiewicz Piotr , Jullien Vincent , Hinzpeter Alexandre , Oury Franck , Edelman Aleksander , Sermet-Gaudelus Isabelle
Published: April 2022

Mutations in the Cystic Fibrosis Transmembrane Conductance Regulator gene (CFTR) are responsible for Cystic Fibrosis (CF). The most common CF-causing mutation is the deletion of the 508th amino-acid of CFTR (F508del), leading to dysregulation of the epithelial fluid transport in the airway’s epithelium and the production of a thickened mucus favoring chronic bacterial colonization, sustained inflammation and ultimately respiratory failure. c407 is a bis-phosphinic acid derivative which corrects CFTR dysfunction in epithelial cells carrying the F508del mutation. This study aimed to investigate c407 in vivo activity in the F508del Cftrtm1Eur murine model of CF. Using nasal potential difference measurement, we showed that in vivo administration of c407 by topical, short-term intraperitoneal and long-term subcutaneous route significantly increased the CFTR dependent chloride (Cl−) conductance in F508del Cftrtm1Eur mice. This functional improvement was correlated with a relocalization of F508del-cftr to the apical membrane in nasal epithelial cells. Importantly, c407 long-term administration was well tolerated and in vitro ADME toxicologic studies did not evidence any obvious issue. Our data provide the first in vivo preclinical evidence of c407 efficacy and absence of toxicity after systemic administration for the treatment of Cystic Fibrosis.
Stress pulmonary circulation parameters assessed by a cardiovascular magnetic resonance in patients after a heart transplant
Authors: Opatřil Lukáš , Panovsky Roman , Mojica-Pisciotti Mary , Máchal Jan , Krejčí Jan , Holeček Tomáš , Masárová Lucia , Feitová Věra , Godava Július , Kincl Vladimír , Kepák Tomáš , Závodná Gabriela , Špinarová Lenka
Published: April 2022

Rest pulmonary circulation parameters such as pulmonary transit time (PTT), heart rate corrected PTT (PTTc) and pulmonary transit beats (PTB) can be evaluated using several methods, including the first-pass perfusion from cardiovascular magnetic resonance. As previously published, up to 58% of patients after HTx have diastolic dysfunction detectable only in stress conditions. By using adenosine stress perfusion images, stress analogues of the mentioned parameters can be assessed. By dividing stress to rest biomarkers, potential new ratio parameters (PTT ratio and PTTc ratio) can be obtained. The objectives were to (1) provide more evidence about stress pulmonary circulation biomarkers, (2) present stress to rest ratio parameters, and (3) assess these biomarkers in patients with presumed diastolic dysfunction after heart transplant (HTx) and in childhood cancer survivors (CCS) without any signs of diastolic dysfunction. In this retrospective study, 48 patients after HTx, divided into subgroups based on echocardiographic signs of diastolic dysfunction (41 without, 7 with) and 39 CCS were enrolled. PTT was defined as the difference between the onset time of the signal intensity increase in the left and the right ventricle. PTT in rest conditions were without significant differences when comparing the CCS and HTx subgroup without diastolic dysfunction (4.96 ± 0.93 s vs. 5.51 ± 1.14 s, p = 0.063) or with diastolic dysfunction (4.96 ± 0.93 s vs. 6.04 ± 1.13 s, p = 0.13). However, in stress conditions, both PTT and PTTc were significantly lower in the CCS group than in the HTx subgroups, (PTT: 3.76 ± 0.78 s vs. 4.82 ± 1.03 s, p < 0.001; 5.52 ± 1.56 s, p = 0.002). PTT ratio and PTTc ratio were below 1 in all groups. In conclusion, stress pulmonary circulation parameters obtained from CMR showed prolonged PTT and PTTc in HTx groups compared to CCS, which corresponds with the presumption of underlying diastolic dysfunction. The ratio parameters were less than 1.
Laminin matrix regulates beta-cell FGFR5 expression to enhance glucose-stimulated metabolism
Authors: Pal Vidhant , Wang Yufeng , Regeenes Romario , Kilkenny Dawn M. , Rocheleau Jonathan V.
Published: April 2022

We previously showed that pancreatic beta-cells plated on laminin matrix express reduced levels of FGFR1, a receptor linked to beta-cell metabolism and differentiation. Due to recent evidence that adult beta-cells also express FGFR5, a co-receptor for FGFR1, we now aim to determine the effect of laminin on FGFR5 expression and consequent effects on beta-cell metabolism. Using a genetically encoded sensor for NADPH/NADP+ redox state (Apollo-NADP+), we show overexpression of FGFR5 enhances glucose-stimulated NADPH metabolism in beta-cell lines as well as mouse and human beta-cells. This enhanced response was accompanied by increased insulin secretion as well as increased expression of transcripts for glycolytic enzymes (Glucokinase/GCK, PKM2) and the functional maturity marker Urocortin 3 (UCN3). Culturing beta-cells on laminin matrix also stimulated upregulation of endogenous FGFR5 expression, and similarly enhanced beta-cell glucose-stimulated NADPH-metabolism as well as GCK and PKM2 transcript expression. The metabolism and transcript responses triggered by laminin were disrupted by R5ΔC, a truncated receptor isoform that inhibits the FGFR5/FGFR1 signaling complex. Collectively these data reveal that beta-cells respond to laminin by increasing FGFR5 expression to enhance beta-cell glucose metabolism.
Behavioural and neural indices of perceptual decision-making in autistic children during visual motion tasks
Authors: Manning Catherine , Hassall Cameron D. , Hunt Laurence T. , Norcia Anthony M. , Wagenmakers Eric-Jan , Evans Nathan J. , Scerif Gaia
Published: April 2022

Many studies report atypical responses to sensory information in autistic individuals, yet it is not clear which stages of processing are affected, with little consideration given to decision-making processes. We combined diffusion modelling with high-density EEG to identify which processing stages differ between 50 autistic and 50 typically developing children aged 6–14 years during two visual motion tasks. Our pre-registered hypotheses were that autistic children would show task-dependent differences in sensory evidence accumulation, alongside a more cautious decision-making style and longer non-decision time across tasks. We tested these hypotheses using hierarchical Bayesian diffusion models with a rigorous blind modelling approach, finding no conclusive evidence for our hypotheses. Using a data-driven method, we identified a response-locked centro-parietal component previously linked to the decision-making process. The build-up in this component did not consistently relate to evidence accumulation in autistic children. This suggests that the relationship between the EEG measure and diffusion-modelling is not straightforward in autistic children. Compared to a related study of children with dyslexia, motion processing differences appear less pronounced in autistic children. Exploratory analyses also suggest weak evidence that ADHD symptoms moderate perceptual decision-making in autistic children.
The Polyscore of autonomic parameters predicts mortality and identifies low-risk individuals among diabetic survivors of acute myocardial infarction
Authors: Steger Alexander , Dommasch Michael , Müller Alexander , Barthel Petra , Sinnecker Daniel , Wieg Larissa , Hapfelmeier Alexander , Heidegger Helene Hildegard , Huster Katharina Maria , Martens Eimo , Laugwitz Karl-Ludwig , Schmidt Georg , Dirschinger Ralf
Published: April 2022

Survivors of an acute myocardial infarction with diabetes mellitus retain an increased mortality risk. Reliable assessment of individual risk is required for effective and cost-efficient medical care in these patients. The Polyscore is a previously established risk predictor consisting of seven autonomic tests derived from electrocardiogram, blood pressure, and respiration. The Polyscore allows classification of survivors of myocardial infarction in groups at low, intermediate and high mortality risk. The aim of this study was to investigate the prognostic value of the Polyscore in diabetic survivors of acute myocardial infarction, which may be impaired by the presence of diabetic autonomic neuropathy. Survivors of an acute myocardial infarction were included in a prospective cohort study during hospitalisation due to the index event at two university hospitals in Munich, Germany. The Polyscore was determined from simultaneous non-invasive 30-min recordings of electrocardiogram, continuous arterial blood pressure, and respiration which were performed in all participants. Patients were followed for 5 years. The primary and secondary outcomes were all-cause mortality and cardiac mortality. 184 of 941 enrolled patients (19.6%) suffered from diabetes mellitus. 5-year-mortality was higher in diabetic patients (15.2%) compared to non-diabetic patients (5.8%). A multivariable Cox regression model confirmed the Polyscore as a strong predictor of mortality in diabetic post-MI patients (intermediate risk: HR 6.56, 95% CI 1.61–26.78, p = 0.004, mortality 22.8%; high risk: HR 18.76, 95% CI 4.35–80.98, p < 0.001, mortality 68.8%). There was no interaction between diabetes mellitus and the Polyscore regarding mortality prediction (p = 0.775). Interestingly, in contrast to the groups at intermediate and high risk (73 patients, 39.7%), the Polyscore identified a majority of diabetic patients (111, 60.3%) with a low mortality risk, comparable to that of low-risk non-diabetic patients (3.6% and 2.1%, respectively, p = 0.339). Consistent results were observed for cardiac mortality. This analysis shows that the Polyscore predicts all-cause and cardiac mortality in diabetic survivors of acute myocardial infarction. Within these patients it identifies a large population not affected by the excess mortality associated with diabetes in this setting. Thus, the Polyscore may facilitate risk-adapted follow-up strategies in diabetic survivors of myocardial infarction.
Substrate effect on hydrogen evolution reaction in two-dimensional Mo2C monolayers
Authors: Lee Sujin , Min Byungjoon , Bang Junhyeok
Published: April 2022

The physical and chemical properties of atomically thin two-dimensional (2D) materials can be modified by the substrates. In this study, the substrate effect on the electrocatalytic hydrogen evolution reaction (HER) in 2D Mo2C monolayers was investigated using first principles calculations. The isolated Mo2C monolayer shows large variation in HER activity depending on hydrogen coverage: it has relatively low activity at low hydrogen coverage but high activity at high hydrogen coverage. Among Ag, Au, Cu, and graphene substrates, the HER activity is improved on the Ag and Cu substrates especially at low hydrogen coverage, while the effects of the Au and graphene substrates on the HER activity are insignificant. The improvement is caused by the charge redistribution in the Mo2C layer on the substrate, and therefore the HER activity becomes high for any hydrogen coverage on the Ag and Cu substrates. Our results suggest that, in two-dimensional electrocatalysis, the substrate has a degree of freedom to tune the catalytic activity.
Mapping riparian zone macro litter abundance using combination of optical and thermal sensor
Authors: Ramdani Fatwa , Sianturi Riswan Septriayadi , Furqon Muhammad Tanzil , Ananta Mahardeka Tri
Published: April 2022

A significant increase in the world's population will lead to an increase in consumption and, therefore, an increase in global waste. Various attempts have been made to monitor and map waste, but the proposed approaches are difficult and complicated, and they incur high costs. In this study, to overcome limitations in monitoring and mapping plastic waste, using combined optical and thermal sensors installed on drones is proposed. The study area is the riparian zone, or the zone around the river, where the accumulation of plastic waste at the mouth of the river eventually reaches the sea. The image data obtained were processed using machine learning methods to produce high accuracy and precision. To determine the effectiveness of the proposed method, an accuracy assessment was conducted. The results of this study indicate that the combination of optical and thermal sensors provides the best accuracy compared to using only single optical or thermal image data.
Design of an ultra-wideband omnidirectional and polarization insensitive flower petal antenna for potential ambient electromagnetic energy harvesting applications
Authors: Wang Wei-Chih , Garu Prabir
Published: April 2022

Developing a polarization insensitive, omnidirectional, and ultra-wideband (UWB) antenna is highly desired for improving the utilization of freely available electromagnetic (EM) radiation energy. In this study, we have designed an UWB antenna based on tapered flower petals and numerically analyzed to show that it is a promising candidate for energy harvesting applications in the infrared (IR) to UV–visible regime. The impacts of design strategy and parameters on the absorption performance are studied numerically. The antenna shows a high performance in both bandwidth and absorptivity (average absorption of 84.5% spanning a broad range from 25 to 800 THz) under normal incidence of plane waves. To get a better understanding behind such high and UWB absorption mechanism, we investigated the electric field (E-field) distribution over the structure. The antenna also generates less than 5% absorption deviation between normal to 45° incident angle and 0.05% absorption deviation between 0° and 90° polarizations for both transverse electric (TE) and transverse magnetic (TM) modes. This new design aspect and the numerical findings unfolds the new direction for numerous EM wideband applications such as THz technology, photo detection, bolometric sensing, camouflaging, spectral imaging, and ambient EM energy harvesting applications.
PET imaging of mitochondrial function in acute doxorubicin-induced cardiotoxicity: a proof-of-principle study
Authors: Detmer Felicitas J. , Alpert Nathaniel M. , Moon Sung-Hyun , Dhaynaut Maeva , Guerrero J. Luis , Guehl Nicolas J. , Xing Fangxu , Brugarolas Pedro , Shoup Timothy M. , Normandin Marc D. , Pelletier-Galarneau Matthieu , El Fakhri Georges , Petibon Yoann
Published: April 2022

Mitochondrial dysfunction plays a key role in doxorubicin-induced cardiotoxicity (DIC). In this proof-of-principle study, we investigated whether PET mapping of cardiac membrane potential, an indicator of mitochondrial function, could detect an acute cardiotoxic effect of doxorubicin (DOX) in a large animal model. Eight Yucatan pigs were imaged dynamically with [18F](4-Fluorophenyl)triphenylphosphonium ([18F]FTPP+) PET/CT. Our experimental protocol included a control saline infusion into the left anterior descending coronary artery (LAD) followed by a DOX test infusion of either 1 mg/kg or 2 mg/kg during PET. We measured the change in total cardiac membrane potential (ΔΨT), a proxy for the mitochondrial membrane potential, ΔΨm, after the saline and DOX infusions. We observed a partial depolarization of the mitochondria following the DOX infusions, which occurred only in myocardial areas distal to the intracoronary catheter, thereby demonstrating a direct association between the exposure of the mitochondria to DOX and a change in ΔΨT. Furthermore, doubling the DOX dose caused a more severe depolarization of myocardium in the LAD territory distal to the infusion catheter. In conclusion, [18F]FTPP+ PET-based ΔΨT mapping can measure partial depolarization of myocardial mitochondria following intracoronary DOX infusion in a large animal model.
Early menopause is associated with increased risk of retinal vascular occlusions: a nationwide cohort study
Authors: Hwang Sungsoon , Kang Se Woong , Choi Kyung Jun , Son Ki Young , Lim Dong Hui , Shin Dong Wook , Choi DooSeok , Kim Sang Jin
Published: April 2022

This nationwide population-based cohort study evaluated the association between female reproductive factors and the incidence of retinal vein occlusion (RVO) and retinal artery occlusion (RAO) using data provided by the Korea National Health Insurance Service. A total of 2,289,347 postmenopausal women over 50 years of age who participated in both national health screening and cancer screening in 2013 or 2014 were included. Data on female reproductive factors, including age at menarche, age at menopause, parity, history of hormone replacement therapy, and oral contraceptive pill usage, were collected. Patients were followed up until December 2018, and incident cases of RVO and RAO were identified using registered diagnostic codes from claim data. During an average follow-up period of 4.90 years, 7461 and 1603 patients were newly diagnosed with RVO and RAO, respectively. In the multivariable-adjusted Cox proportional hazard model, patients who experienced menopause after 55 years of age had a lower risk of RVO and RAO development compared to those who had menopause before 45 years of age, with a hazard ratio (95% confidence interval) of 0.83 (0.76–0.95) for RVO and 0.80 (0.66‒0.98) for RAO. In conclusion, early menopause was an independent risk factor for future development of RVO and RAO.
Direct effects of elevated dissolved CO2 can alter the life history of freshwater zooplankton
Authors: Ramaekers Lana , Pinceel Tom , Brendonck Luc , Vanschoenwinkel Bram
Published: April 2022

Dissolved CO2 levels (pCO2) are increasing in lentic freshwaters across the globe. Recent studies have shown that this will impact the nutritional quality of phytoplankton as primary producers. However, the extent to which freshwater zooplankton may also be directly affected remains unclear. We test this in three model species representative of the main functional groups of primary consumers in freshwaters; the water flea Daphnia magna, the seed shrimp Heterocypris incongruens and the rotifer Brachionus calyciflorus. We experimentally exposed individuals to three pCO2 levels (1,500; 25,500 and 83,000 ppm) to monitor changes in life history in response to current, elevated and extreme future pCO2 conditions in ponds and shallow lakes. All species had reduced survival under the extreme pCO2 treatment, but the water flea was most sensitive. Body size and reproduction were reduced at 25,500 ppm in the water flea and the seed shrimp and population growth was delayed in the rotifer. Overall, our results show that direct effects of pCO2 could impact the population dynamics of freshwater zooplankton. By differentially modulating the life history of functional groups of primary consumers, elevated pCO2 has the potential to change the evolutionary trajectories of populations as well as the ecological functioning of freshwater communities.