bluuebunny/crossref_metadata_2025 huggingface dataset:
Injection‐Induced Seismicity Size Distribution Dependent on Shear Stress
Authors: Mukuhira Y. , Fehler M. C. , Ito T. , Asanuma H. , Häring M. O.
Published: March 2021

Like natural seismicity, induced seismicity caused by injection also shows a power law size distribution, and its gradient b‐value is used for seismic hazard analysis. Despite the well‐known result that b‐value is negatively correlated with differential stress for natural earthquakes, there is no similar correlation for b‐value variations because the differential stress is nearly constant for injection‐induced seismicity, we thus investigate the b‐value dependence on the relative shear stress acting on existing fractures, using the fault orientation and in situ stress information. The seismicity occurring along existing fractures having high shear stress has significantly lower b‐values than does that associated with lower shear stress fractures. We examine the b‐value dependency on slightly changing differential stress, but the relationship is not clear. The b‐value for injection‐induced seismicity is dependent on relative shear stress on faults, which is a novel physical explanation for the b‐value variations of induced seismicity.
Anisotropy Gradients in the Middle of the Ross Sea Embayment, West Antarctica: Evidence From QL Scattered Surface Waves
Authors: Cheng W. , Hu X. G. , Liu L. T.
Published: March 2021

Long‐period quasi‐Love (QL) waves in West Antarctica were detected using the band‐pass filtering. Rayleigh waves from March 11, 2011 Tohoku Mw 9.1 earthquake and March 9, 2011 Tohoku Mw 7.3 earthquake had evident QL waves in the frequency range of 7–13 mHz when crossing the Ross Sea Embayment (RSE), while exhibiting normal behavior when crossing the Southern Ocean adjacent to the RSE. We located an anisotropic boundary in the upper mantle beneath the RSE according to the QL waves. Surprisingly, the boundary was consistent with the sharp transition zone of magnetic anomalies discovered by the most recent airborne magnetic surveys. Thus, we speculate that the anisotropic boundary was most likely due to vertical mantle flow below the RSE, which may provide evidence of a vertically coherent boundary condition in the RSE. That anisotropic boundary may be an important tectonic imprint for maintaining the stability of the Ross Ice Shelf.
Retreat of Humboldt Gletscher, North Greenland, Driven by Undercutting From a Warmer Ocean
Authors: Rignot Eric , An Lu , Chauche Nolwenn , Morlighem Mathieu , Jeong Seongsu , Wood Michael , Mouginot Jeremie , Willis Josh K. , Klaucke Ingo , Weinrebe Wilhelm , Muenchow Andreas
Published: March 2021

Humboldt Gletscher is a 100‐km wide, slow‐moving glacier in north Greenland which holds a 19‐cm global sea level equivalent. Humboldt has been the fourth largest contributor to sea level rise since 1972 but the cause of its mass loss has not been elucidated. Multi‐beam echo sounding data collected in 2019 indicate a seabed 200 m deeper than previously known. Conductivity temperature depth data reveal the presence of warm water of Atlantic origin at 0°C at the glacier front and a warming of the ocean waters by 0.9 ± 0.1°C since 1962. Using an ocean model, we reconstruct grounded ice undercutting by the ocean, combine it with calculated retreat caused by ice thinning to floatation, and are able to fully explain the observed retreat. Two thirds of the retreat are caused by undercutting of grounded ice, which is a physical process not included in most ice sheet models.
The Cushion Region and Dayside Magnetodisc Structure at Saturn
Authors: Staniland N. R. , Dougherty M. K. , Masters A. , Achilleos N.
Published: March 2021

A sustained quasi‐dipolar magnetic field between the current sheet outer edge and the magnetopause, known as a cushion region, has previously been observed at Jupiter, but not yet at Saturn. Using the complete Cassini magnetometer data, the first evidence of a cushion region forming at Saturn is shown. Only five examples of a sustained cushion are found, revealing this phenomenon to be rare. Four of the cushion regions are identified at dusk and one pre‐noon. It is suggested that greater heating of plasma post‐noon coupled with the expansion of the field through the afternoon sector makes the disc more unstable in this region. These results highlight a key difference between the Saturn and Jupiter systems.
Sub‐Cloud Turbulence Explains Cloud‐Base Updrafts for Shallow Cumulus Ensembles: First Observational Evidence
Authors: Zheng Youtong , Rosenfeld Daniel , Li Zhanqing
Published: March 2021

Sub‐cloud turbulent kinetic energy has been used to parameterize the cloud‐base updraft velocity (wb) in cumulus parameterizations. The validity of this idea has never been proved in observations. Instead, it was challenged by recent Doppler Lidar observations showing a poor correlation between the two. We argue that the low correlation is likely caused by the difficulty of a fixed‐point Lidar to measure ensemble properties of cumulus fields. Taking advantage of the stationarity and ergodicity of early afternoon convection, we developed a Lidar sampling methodology to measure wb of a shallow cumulus (ShCu) ensemble (not a single ShCu). By analyzing 128 ShCu ensembles over the Southern Great Plains, we show that the ensemble properties of sub‐cloud turbulence explain nearly half of the variability in ensemble‐mean wb, demonstrating the ability of sub‐cloud turbulence to dictate wb. The derived empirical formulas will be useful for developing cumulus parameterizations and satellite inference of wb.
The Climate Response to Emissions Reductions Due to COVID‐19: Initial Results From CovidMIP
Authors: Jones Chris D. , Hickman Jonathan E. , Rumbold Steven T. , Walton Jeremy , Lamboll Robin D. , Skeie Ragnhild B. , Fiedler Stephanie , Forster Piers M. , Rogelj Joeri , Abe Manabu , Botzet Michael , Calvin Katherine , Cassou Christophe , Cole Jason N.S. , Davini Paolo , Deushi Makoto , Dix Martin , Fyfe John C. , Gillett Nathan P. , Ilyina Tatiana , Kawamiya Michio , Kelley Maxwell , Kharin Slava , Koshiro Tsuyoshi , Li Hongmei , Mackallah Chloe , Müller Wolfgang A. , Nabat Pierre , van Noije Twan , Nolan Paul , Ohgaito Rumi , Olivié Dirk , Oshima Naga , Parodi Jose , Reerink Thomas J. , Ren Lili , Romanou Anastasia , Séférian Roland , Tang Yongming , Timmreck Claudia , Tjiputra Jerry , Tourigny Etienne , Tsigaridis Kostas , Wang Hailong , Wu Mingxuan , Wyser Klaus , Yang Shuting , Yang Yang , Ziehn Tilo
Published: March 2021

Many nations responded to the corona virus disease‐2019 (COVID‐19) pandemic by restricting travel and other activities during 2020, resulting in temporarily reduced emissions of CO2, other greenhouse gases and ozone and aerosol precursors. We present the initial results from a coordinated Intercomparison, CovidMIP, of Earth system model simulations which assess the impact on climate of these emissions reductions. 12 models performed multiple initial‐condition ensembles to produce over 300 simulations spanning both initial condition and model structural uncertainty. We find model consensus on reduced aerosol amounts (particularly over southern and eastern Asia) and associated increases in surface shortwave radiation levels. However, any impact on near‐surface temperature or rainfall during 2020–2024 is extremely small and is not detectable in this initial analysis. Regional analyses on a finer scale, and closer attention to extremes (especially linked to changes in atmospheric composition and air quality) are required to test the impact of COVID‐19‐related emission reductions on near‐term climate.
Auroral‐Enhanced Plasma Lines by Suprathermal Electrons Observed by EISCAT
Authors: Feng Ting , Liu Moran , Xu Bin , Xu Tong , Gao Shuaihe , Wang Xiang , Zhou Chen
Published: March 2021

Plasma lines (PLs) observed by the European Incoherent Scatter Scientific Association (EISCAT) incoherent scatter radar (ISR) data set during the recent solar maximum 2014 are investigated. To statistically analyze the PLs in the EISCAT data set, we develop an algorithm for the automatic extraction of naturally enhanced PLs from the ISR spectra. Two typical types of auroral‐enhanced PLs at high latitude, namely, secondary electron and electron beam, are analyzed based on this PL extraction algorithm. Our results show that PL enhancements originating from secondary electrons and electron beams present evident magnetic local time dependence. Moreover, the statistical study indicates that the PL enhancements are correlated with the geomagnetic and solar activities. These results can provide insights into solar wind‐magnetosphere‐ionosphere coupling mechanisms.
Recent Advances of a Box Model to Represent the Estuarine Dynamics: Time‐Variable Estuary Length and Eddy Diffusivity
Authors: Verri Giorgia , Mahmoudi Kurdistani Sahameddin , Coppini Giovanni , Valentini Andrea
Published: March 2021

This study starts from a two‐layer 1D Estuary Box Model (EBM), the so called Centro Euro‐Mediterraneo sui Cambiamenti Climatici (CMCC) EBM (Verri et al., 2020, https://doi.org/10.1016/j.ocemod.2020.101587), devised to offer a proper representation of the net river release in a coupled modeling framework with hydrology models and ocean models reaching the mesoscale. Two key advances are proposed in the present study: (I) the estuary length and (II) the horizontal eddy diffusivity coefficient are no longer considered as static parameters to calibrate but two non‐dimensional equations have been introduced in order to make them time‐variable. The Goro branch of the Po river delta is considered as case study of “salt‐wedge estuary” flowing into a microtidal sea. Regarding the estuary length, a non‐dimensional equation has been tested and validated. This equation provides a time dependent estuary box volume which is more realistic choice. This time‐variable estuary length represents the length of the salt wedge intrusion. Regarding the horizontal eddy diffusivity, the static eddy coefficient adopted in the previous version of the model is a coarse assumption. Thus a non‐dimensional equation for this coefficient has been tested and validated. It makes the eddy diffusivity dependent on the velocity shear, the salinity gradient and the estuary geometry. The proposed dynamic formula is found to enhance the model capability to reproduce the salinity at the estuary mouth. Overall the high statistical performance in terms of RMSE and correlation coefficient, the short CPU time and the minimal calibration encourage to use the CMCC EBM in coupled mode with both mesoscale‐resolving ocean and hydrology models to produce operational forecasts and climate scenarios.
Using a Paired Chironomid δ18O and Aquatic Leaf Wax δ2H Approach to Reconstruct Seasonality on Western Greenland During the Holocene
Authors: Corcoran Megan C. , Thomas Elizabeth K. , Morrill Carrie
Published: March 2021

The Arctic hydrological cycle is predicted to intensify as the Arctic warms, due to increased poleward moisture transport during summer and increased evaporation from seas once ice‐covered during winter. Records of past Arctic precipitation seasonality are important because they provide a context for these ongoing changes. In some Arctic lakes, stable isotopes of oxygen and hydrogen (δ18O and δ2H, respectively) vary seasonally, due to seasonal changes in precipitation δ18O and δ2H. We reconstruct precipitation seasonality from Lake N3, a well‐dated lake sediment archive in Disko Bugt, western Greenland, by generating Holocene records of two proxies that are produced at different times of the year, and therefore record different lake water seasonal isotopic compositions. Aquatic plants synthesize waxes throughout the summer, and their δ2H reflects winter‐biased precipitation δ2H at Lake N3, whereas chironomids synthesize their head capsules between late summer and winter, and their δ18O reflects summer‐biased precipitation δ18O at Lake N3. During the middle Holocene at Lake N3, aquatic plant leaf wax was strongly 2H‐depleted, while chironomid chitin was 18O‐enriched. We guide interpretations of these records using sensitivity tests of a lake water and energy balance model, where we change precipitation amount and isotope seasonality inputs. The sensitivity tests suggest that the contrasting trends between proxies were likely caused by an increase in precipitation amount during all seasons and an increase in precipitation isotope seasonality, in addition to proxy‐specific mechanisms, highlighting the importance of understanding lake‐ and proxy‐specific systematics when interpreting records from sediment archives.
Development and Evaluation of an ODE Representation of 3D Subsurface Tile Drainage Flow Using the HLM Flood Forecasting System
Authors: Fonley M. R. , Qiu K. , Velásquez N. , Haut N. K. , Mantilla R.
Published: March 2021

We developed a new ordinary differential equation (ODE) to represent subsurface flows from a hillslope with artificial subsurface drainage (tiling) into an adjacent channel. Our ODE is based on a derived storage‐discharge relationship from high‐resolutions HYDRUS3D simulations that solve 3D partial differential Richards' equations for a hillslope (plot scale) with internal drainage surfaces, variable soil depth, hydraulic conductivity, and varying slope in the direction of flow. The ODE does not capture the hysteresis in the storage‐drainage relation that can only be captured using partial differential equations (PDEs), however the simplification does not have major impacts on the modeled flows. The nondimensional representation of the equation is consistent with, and provides an explanation for, the empirical equation used in classical hydrological models such as the ARNO (Arno River) and Variable Infiltration Capacity (VIC) model to simulate subsurface flows, which removes the need for parameter calibration. Our equation captures the features not captured by other ODE simplifications such as DRAINMOD. The ODE can be coupled to the Hillslope Link Model (HLM) flood forecasting system allowing real‐time regional simulation of streamflow fluctuations and floods over large domains. We show that (i) the new equation improves the capability to model watershed scale hydrograph recessions and to better capture the timing above flood thresholds for multiple spatial scales from 0.1 to 18,000 km2; (ii)using realistic values of slope combined with typical values of tile separation and soil depth provides good predictive power at gauged basin outlets; and (iii) parameters can be derived for particular situations using the 3D PDE framework.
Combining Hydrologic Simulations and Stream‐network Models to Reveal Flow‐ecology Relationships in a Large Alpine Catchment
Authors: Larsen Stefano , Majone Bruno , Zulian Patrick , Stella Elisa , Bellin Alberto , Bruno Maria Cristina , Zolezzi Guido
Published: March 2021

Flow regimes profoundly influence river organisms and ecosystem functions, but regulatory approaches often lack the scientific basis to support sustainable water allocation. In part, this reflects the challenge of understanding the ecological effects of flow variability over different temporal and spatial domains. Here, we use a process‐based distributed hydrological model to simulate 23 years of natural flow regime in 100 bioassessment sites across the Adige River network (NE Italy), and to identify typical nivo‐glacial, nivo‐pluvial, and pluvial reaches. We then applied spatial stream‐network models (SSN) to investigate the relationships between hydrologic and macroinvertebrate metrics while accounting for network spatial autocorrelation and local habitat conditions. Macroinvertebrate metrics correlated most strongly with summer, winter, and temporal variation in streamflow, but effects varied across flow regime types. For example (i) taxon richness appeared limited by high summer flows and high winter flows in nivo‐glacial and pluvial streams, respectively; (ii) invertebrate grazers increased proportionally with the annual coefficient of flow variation in nivo‐glacial streams but tended to decline with flow variation in pluvial streams. Although local land‐use and water quality also affected benthic communities, most variation in macroinvertebrate metrics was associated with spatial autocorrelation. These findings highlight the importance of developing environmental flow management policies in ways that reflect specific hydro‐ecological and land use contexts. Our analyses also illustrate the importance of spatially‐explicit approaches that account for auto‐correlation when quantifying flow‐ecology relationships.
Comparing Assimilation of Synthetic Soil Moisture Versus C‐Band Backscatter for Hyper‐Resolution Land Surface Modeling
Authors: Sun Leqiang , Belair Stephane , Carrera Marco L. , Bilodeau Bernard , Dabboor Mohammed
Published: March 2021

This paper presents the assimilation of synthetic surface soil moisture retrievals and C‐band backscatter signal in a 100‐meter resolution version of the Canadian Land Data Assimilation System (CaLDAS) on footprint scale soil moisture with a time interval of three hours. The synthetic surface soil moisture map was generated by extrapolating a regression relationship between in situ measurements and open loop land surface model outputs based on the soil texture of a given pixel. The surface roughness was inverted from RADARSAT‐2 imagery using a modified Integral Equation Model (IEM) model. Three hourly synthetic backscatter maps were created from this surface roughness and the synthetic soil moisture. The Ensemble Kalman filter (EnKF) with bias correction was applied to mitigate the impact of nonlinear errors introduced by multi‐sourced perturbations. Both time series and spatial maps were examined in the evaluation of the assimilation experiments. Results show that the assimilation of backscatter is as effective as assimilating soil moisture retrievals although the later has slightly better temporal statistics. Compared to the open loop, both approaches improved the analysis of surface and root zone soil moisture with significantly lower bias. For the later, the open loop average bias was reduced from −1.25 vol/vol to 0.59 vol/vol by backscatter assimilation and to 0.41 vol/vol by soil moisture assimilation.
Thank You to Our 2020 Reviewers
Authors: Balikhin Michael , Hickey Michael , Ganushkina Natalia , Pierrard Viviane , Song Paul , Zong Qiugang
Published: March 2021

Key Points

The editors thank the 2020 peer reviewers
Exovesicular-Shh confers Imatinib resistance by upregulating Bcl2 expression in chronic myeloid leukemia with variant chromosomes
Authors: Anusha  , Dalal Hamza , Subramanian Sitalakshmi , V. P. Snijesh , Gowda Divya A. , H. Krishnamurthy , Damodar Sharat , Vyas Neha
Published: March 2021

Chronic myeloid leukemia (CML) patients with complex chromosomal translocations as well as non-compliant CML patients often demonstrate short-lived responses and poor outcomes on the current therapeutic regimes using Imatinib and its variants. It has been derived so far that leukemic stem cells (LSCs) are responsible for Imatinib resistance and CML progression. Sonic hedgehog (Shh) signaling has been implicated in proliferation of this Imatinib-resistant CD34(+) LSCs. Our work here identifies the molecular mechanism of Shh-mediated mutation-independent Imatinib resistance that is most relevant for treating CML-variants and non-compliant patients. Our results elucidate that while Shh can impart stemness, it also upregulates expression of anti-apoptotic protein—Bcl2. It is the upregulation of Bcl2 that is involved in conferring Imatinib resistance to the CD34(+) LSCs. Sub-toxic doses of Bcl2 inhibitor or Shh inhibitor (<<IC50), when used as adjuvants along with Imatinib, can re-sensitize Shh signaling cells to Imatinib. Our work here highlights the need to molecularly stratify CML patients and implement combinatorial therapy to overcome the current limitations and improve outcomes in CML.
Typing FGFR2 translocation determines the response to targeted therapy of intrahepatic cholangiocarcinomas
Authors: Pu Xiaohong , Ye Qing , Cai Jing , Yang Xin , Fu Yao , Fan Xiangshan , Wu Hongyan , Chen Jun , Qiu Yudong , Yue Shen
Published: March 2021

Chromosomal translocations involving fibroblast growth factor receptor 2 (FGFR2) gene at the breakpoints are common genetic lesions in intrahepatic cholangiocarcinoma (ICC) and the resultant fusion protein products have emerged as promising druggable targets. However, predicting the sensitivity of FGFR2 fusions to FGFR kinase inhibitors is crucial to the prognosis of the ICC-targeted therapy. Here, we report identification of nine FGFR2 translocations out of 173 (5.2%) ICC tumors. Although clinicopathologically these FGFR2 translocation bearing ICC tumors are indistinguishable from the rest of the cohort, they are invariably of the mass-forming type originated from the small bile duct. We show that the protein products of FGFR2 fusions can be classified into three subtypes based on the breaking positions of the fusion partners: the classical fusions that retain the tyrosine kinase (TK) and the Immunoglobulin (Ig)-like domains (n = 6); the sub-classical fusions that retain only the TK domain without the Ig-like domain (n = 1); and the non-classical fusions that lack both the TK and Ig-like domains (n = 2). We demonstrate that cholangiocarcinoma cells engineered to express the classical and sub-classical fusions show sensitivity to FGFR-specific kinase inhibitors as evident by the suppression of MAPK/ERK and AKT/PI3K activities following the inhibitor treatment. Furthermore, the kinase-deficient mutant of the sub-classical fusion also lost its sensitivity to the FGFR-specific inhibitors. Taken together, our study suggests that it is essential to determine the breakpoint and type of FGFR2 fusions in the small bile duct subtype of ICC for the targeted treatment.
Microtubules orchestrate local translation to enable cardiac growth
Authors: Scarborough Emily A. , Uchida Keita , Vogel Maria , Erlitzki Noa , Iyer Meghana , Phyo Sai Aung , Bogush Alexey , Kehat Izhak , Prosser Benjamin L.
Published: March 2021

Hypertension, exercise, and pregnancy are common triggers of cardiac remodeling, which occurs primarily through the hypertrophy of individual cardiomyocytes. During hypertrophy, stress-induced signal transduction increases cardiomyocyte transcription and translation, which promotes the addition of new contractile units through poorly understood mechanisms. The cardiomyocyte microtubule network is also implicated in hypertrophy, but via an unknown role. Here, we show that microtubules are indispensable for cardiac growth via spatiotemporal control of the translational machinery. We find that the microtubule motor Kinesin-1 distributes mRNAs and ribosomes along microtubule tracks to discrete domains within the cardiomyocyte. Upon hypertrophic stimulation, microtubules redistribute mRNAs and new protein synthesis to sites of growth at the cell periphery. If the microtubule network is disrupted, mRNAs and ribosomes collapse around the nucleus, which results in mislocalized protein synthesis, the rapid degradation of new proteins, and a failure of growth, despite normally increased translation rates. Together, these data indicate that mRNAs and ribosomes are actively transported to specific sites to facilitate local translation and assembly of contractile units, and suggest that properly localized translation – and not simply translation rate – is a critical determinant of cardiac hypertrophy. In this work, we find that microtubule based-transport is essential to couple augmented transcription and translation to productive cardiomyocyte growth during cardiac stress.
An ecological network approach to predict ecosystem service vulnerability to species losses
Authors: Keyes Aislyn A. , McLaughlin John P. , Barner Allison K. , Dee Laura E.
Published: March 2021

Human-driven threats are changing biodiversity, impacting ecosystem services. The loss of one species can trigger secondary extinctions of additional species, because species interact–yet the consequences of these secondary extinctions for services remain underexplored. Herein, we compare robustness of food webs and the ecosystem services (hereafter ‘services’) they provide; and investigate factors determining service responses to secondary extinctions. Simulating twelve extinction scenarios for estuarine food webs with seven services, we find that food web and service robustness are highly correlated, but that robustness varies across services depending on their trophic level and redundancy. Further, we find that species providing services do not play a critical role in stabilizing food webs – whereas species playing supporting roles in services through interactions are critical to the robustness of both food webs and services. Together, our results reveal indirect risks to services through secondary species losses and predictable differences in vulnerability across services.
Contact-electrification-activated artificial afferents at femtojoule energy
Authors: Yu Jinran , Gao Guoyun , Huang Jinrong , Yang Xixi , Han Jing , Zhang Huai , Chen Youhui , Zhao Chunlin , Sun Qijun , Wang Zhong Lin
Published: March 2021

Low power electronics endowed with artificial intelligence and biological afferent characters are beneficial to neuromorphic sensory network. Highly distributed synaptic sensory neurons are more readily driven by portable, distributed, and ubiquitous power sources. Here, we report a contact-electrification-activated artificial afferent at femtojoule energy. Upon the contact-electrification effect, the induced triboelectric signals activate the ion-gel-gated MoS2 postsynaptic transistor, endowing the artificial afferent with the adaptive capacity to carry out spatiotemporal recognition/sensation on external stimuli (e.g., displacements, pressures and touch patterns). The decay time of the synaptic device is in the range of sensory memory stage. The energy dissipation of the artificial afferents is significantly reduced to 11.9 fJ per spike. Furthermore, the artificial afferents are demonstrated to be capable of recognizing the spatiotemporal information of touch patterns. This work is of great significance for the construction of next-generation neuromorphic sensory network, self-powered biomimetic electronics and intelligent interactive equipment.
Preclinical efficacy and safety analysis of gamma-irradiated inactivated SARS-CoV-2 vaccine candidates
Authors: Sir Karakus Gozde , Tastan Cihan , Dilek Kancagi Derya , Yurtsever Bulut , Tumentemur Gamze , Demir Sevda , Turan Raife Dilek , Abanuz Selen , Cakirsoy Didem , Seyis Utku , Ozer Samed , Elibol Omer , Elek Muhammer , Ertop Gurcan , Arbak Serap , Acikel Elmas Merve , Hemsinlioglu Cansu , Kocagoz Ayse Sesin , Hatirnaz Ng Ozden , Akyoney Sezer , Sahin Ilayda , Ozbek Ugur , Telci Dilek , Sahin Fikrettin , Yalcin Koray , Ratip Siret , Ovali Ercument
Published: March 2021

COVID-19 outbreak caused by SARS-CoV-2 created an unprecedented health crisis since there is no vaccine for this novel virus. Therefore, SARS-CoV-2 vaccines have become crucial for reducing morbidity and mortality. In this study, in vitro and in vivo safety and efficacy analyzes of lyophilized vaccine candidates inactivated by gamma-irradiation were performed. The candidate vaccines in this study were OZG-3861 version 1 (V1), an inactivated SARS-CoV-2 virus vaccine, and SK-01 version 1 (V1), a GM-CSF adjuvant added vaccine. The candidate vaccines were applied intradermally to BALB/c mice to assess toxicity and immunogenicity. Preliminary results in vaccinated mice are reported in this study. Especially, the vaccine models containing GM-CSF caused significant antibody production with neutralization capacity in absence of the antibody-dependent enhancement feature, when considered in terms of T and B cell responses. Another important finding was that the presence of adjuvant was more important in T cell in comparison with B cell response. Vaccinated mice showed T cell response upon restimulation with whole inactivated SARS-CoV-2 or peptide pool. This study shows that the vaccines are effective and leads us to start the challenge test to investigate the gamma-irradiated inactivated vaccine candidates for infective SARS-CoV-2 virus in humanized ACE2 + mice.
Robotic assisted CyberKnife radiosurgery for the treatment of iris melanoma
Authors: Schmelter Valerie , Heidorn Sarah , Muacevic Alexander , Priglinger Siegfried G. , Foerster Paul , Liegl Raffael
Published: March 2021

Iris melanoma is a rare form of uveal melanoma with potential metastic spread. Treatment options include surgical resection, enucleation or irradiation. We analysed visual outcome, complication appearance and management in eight patients with iris melanoma following robotic-assisted CyberKnife treatment. Consecutive patients from the Department of Ophthalmology at University of Munich were included in the study if they had an iris melanoma that was treated with CyberKnife and had a minimum follow-up of 12 months. We evaluated tumor thickness, largest diameter, visual acuity and complications. 8 patients were included in this report. The median age was 74 years (range: 53–86 years). The median follow-up was 23 months (range 12–48 months). Tumor thickness decreased from 2.1 to 1.4 mm on average. Four out of eight patients showed stable or increased visual acuity compared to visual acuity at first visit. We did not find a correlation of applied radiation volume or radiation dose on visual outcome. Radiation keratopathy was the most common complication in five patients. No recurrences were noted. Robotic-assisted radiosurgery following CyberKnife is a promising non-invasive, single session treatment option for iris melanoma with comparable results regarding recurrence rate or complications to brachytherapy and proton beam therapy. All included patients showed good visual outcome.
Changes of antibiotic prescribing pattern and its resistance to E. Coli in South Korea: a 12-year retrospective observational study
Authors: Lee Geun Woo , Ryu Sukhyun , Park Juhee , Lee Eun Jee , Lee Kwang Jun , Tae Jungyeon , Hwang Youngsik , Kim Dong-Sook
Published: March 2021

In the present study, we investigated the pattern of changes in antibiotic prescription and antimicrobial resistance (AMR) in Escherichia coli in South Korea between 2007 and 2018. We collected data related to antibiotic prescription and AMR in E. coli from the national surveillance system. We used the Mann–Kendall test and Spearman’s correlation to identify the trends of antibiotic prescription and AMR in E. coli and to examine the relationship between them, respectively. Although we noted a significant decreasing trend of ampicillin and gentamicin prescriptions in all medical institutions, we identified a higher level of AMR in long-term care facilities than in other medical institutions. We did not identify a significant positive correlation between ampicillin and gentamicin prescriptions and their resistance in E. coli. However, we found a significant positive correlation between cefotaxime prescription and its resistance in E. coli in hospitals, long-term care facilities, and clinics. Our results strongly suggest that long-term care facilities in South Korea have the potential to sustain AMR epidemics and that more efforts are needed to curb AMR in E. coli. Further epidemiological studies using enhanced AMR surveillance are warranted.
Visibility graph based temporal community detection with applications in biological time series
Authors: Zheng Minzhang , Domanskyi Sergii , Piermarocchi Carlo , Mias George I.
Published: March 2021

Temporal behavior is an essential aspect of all biological systems. Time series have been previously represented as networks. Such representations must address two fundamental problems on how to: (1) Create appropriate networks to reflect the characteristics of biological time series. (2) Detect characteristic dynamic patterns or events as network temporal communities. General community detection methods use metrics comparing the connectivity within a community to random models, or are based on the betweenness centrality of edges or nodes. However, such methods were not designed for network representations of time series. We introduce a visibility-graph-based method to build networks from time series and detect temporal communities within these networks. To characterize unevenly sampled time series (typical of biological experiments), and simultaneously capture events associated to peaks and troughs, we introduce the Weighted Dual-Perspective Visibility Graph (WDPVG). To detect temporal communities in individual signals, we first find the shortest path of the network between start and end nodes, identifying high intensity nodes as the main stem of our community detection algorithm that act as hubs for each community. Then, we aggregate nodes outside the shortest path to the closest nodes found on the main stem based on the closest path length, thereby assigning every node to a temporal community based on proximity to the stem nodes/hubs. We demonstrate the validity and effectiveness of our method through simulation and biological applications.
In vivo kinematics and cruciate ligament forces in bicruciate-retaining total knee arthroplasty
Authors: Kono Kenichi , Inui Hiroshi , Tomita Tetsuya , Yamazaki Takaharu , Konda Shoji , Taketomi Shuji , Tanaka Sakae , D’Lima Darryl D.
Published: March 2021

We analyzed the effects of bicruciate-retaining total knee arthroplasty (BCR-TKA) on knee kinematics and cruciate ligament forces. Patients (N = 15) with osteoarthritis (OA) and an intact anterior cruciate ligament (ACL) underwent magnetic resonance imaging and single-plane fluoroscopy to measure tibiofemoral kinematics during two deep knee bend activities before and after BCR-TKA: (1) weight-bearing squat; (2) non-weight-bearing cross-legged sitting. Forces in ligament bundles were calculated using VivoSim. The dynamic range of varus-valgus angulation decreased from 3.9 ± 4.4° preoperatively to 2.2 ± 2.7° postoperatively. Preoperatively, the medial femoral condyle translated anteriorly from 10° to 50° of flexion, and posteriorly beyond 50° of flexion. Postoperatively, the medial and lateral femoral condyles translated posteriorly throughout flexion in a medial pivot pattern. ACL forces were high in extension and decreased with flexion pre- and postoperatively. PCL forces increased with flexion preoperatively and did not change significantly postoperatively. Preoperatively, ACL forces correlated with anteroposterior translation of the femoral condyles. Postoperatively, PCL forces correlated with anteroposterior translation of the lateral femoral condyle. BCR-TKA altered knee kinematics during high flexion activity which correlated significantly with changes in cruciate ligament forces.
How mountains and elevations shape the spatial distribution of beetles in Peninsular Malaysia
Authors: Musthafa Muneeb M. , Abdullah Fauziah , Martínez-Falcón Ana Paola , de Bruyn Mark
Published: March 2021

This study was conducted to assess the spatial distribution of beetles in mountain ecosystems and their elevational diversity. Malaise, pitfall and light traps were used to collect beetles from nine different mountains in Malaysia from September 2014 to September 2016, where from Gunung Angsi, Gunung Belumut, Gunung Basor and Gunung Tebu samples were collected at 500 m and 1000 m (above sea level) elevations, while beetles were sampled at 500 m, 1000 m and 1500 masl from Gunung Benom, Gunung Inas, Cameron Highland, Gunung Besar Hantu and Gunung Basor. In this study, 9628 beetles belonging to 879 different species were collected with highest representation from family Staphylinidae and Carabidae. Chamah Highland had the highest beetle diversity followed by Gunung Benom, Gunung Inas, Cameron Highland, Gunung Belumut, and Gunung Basor. Chamah Highland was different to all mountains on abundance and species richness. The highest species richness was observed at 1000 m, followed by 500 m and 1500 m. We identified characteristic species associated with habitat conditions at Gunung Benoum and Gunung Inas mountains, according to INDVAL values. The beetle diversity of the sampled mountains showed multiple alpha and beta patterns according to type of mountain ecosystem and elevation, providing guidelines for the scientific community to underpin conservation efforts in Malaysia.
Presence of tophi is associated with a rapid decline in the renal function in patients with gout
Authors: Oh Yoon-Jeong , Moon Ki Won
Published: March 2021

We aimed to compare clinical characteristics of patients with and without tophi at the time of the diagnosis of gout and investigate the association of tophi and renal function in gout patients. The patients who were first diagnosed with gout at the Kangwon National University Hospital were retrospectively studied. Patients were divided into 2 groups according to the presence of tophi at the diagnosis. We compared clinical characteristics and the progression of renal dysfunction between the two groups. Of 276 patients, 66 (25.5%) initially presented with tophi. Tophi group was older, had a longer symptom duration, and a higher prevalence of multiple joint involvement than those without tophi. In multivariate logistic regression analysis, prolonged symptom duration and multiple joint involvement were significantly associated with increased risk of formation of tophi. The decline in the eGFR was more prominent in patients with tophi than in those without (− 4.8 ± 14.5 vs. − 0.7 ± 11.9 ml/min/1.73 m2/year, respectively; P = 0.039). The presence of tophi was significantly associated with a rapid decline in the eGFR (β = − 0.136; P = 0.042). In conclusion, the presence of tophi was associated with a rapid declining renal function. Therefore, an early diagnosis and closely monitoring of renal function might be important in gout patients with tophi.
Influence of force volume indentation parameters and processing method in wood cell walls nanomechanical studies
Authors: Normand Aubin C. , Charrier Anne M. , Arnould Olivier , Lereu Aude L.
Published: March 2021

Since the established correlations between mechanical properties of a piece of wood at the macroscopic scale and those of the cell wall at the submicron scale, techniques based on atomic force microscopy (AFM) have become widespread. In particular Peak Force tapping, allowing the differentiation of various layers, has become the new standard for wood cell wall’s nanomechanical characterization. However, its use requires fully elastic indentation, a good knowledge of stiffness of the probe and assumes a perfect tip shape of known radius (sphere) or angle (cone). Those strong hypotheses can result in large approximations in the extracted parameters for complex, nanostructured, and stiff and viscous materials such as wood. In this work, we propose a reliable and complementary alternative based on AFM force-volume indentation by refining the Oliver and Pharr nanoindentation processing and calibration procedure for AFM cantilever and tip. The introduced area-function calibration (AFC) method allows to considerably reduce these approximations and provides semi-quantitative measurements. No prior knowledge of the tip shape and cantilever stiffness are required and viscoplasticity is investigated through a qualitative index. Indentation parameters variations are shown to impact the resulting measurements, i.e., indentation modulus, viscoplasticity index, adhesion force and energy. AFC method, applied to map regions of tension wood, provides very stable mechanical parameters characteristic of each region, which makes this method of high interest for plant cell wall studies.
Photonic-plasmonic mode coupling in nanopillar Ge-on-Si PIN photodiodes
Authors: Augel Lion , Schlipf Jon , Bullert Sergej , Bürzele Sebastian , Schulze Jörg , Fischer Inga A.
Published: March 2021

Incorporating group IV photonic nanostructures within active top-illuminated photonic devices often requires light-transmissive contact schemes. In this context, plasmonic nanoapertures in metallic films can not only be realized using CMOS compatible metals and processes, they can also serve to influence the wavelength-dependent device responsivities. Here, we investigate crescent-shaped nanoapertures in close proximity to Ge-on-Si PIN nanopillar photodetectors both in simulation and experiment. In our geometries, the absorption within the devices is mainly shaped by the absorption characteristics of the vertical semiconductor nanopillar structures (leaky waveguide modes). The plasmonic resonances can be used to influence how incident light couples into the leaky modes within the nanopillars. Our results can serve as a starting point to selectively tune our device geometries for applications in spectroscopy or refractive index sensing.
Mercury spikes as evidence of extended arc-volcanism around the Devonian–Carboniferous boundary in the South Tian Shan (southern Uzbekistan)
Authors: Rakociński Michał , Pisarzowska Agnieszka , Corradini Carlo , Narkiewicz Katarzyna , Dubicka Zofia , Abdiyev Nuriddin
Published: March 2021

Recently, the end-Devonian mass extinction (Hangenberg Crisis, 359 Ma) was identified as a first-order mass extinction, albeit not one of the “Big Five” events. Many marine and terrestrial organisms were affected by this crisis. The cause of this mass extinction is still conjectural and widely discussed. Here we report anomalously high mercury (Hg) concentrations from the South Tian Shan (Uzbekistan), together with correlation using conodont biostratigraphic data. Hg enrichment (to 5825 ppb) was detected in marine deposits encompassing the Hangenberg Crisis. In the Novchomok section, the Hangenberg Crisis interval does not contain typical Hangenberg Black Shales; however, by means of inorganic geochemistry (enrichment of redox-sensitive elements such as Mo, V, and U) we detected an equivalent level despite the lack of marked facies changes. This is the first record of Hg and Hg/total organic carbon anomalies in marly shales, marls and carbonates that are totally independent of facies changes, implying that volcanism was the most probable cause of the Hangenberg Crisis. This conclusion is confirmed by the presence of a negative δ13C excursion, which may reflect massive release of isotopically light carbon from volcanogenic and thermogenic devolatilization likely combined with increased arc-volcanism activity worldwide at the end of the Devonian.
Hospital-diagnosed infections with Escherichia coli clonal group ST131 are mostly acquired in the community
Authors: Muller Allison , Gbaguidi-Haore Houssein , Cholley Pascal , Hocquet Didier , Sauget Marlène , Bertrand Xavier
Published: March 2021

The worldwide spread of E. coli ST131 has significantly contributed to the dissemination of E. coli producing extended-spectrum β-lactamases (ESBL). In a French University hospital, we assessed the molecular features of ESBL-producing E. coli and identified risk factors in patients for colonization or infection with E. coli ST131. Over a 2-year period (2015–2017), each patient with at least one clinical isolate or one screening isolate positive with ESBL-producing E. coli were included (n = 491). The ST131 clonal group accounted for 17.5% (n = 86) of all ESBL-producing E. coli and represented 57.3% isolates of phylogroup B2. FimH-based sub-typing showed that 79.1% (68/86) of ST131 isolates were fimH30, among which 67.6% (n = 46), 20.6% (n = 14) and 11.8% (n = 8) isolates harbored genes encoding the ESBL CTX-M-15, CTX-M-27, and CTX-M-14, respectively. The multivariate analysis identified two factors independently associated with ST131 ESBL-producing E. coli isolates: infection (Odds ratio [OR] = 1.887, 95% confidence interval [CI]: 1.143–3.115; p = 0.013) and community acquisition (OR = 2.220, 95% CI: 1.335–3.693; p = 0.002). In conclusion, our study confirmed the predominance of ST131 clonal group among ESBL-producing E. coli and the difficulty to identify common risk factors associated with carriage of this pandemic clonal group.
Differences between two sodium hyaluronate-based submucosal injection materials currently used in Japan based on viscosity analysis
Authors: Hirose Ryohei , Yoshida Takuma , Naito Yuji , Watanabe Naoto , Hashimoto Hikaru , Sugino Satoshi , Bandou Risa , Daidoji Tomo , Inoue Ken , Dohi Osamu , Yoshida Naohisa , Nakaya Takaaki , Itoh Yoshito
Published: March 2021

In Japan, two 0.4% sodium hyaluronate (HA)-based submucosal injection materials (SIMs) are currently used in endoscopic submucosal dissection (ESD): MucoUp (HA-Mc) and Ksmart (HA-Ks). HA-Mc and HA-Ks have the same concentration and are, thus, construed by most endoscopists to have no difference. Nevertheless, visual observation conveys the impression that HA-Ks have a higher viscosity than HA-Mc, suggesting that HA-Ks performs better than HA-Mc. This study aimed to examine the differences between HA-Mc and HA-Ks. HA-Ks exhibited higher viscosity due to greater weight-average molecular weight compared with HA-Mc. HA-Ks had significantly greater submucosal elevation height (SEH) than HA-Mc; the SEH of HA-Ks-80% (80% dilution of HA-Ks) was the same as that of HA-Mc. The ESD procedure time was significantly shorter with HA-Ks than with HA-Mc (15.2 ± 4.1 vs. 19.5 ± 5.9; P = 0.049). The total injection volume for HA-Ks was significantly lower than that for HA-Mc (10.8 ± 3.6 vs. 14.4 ± 4.6; P = 0.045). However, no significant difference in these items was observed between HA-Mc and HA-Ks-80%. HA-Mc and HA-Ks were considered to be almost the same. Nonetheless, HA-Ks exhibited higher viscosity and SIM performance than HA-Mc. HA-Ks-80% had almost the same performance as HA-Mc. Thus, understanding SIM performance and characteristics requires a focus on the viscosity of SIMs.
Singular and short-term anesthesia exposure in the developing brain induces persistent neuronal changes consistent with chronic neurodegenerative disease
Authors: Hogarth Kaley , Vanama Ramesh Babu , Stratmann Greg , Maynes Jason T.
Published: March 2021

The potential adverse impact of inhalational anesthetics on the developing brain was highlighted by the addition of a medication warning by the U.S. Food and Drug Administration for their use in the pediatric population. To investigate mechanisms by which early life anesthesia exposure could induce long-term neuronal dysfunction, we exposed rats to 1 minimum alveolar concentration sevoflurane at 7 days of life. The animals were raised normally until adulthood (P300) prior to sacrifice and analysis of cortical tissue structure (TEM), mitochondrial quality control and biogenesis pathways (Western blot, ELISA, ADP/ATP content), and markers of oxidative stress, proteotoxicity and inflammation (Western blot, ELISA). We found that early life anesthesia exposure led to adverse changes in mitochondrial quality maintenance pathways, autophagy and mitochondrial biogenesis. Although there was an escalation of oxidative stress markers and an increase in the nuclear localization of stress-related transcription factors, cellular redox compensatory responses were blunted, and oxidative phosphorylation was reduced. We found upregulation of mitochondrial stress and proteotoxicity markers, but a significant reduction of mitochondrial unfolded protein response end-effectors, contributing to an increase in inflammation. Contrary to acute exposure, we did not find an increase in apoptosis. Our findings suggest that a limited, early exposure to anesthesia may produce lasting cellular dysfunction through the induction of a sustained energy deficient state, resulting in persistent neuroinflammation and altered proteostasis/toxicity, mimicking aspects of chronic neurodegenerative diseases.