bluuebunny/crossref_metadata_2025 huggingface dataset:
Size‐Fraction‐Specific Stable Isotope Variations as a Framework for Interpreting Early Eocene Bulk Sediment Carbon Isotope Records
Authors: Bhattacharya Joyeeta , Yeung Laurence Y. , Cong Lin , Dickens Gerald R. , Sun Tao
Published: March 2021

Carbon isotope (δ13C) records from marine sediments and sedimentary rocks have been extensively used in Cenozoic chemostratigraphy. The early Paleogene interval in particular has received exceptional attention because negative carbon isotope excursions (CIEs) documented in the sedimentary record, for example, at the Paleocene Eocene Thermal Maximum (PETM), ca ∼56 Ma, are believed to reflect significant global carbon cycle perturbations during the warmest interval of the Cenozoic era. However, while bulk carbonate δ13C values exhibit robust correlations across widely separated marine sedimentary basins, their absolute values and magnitude of CIEs vary spatially, especially over time intervals characterized by major deviations in global carbon cycling. Moreover, bulk carbonates in open‐marine environments are an ensemble of different components, each with a distinct isotope composition. Consequently, a comprehensive interpretation of the bulk‐δ13C record requires an understanding of co‐evolution of these components. In this study, we dissect sediments, from the late Paleocene‐early Eocene interval, at ODP Site 1209 (Shatsky Rise, Pacific Ocean) to investigate how a temporally varying bulk carbonate ensemble influences the overall carbon isotope record. A set of 45 samples were examined for δ13C and δ18O compositions, as bulk and individual size fractions. We find a significant increase in coarse‐fraction abundance across the PETM, driven by a changing community structure of calcifiers, modulating the size of the CIE at Site 1209 and thus making it distinct from those recorded at other open‐marine sites. These results highlight the importance of biogeography in the marine stable isotope record, especially when isotope excursions are driven by climate‐ and/or carbon cycle changes. In addition, community composition changes will alter the interpretation of weight percent coarse fraction as proxy for carbonate dissolution.
Study of the Impact of Past Extreme Solar Events on the Modern Air Traffic
Authors: Hubert G. , Aubry S.
Published: March 2021

The ancient solar energetic particle (SEP) events of 774/775 CE and 993/994 CE were characterized thanks to radionuclide productions stored in environmental archives as ice cores or tree rings. Primary cosmic ray spectra deduced from these cosmogenic isotope data indicate that the impact of these extreme SEP events would have been much more significant than any of the ones observed during the modern era. However, the impact of these should be studied more accurately in the framework of the ambient dose equivalent impacting aircrew and passengers in the air traffic context by considering physical parameters such as time profile or anisotropy properties. In this study, the impact that 774/775 CE and 993/994 CE past extreme SEP events could have had on modern air traffic is discussed. Possible event spectra for these ancient events are derived from the spectra ground‐level enhancement (GLE) 5 and GLE 69, which have been observed during the modern era and have been widely studied/characterized using measurements. The investigations include the impact of the SEP activity on ambient dose equivalent, including detailed analyses considering route, airplane characteristics (departure, arrival, continent, airplane type), and the time occurrence of the SEP event. Statistical analyses show that additional dose levels can reach values on the order of 70 mSv, which is absolutely significant considering the current air traffic recommendations. The orders of magnitude of the ambient dose equivalent induced during past extreme SEP events raises a number of issues, both for aircrews and for avionics hardware. This study demonstrates that simulations can be useful for the evaluation of risks in case of extreme SEP events.
Fill‐and‐Spill: A Process Description of Runoff Generation at the Scale of the Beholder
Authors: McDonnell Jeffrey J. , Spence Christopher , Karran Daniel J. , van Meerveld H. J. (Ilja) , Harman Ciaran J.
Published: March 2021

Descriptions of runoff generation processes continue to grow, helping to reveal complexities and hydrologic behavior across a wide range of environments and scales. But to date, there has been little grouping of these process facts. Here, we discuss how the “fill‐and‐spill” concept can provide a framework to group event‐based runoff generation processes. The fill‐and‐spill concept describes where vertical and lateral additions of water to a landscape unit are placed into storage (the fill)—and only when this storage reaches a critical level (the spill), and other storages are filled and become connected, does a previously infeasible (but subsequently important) outflow pathway become activated. We show that fill‐and‐spill can be observed at a range of scales and propose that future fieldwork should first define the scale of interest and then evaluate what is filling‐and‐spilling at that scale. Such an approach may be helpful for those instrumenting and modeling new hillslopes or catchments because it provides a structured way to develop perceptual models for runoff generation and to group behaviors at different sites and scales.
Thank You to Our 2020 Reviewers
Authors: Fox Peter A. , Altintas Ilkay , Diviacco Paolo , Donnellan Andrea , Gentemann Chelle , Glaves Helen M. , Jiang Jonathan H. , Maute Astrid , Pirenne Benoit , Tiampo Kristy
Published: March 2021

Key Point

The editors thank the 2020 peer reviewers
Biophotonic sensors with integrated Si3N4-organic hybrid (SiNOH) lasers for point-of-care diagnostics
Authors: Kohler Daria , Schindler Gregor , Hahn Lothar , Milvich Johannes , Hofmann Andreas , Länge Kerstin , Freude Wolfgang , Koos Christian
Published: March 2021

Early and efficient disease diagnosis with low-cost point-of-care devices is gaining importance for personalized medicine and public health protection. Within this context, waveguide-(WG)-based optical biosensors on the silicon-nitride (Si3N4) platform represent a particularly promising option, offering highly sensitive detection of indicative biomarkers in multiplexed sensor arrays operated by light in the visible-wavelength range. However, while passive Si3N4-based photonic circuits lend themselves to highly scalable mass production, the integration of low-cost light sources remains a challenge. In this paper, we demonstrate optical biosensors that combine Si3N4 sensor circuits with hybrid on-chip organic lasers. These Si3N4-organic hybrid (SiNOH) lasers rely on a dye-doped cladding material that are deposited on top of a passive WG and that are optically pumped by an external light source. Fabrication of the devices is simple: The underlying Si3N4 WGs are structured in a single lithography step, and the organic gain medium is subsequently applied by dispensing, spin-coating, or ink-jet printing processes. A highly parallel read-out of the optical sensor signals is accomplished with a simple camera. In our proof-of-concept experiment, we demonstrate the viability of the approach by detecting different concentrations of fibrinogen in phosphate-buffered saline solutions with a sensor-length (L-)-related sensitivity of S/L = 0.16 rad nM−1 mm−1. To our knowledge, this is the first demonstration of an integrated optical circuit driven by a co-integrated low-cost organic light source. We expect that the versatility of the device concept, the simple operation principle, and the compatibility with cost-efficient mass production will make the concept a highly attractive option for applications in biophotonics and point-of-care diagnostics.
Quantification of T cell clonality in human T cell leukaemia virus type-1 carriers can detect the development of adult T cell leukaemia early
Authors: Wolf Sonia N. , Haddow Jana , Greiller Claire , Taylor Graham P. , Cook Lucy B. M. , Rowan Aileen G.
Published: March 2021

Adult T cell leukaemia/lymphoma (ATL) arises from clonally expanded T cells that are infected with human T cell leukaemia virus type-1 (HTLV-1). Here, we show that ATL can be detected early in HTLV-1-carriers through quantification of T-cell receptor (TCR)Vβ subunit diversity on T-cells infected with HTLV-1 (CD3+ CCR4+ CD26− T-cells) using an ‘oligoclonality index’ (OCI-flow). We established a reference range for OCI-flow by analysing peripheral blood mononuclear cells (PBMCs) from HTLV-1-carriers who had not developed ATL in a median of 10.5 years follow up (n = 38) and patients with ATL (n = 30). In the third cohort of HTLV-1-carriers with no history or clinical evidence of ATL (n = 106), 19% of high proviral load (PVL, ≥4 copies of HTLV-1/100 PBMCs) carriers had an OCI-flow in the ATL range, >0.770. Carriers with an OCI-flow >0.770 (n = 14) had higher lymphocyte counts and PVLs and were more likely to have a family history of ATL than carriers with OCI-flow ≤0.770. ATL subsequently developed in two of these 14 carriers but no carriers with OCI-flow ≤0.770 (p = 0.03, cumulative follow-up 129 person-years). This method can be used to identify a subset of high-PVL HTLV-1-carriers at increased risk of developing ATL who may benefit from intervention therapy, prior to the detection of disease.
E3 ubiquitin ligase Grail promotes hepatic steatosis through Sirt1 inhibition
Authors: Liu Pei-Yao , Chen Cheng-Cheung , Chin Chia-Ying , Liu Te-Jung , Tsai Wen-Chiuan , Chou Jian-Liang , Huang Chuan-Yu , Chen Yu-Guang , Chen Ying-Chuan
Published: March 2021

In obese adults, nonalcoholic fatty liver disease (NAFLD) is accompanied by multiple metabolic dysfunctions. Although upregulated hepatic fatty acid synthesis has been identified as a crucial mediator of NAFLD development, the underlying mechanisms are yet to be elucidated. In this study, we reported upregulated expression of gene related to anergy in lymphocytes (GRAIL) in the livers of humans and mice with hepatic steatosis. Grail ablation markedly alleviated the high-fat diet-induced hepatic fat accumulation and expression of genes related to the lipid metabolism, in vitro and in vivo. Conversely, overexpression of GRAIL exacerbated lipid accumulation and enhanced the expression of lipid metabolic genes in mice and liver cells. Our results demonstrated that Grail regulated the lipid accumulation in hepatic steatosis via interaction with sirtuin 1. Thus, Grail poses as a significant molecular regulator in the development of NAFLD.
Interferometric control of magnon-induced nearly perfect absorption in cavity magnonics
Authors: Rao J. W. , Xu P. C. , Gui Y. S. , Wang Y. P. , Yang Y. , Yao Bimu , Dietrich J. , Bridges G. E. , Fan X. L. , Xue D. S. , Hu C.-M.
Published: March 2021

The perfect absorption of electromagnetic waves has promoted many applications, including photovoltaics, radar cloaking, and molecular detection. Unlike conventional methods of critical coupling that require asymmetric boundaries or coherent perfect absorption that require multiple coherent incident beams, here we demonstrate single-beam perfect absorption in an on-chip cavity magnonic device without breaking its boundary symmetry. By exploiting magnon-mediated interference between two internal channels, both reflection and transmission of our device can be suppressed to zero, resulting in magnon-induced nearly perfect absorption (MIPA). Such interference can be tuned by the strength and direction of an external magnetic field, thus showing versatile controllability. Furthermore, the same multi-channel interference responsible for MIPA also produces level attraction (LA)-like hybridization between a cavity magnon polariton mode and a cavity photon mode, demonstrating that LA-like hybridization can be surprisingly realized in a coherently coupled system.
miR-135a-5p mediates memory and synaptic impairments via the Rock2/Adducin1 signaling pathway in a mouse model of Alzheimer’s disease
Authors: Zheng Kai , Hu Fan , Zhou Yang , Zhang Juan , Zheng Jie , Lai Chuan , Xiong Wan , Cui Ke , Hu Ya-Zhuo , Han Zhi-Tao , Zhang Hong-Hong , Chen Jian-Guo , Man Heng-Ye , Liu Dan , Lu Youming , Zhu Ling-Qiang
Published: March 2021

Aberrant regulation of microRNAs (miRNAs) has been implicated in the pathogenesis of Alzheimer’s disease (AD), but most abnormally expressed miRNAs found in AD are not regulated by synaptic activity. Here we report that dysfunction of miR-135a-5p/Rock2/Add1 results in memory/synaptic disorder in a mouse model of AD. miR-135a-5p levels are significantly reduced in excitatory hippocampal neurons of AD model mice. This decrease is tau dependent and mediated by Foxd3. Inhibition of miR-135a-5p leads to synaptic disorder and memory impairments. Furthermore, excess Rock2 levels caused by loss of miR-135a-5p plays an important role in the synaptic disorder of AD via phosphorylation of Ser726 on adducin 1 (Add1). Blocking the phosphorylation of Ser726 on Add1 with a membrane-permeable peptide effectively rescues the memory impairments in AD mice. Taken together, these findings demonstrate that synaptic-related miR-135a-5p mediates synaptic/memory deficits in AD via the Rock2/Add1 signaling pathway, illuminating a potential therapeutic strategy for AD.
Hospital load and increased COVID-19 related mortality in Israel
Authors: Rossman Hagai , Meir Tomer , Somer Jonathan , Shilo Smadar , Gutman Rom , Ben Arie Asaf , Segal Eran , Shalit Uri , Gorfine Malka
Published: March 2021

The spread of Coronavirus disease 19 (COVID-19) has led to many healthcare systems being overwhelmed by the rapid emergence of new cases. Here, we study the ramifications of hospital load due to COVID-19 morbidity on in-hospital mortality of patients with COVID-19 by analyzing records of all 22,636 COVID-19 patients hospitalized in Israel from mid-July 2020 to mid-January 2021. We show that even under moderately heavy patient load (>500 countrywide hospitalized severely-ill patients; the Israeli Ministry of Health defined 800 severely-ill patients as the maximum capacity allowing adequate treatment), in-hospital mortality rate of patients with COVID-19 significantly increased compared to periods of lower patient load (250–500 severely-ill patients): 14-day mortality rates were 22.1% (Standard Error 3.1%) higher (mid-September to mid-October) and 27.2% (Standard Error 3.3%) higher (mid-December to mid-January). We further show this higher mortality rate cannot be attributed to changes in the patient population during periods of heavier load.
A noninvasive fluorescence imaging-based platform measures 3D anisotropic extracellular diffusion
Authors: Chen Peng , Chen Xun , Hepfer R. Glenn , Damon Brooke J. , Shi Changcheng , Yao Jenny J. , Coombs Matthew C. , Kern Michael J. , Ye Tong , Yao Hai
Published: March 2021

Diffusion is a major molecular transport mechanism in biological systems. Quantifying direction-dependent (i.e., anisotropic) diffusion is vitally important to depicting how the three-dimensional (3D) tissue structure and composition affect the biochemical environment, and thus define tissue functions. However, a tool for noninvasively measuring the 3D anisotropic extracellular diffusion of biorelevant molecules is not yet available. Here, we present light-sheet imaging-based Fourier transform fluorescence recovery after photobleaching (LiFT-FRAP), which noninvasively determines 3D diffusion tensors of various biomolecules with diffusivities up to 51 µm2 s−1, reaching the physiological diffusivity range in most biological systems. Using cornea as an example, LiFT-FRAP reveals fundamental limitations of current invasive two-dimensional diffusion measurements, which have drawn controversial conclusions on extracellular diffusion in healthy and clinically treated tissues. Moreover, LiFT-FRAP demonstrates that tissue structural or compositional changes caused by diseases or scaffold fabrication yield direction-dependent diffusion changes. These results demonstrate LiFT-FRAP as a powerful platform technology for studying disease mechanisms, advancing clinical outcomes, and improving tissue engineering.
Host-derived lipids orchestrate pulmonary γδ T cell response to provide early protection against influenza virus infection
Authors: Wang Xiaohui , Lin Xiang , Zheng Zihan , Lu Bingtai , Wang Jun , Tan Andy Hee-Meng , Zhao Meng , Loh Jia Tong , Ng Sze Wai , Chen Qian , Xiao Fan , Huang Enyu , Ko King-Hung , Huang Zhong , Li Jingyi , Kok Kin-Hang , Lu Gen , Liu Xiaohui , Lam Kong-Peng , Liu Wanli , Zhang Yuxia , Yuen Kwok-Yung , Mak Tak Wah , Lu Liwei
Published: March 2021

Innate immunity is important for host defense by eliciting rapid anti-viral responses and bridging adaptive immunity. Here, we show that endogenous lipids released from virus-infected host cells activate lung γδ T cells to produce interleukin 17 A (IL-17A) for early protection against H1N1 influenza infection. During infection, the lung γδ T cell pool is constantly supplemented by thymic output, with recent emigrants infiltrating into the lung parenchyma and airway to acquire tissue-resident feature. Single-cell studies identify IL-17A-producing γδ T (Tγδ17) cells with a phenotype of TCRγδhiCD3hiAQP3hiCXCR6hiin both infected mice and patients with pneumonia. Mechanistically, host cell-released lipids during viral infection are presented by lung infiltrating CD1d+B-1a cells to activate IL-17A production in γδ T cells via γδTCR-mediated IRF4-dependent transcription. Reduced IL-17A production in γδ T cells is detected in mice either lacking B-1a cells or with ablated CD1d in B cells. Our findings identify a local host-immune crosstalk and define important cellular and molecular mediators for early innate defense against lung viral infection.
Learned adaptive multiphoton illumination microscopy for large-scale immune response imaging
Authors: Pinkard Henry , Baghdassarian Hratch , Mujal Adriana , Roberts Ed , Hu Kenneth H. , Friedman Daniel Haim , Malenica Ivana , Shagam Taylor , Fries Adam , Corbin Kaitlin , Krummel Matthew F. , Waller Laura
Published: March 2021

Multiphoton microscopy is a powerful technique for deep in vivo imaging in scattering samples. However, it requires precise, sample-dependent increases in excitation power with depth in order to generate contrast in scattering tissue, while minimizing photobleaching and phototoxicity. We show here how adaptive imaging can optimize illumination power at each point in a 3D volume as a function of the sample’s shape, without the need for specialized fluorescent labeling. Our method relies on training a physics-based machine learning model using cells with identical fluorescent labels imaged in situ. We use this technique for in vivo imaging of immune responses in mouse lymph nodes following vaccination. We achieve visualization of physiologically realistic numbers of antigen-specific T cells (~2 orders of magnitude lower than previous studies), and demonstrate changes in the global organization and motility of dendritic cell networks during the early stages of the immune response. We provide a step-by-step tutorial for implementing this technique using exclusively open-source hardware and software.
DNA interstrand cross-links induced by the major oxidative adenine lesion 7,8-dihydro-8-oxoadenine
Authors: Rozelle Aaron L. , Cheun Young , Vilas Caroline K. , Koag Myong-Chul , Lee Seongmin
Published: March 2021

Oxidative damage to DNA generates 7,8-dihydro-8-oxoguanine (oxoG) and 7,8-dihydro-8-oxoadenine (oxoA) as two major lesions. Despite the comparable prevalence of these lesions, the biological effects of oxoA remain poorly characterized. Here we report the discovery of a class of DNA interstrand cross-links (ICLs) involving oxidized nucleobases. Under oxidative conditions, oxoA, but not oxoG, readily reacts with an opposite base to produce ICLs, highlighting a latent alkylating nature of oxoA. Reactive halogen species, one-electron oxidants, and the myeloperoxidase/H2O2/Cl− system induce oxoA ICLs, suggesting that oxoA-mediated cross-links may arise endogenously. Nucleobase analog studies suggest C2-oxoA is covalently linked to N2-guanine and N3-adenine for the oxoA-G and oxoA-A ICLs, respectively. The oxoA ICLs presumably form via the oxidative activation of oxoA followed by the nucleophilic attack by an opposite base. Our findings provide insights into oxoA-mediated mutagenesis and contribute towards investigations of oxidative stress-induced ICLs and oxoA-based latent alkylating agents.
Long-term and large-scale multispecies dataset tracking population changes of common European breeding birds
Authors: Brlík Vojtěch , Šilarová Eva , Škorpilová Jana , Alonso Hany , Anton Marc , Aunins Ainars , Benkö Zoltán , Biver Gilles , Busch Malte , Chodkiewicz Tomasz , Chylarecki Przemysław , Coombes Dick , de Carli Elisabetta , del Moral Juan C. , Derouaux Antoine , Escandell Virginia , Eskildsen Daniel P. , Fontaine Benoît , Foppen Ruud P. B. , Gamero Anna , Gregory Richard D. , Harris Sarah , Herrando Sergi , Hristov Iordan , Husby Magne , Ieronymidou Christina , Jiquet Frédéric , Kålås John A. , Kamp Johannes , Kmecl Primož , Kurlavičius Petras , Lehikoinen Aleksi , Lewis Lesley , Lindström Åke , Manolopoulos Aris , Martí David , Massimino Dario , Moshøj Charlotte , Nellis Renno , Noble David , Paquet Alain , Paquet Jean-Yves , Portolou Danae , Ramírez Iván , Redel Cindy , Reif Jiří , Ridzoň Jozef , Schmid Hans , Seaman Benjamin , Silva Laura , Soldaat Leo , Spasov Svetoslav , Staneva Anna , Szép Tibor , Florenzano Guido Tellini , Teufelbauer Norbert , Trautmann Sven , van der Meij Tom , van Strien Arco , van Turnhout Chris , Vermeersch Glenn , Vermouzek Zdeněk , Vikstrøm Thomas , Voříšek Petr , Weiserbs Anne , Klvaňová Alena
Published: March 2021

Around fifteen thousand fieldworkers annually count breeding birds using standardized protocols in 28 European countries. The observations are collected by using country-specific and standardized protocols, validated, summarized and finally used for the production of continent-wide annual and long-term indices of population size changes of 170 species. Here, we present the database and provide a detailed summary of the methodology used for fieldwork and calculation of the relative population size change estimates. We also provide a brief overview of how the data are used in research, conservation and policy. We believe this unique database, based on decades of bird monitoring alongside the comprehensive summary of its methodology, will facilitate and encourage further use of the Pan-European Common Bird Monitoring Scheme results.
Discovering latent node Information by graph attention network
Authors: Gu Weiwei , Gao Fei , Lou Xiaodan , Zhang Jiang
Published: March 2021

In this paper, we propose graph attention based network representation (GANR) which utilizes the graph attention architecture and takes graph structure as the supervised learning information. Compared with node classification based representations, GANR can be used to learn representation for any given graph. GANR is not only capable of learning high quality node representations that achieve a competitive performance on link prediction, network visualization and node classification but it can also extract meaningful attention weights that can be applied in node centrality measuring task. GANR can identify the leading venture capital investors, discover highly cited papers and find the most influential nodes in Susceptible Infected Recovered Model. We conclude that link structures in graphs are not limited on predicting linkage itself, it is capable of revealing latent node information in an unsupervised way once a appropriate learning algorithm, like GANR, is provided.
Compound heterozygous mutations in TGFBI cause a severe phenotype of granular corneal dystrophy type 2
Authors: Jun Ikhyun , Ji Yong Woo , Choi Seung-il , Lee Bo Ram , Min Ji Sang , Kim Eung Kweon
Published: March 2021

We investigated the clinical and genetic features of patients with severe phenotype of granular corneal dystrophy type 2 (GCD2) associated with compound heterozygosity in the transforming growth factor-β-induced (TGFBI) gene. Patients with severe GCD2 underwent ophthalmic examination (best-corrected visual acuity test, intraocular pressure measurement, slit-lamp examination, and slit-lamp photograph analysis) and direct Sanger sequencing of whole-TGFBI. The patient’s family was tested to determine the pedigrees. Five novel mutations (p.(His174Asp), p.(Ile247Asn), p.(Tyr88Cys), p.(Arg257Pro), and p.(Tyr468*)) and two known mutations (p.(Asn544Ser) and p.(Arg179*)) in TGFBI were identified, along with p.(Arg124His), in the patients. Trans-phase of TGFBI second mutations was confirmed by pedigree analysis. Multiple, extensive discoid granular, and increased linear deposits were observed in the probands carrying p.(Arg124His) and other nonsense mutations. Some patients who had undergone phototherapeutic keratectomy experienced rapid recurrence (p.(Ile247Asn) and p.(Asn544Ser)); however, the cornea was well-maintained in a patient who underwent deep anterior lamellar keratoplasty (p.(Ile247Asn)). Thus, compound heterozygosity of TGFBI is associated with the phenotypic variability of TGFBI corneal dystrophies, suggesting that identifying TGFBI second mutations may be vital in patients with extraordinarily severe phenotypes. Our findings indicate the necessity for a more precise observation of genotype–phenotype correlation and additional care when treating TGFBI corneal dystrophies.
Field size effects on DNA damage and proliferation in normal human cell populations irradiated with X-ray microbeams
Authors: Ojima Mitsuaki , Ito Atsushi , Usami Noriko , Ohara Maki , Suzuki Keiji , Kai Michiaki
Published: March 2021

To clarify the health risks of internal radiation exposure, it is important to investigate the radiological effects of local exposure at cell levels from radioactive materials taken up by organs. Focusing on the response of cell populations post-irradiation, X-ray microbeams are very effective at reproducing the effects of local exposure within an internal exposure in vitro. The present study aims to clarify the effects of local exposure by investigating the response of normal human cell (MRC-5) populations irradiated with X-ray microbeams of different beam sizes to DNA damage. The populations of MRC-5 were locally irradiated with X-ray microbeams of 1 Gy at 0.02–1.89 mm2 field sizes, and analyzed whether the number of 53BP1 foci as DSB (DNA double strand break) per cell changed with the field size. We found that even at the same dose, the number of DSB per cell increased depending on the X-irradiated field size on the cell population. This result indicated that DNA damage repair of X-irradiated cells might be enhanced in small size fields surrounded by non-irradiated cells. This study suggests that X-irradiated cells received some signal (a rescue signal) from surrounding non-irradiated cells may be involved in the response of cell populations post-irradiation.
Predicting the membrane permeability of organic fluorescent probes by the deep neural network based lipophilicity descriptor DeepFl-LogP
Authors: Soliman Kareem , Grimm Florian , Wurm Christian A. , Egner Alexander
Published: March 2021

Light microscopy has become an indispensable tool for the life sciences, as it enables the rapid acquisition of three-dimensional images from the interior of living cells/tissues. Over the last decades, super-resolution light microscopy techniques have been developed, which allow a resolution up to an order of magnitude higher than that of conventional light microscopy. Those techniques require labelling of cellular structures with fluorescent probes exhibiting specific properties, which are supplied from outside and therefore have to surpass cell membranes. Currently, major efforts are undertaken to develop probes which can surpass cell membranes and exhibit the photophysical properties required for super-resolution imaging. However, the process of probe development is still based on a tedious and time consuming manual screening. An accurate computer based model that enables the prediction of the cell permeability based on their chemical structure would therefore be an invaluable asset for the development of fluorescent probes. Unfortunately, current models, which are based on multiple molecular descriptors, are not well suited for this task as they require high effort in the usage and exhibit moderate accuracy in their prediction. Here, we present a novel fragment based lipophilicity descriptor DeepFL-LogP, which was developed on the basis of a deep neural network. DeepFL-LogP exhibits excellent correlation with the experimental partition coefficient reference data (R2 = 0.892 and MSE = 0.359) of drug-like substances. Further a simple threshold permeability model on the basis of this descriptor allows to categorize the permeability of fluorescent probes with 96% accuracy. This novel descriptor is expected to largely simplify and speed up the development process for novel cell permeable fluorophores.
Dicer increases the indication for trastuzumab treatment in gastric cancer patients via overexpression of human epidermal growth factor receptor 2
Authors: Wu Jianhua , Zhao Qun , Zhao Yue , Zhang Xiaoyun , Tian Yuan , Guo Zhanjun
Published: March 2021

The low proportion of gastric cancer (GC) patients with high HER2 expression limits the clinical application of trastuzumab, a humanized epidermal growth factor receptor 2 (HER2) antibody targeting for GC treatment. We found that Dicer was positively correlated with HER2 expression in GC tissue by immunostaining as well as induce HER2 overexpression without increasing invasiveness of GC cell. In addition, both the growth of GC referring to cell proliferation, invasion, migration and apoptosis was inhibited by Dicer overexpression. Moreover, the HER2 overexpression induced by Dicer provided more effective and additive target for trastuzumab to amplify the inhibition effect for GC cells in vitro and in vivo. Furthermore, as assessed in a subsequent experiment, calcitriol induced HER2 overexpression and amplified the inhibition effect of trastuzumab in GC cells referring to proliferation. Our finding demonstrated the calcitriol might increase indication of trastuzumab by inducing HER2 overexpression in GC patients. Dicer would be a potential target that extend the clinical indications of HER2 antibody in patients with low or negative HER2, who were not fit for HER2 antibody treatment before.
Free-water diffusion tensor imaging improves the accuracy and sensitivity of white matter analysis in Alzheimer’s disease
Authors: Bergamino Maurizio , Walsh Ryan R. , Stokes Ashley M.
Published: March 2021

Magnetic resonance imaging (MRI) based diffusion tensor imaging (DTI) can assess white matter (WM) integrity through several metrics, such as fractional anisotropy (FA), axial/radial diffusivities (AxD/RD), and mode of anisotropy (MA). Standard DTI is susceptible to the effects of extracellular free water (FW), which can be removed using an advanced free-water DTI (FW-DTI) model. The purpose of this study was to compare standard and FW-DTI metrics in the context of Alzheimer’s disease (AD). Data were obtained from the Open Access Series of Imaging Studies (OASIS-3) database and included both healthy controls (HC) and mild-to-moderate AD. With both standard and FW-DTI, decreased FA was found in AD, mainly in the corpus callosum and fornix, consistent with neurodegenerative mechanisms. Widespread higher AxD and RD were observed with standard DTI; however, the FW index, indicative of AD-associated neurodegeneration, was significantly elevated in these regions in AD, highlighting the potential impact of free water contributions on standard DTI in neurodegenerative pathologies. Using FW-DTI, improved consistency was observed in FA, AxD, and RD, and the complementary FW index was higher in the AD group as expected. With both standard and FW-DTI, higher values of MA coupled with higher values of FA in AD were found in the anterior thalamic radiation and cortico-spinal tract, most likely arising from a loss of crossing fibers. In conclusion, FW-DTI better reflects the underlying pathology of AD and improves the accuracy of DTI metrics related to WM integrity in Alzheimer’s disease.
Changes in respiratory mechanics of artificial pneumothorax two-lung ventilation in video-assisted thoracoscopic esophagectomy in prone position
Authors: Tanigawa Yoshinori , Nakamura Kimihide , Yamashita Tomoko , Nakagawachi Akira , Sakaguchi Yoshiro
Published: March 2021

We aimed to clarify the changes in respiratory mechanics and factors associated with them in artificial pneumothorax two-lung ventilation in video-assisted thoracoscopic esophagectomy in the prone position (PP-VATS-E) for esophageal cancer. Data of patients with esophageal cancer, who underwent PP-VATs-E were retrospectively analyzed. Our primary outcome was the change in the respiratory mechanics after intubation (T1), in the prone position (T2), after initiation of the artificial pneumothorax two-lung ventilation (T3), at 1 and 2 h (T4 and T5), in the supine position (T6), and after laparoscopy (T7). The secondary outcome was identifying factors affecting the change in dynamic lung compliance (Cdyn). Sixty-seven patients were included. Cdyn values were significantly lower at T3, T4, and T5 than at T1 (p < 0.001). End-expiratory flow was significantly higher at T4 and T5 than at T1 (p < 0.05). Body mass index and preoperative FEV1.0% were found to significantly influence Cdyn reduction during artificial pneumothorax and two-lung ventilation (OR [95% CI]: 1.29 [1.03–2.24] and 0.20 (0.05–0.44); p = 0.010 and p = 0.034, respectively]. Changes in driving pressure were nonsignificant, and hypoxemia requiring treatment was not noted. This study suggests that in PP-VATs-E, artificial pneumothorax two-lung ventilation is safer for the management of anesthesia than conventional one-lung ventilation (UMIN Registry: 000042174).
Publisher Correction: A novel therapeutic antibody screening method using bacterial high-content imaging reveals functional antibody binding phenotypes of Escherichia coli ST131
Authors: Maes Mailis , Dyson Zoe A. , Smith Sarah E. , Goulding David A. , Ludden Catherine , Baker Stephen , Kellam Paul , Reece Stephen T. , Dougan Gordon , Bartholdson Scott Josefin
Published: March 2021

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Optimization ofJiuzaoprotein hydrolysis conditions and antioxidant activityin vivoofJiuzaotetrapeptide Asp-Arg-Glu-Leu by elevating the Nrf2/Keap1-p38/PI3K-MafK signaling pathway
Authors: Jiang Yunsong , Wang Rui , Yin Zhongtian , Sun Jinyuan , Wang Bowen , Zhao Dongrui , Zeng Xin-an , Li Hehe , Huang Mingquan , Sun Baoguo
Published: March 2021

Tetrapeptide DREL fromJiuzaoexhibits antioxidant and anti-inflammatory activities through activating the Nfr2/Keap1-p38/PI3K-MafK signaling pathway and downstream antioxidant enzymes.
Stimulatory effects of (−)-epicatechin and its enantiomer (+)-epicatechin on mouse frontal cortex neurogenesis markers and short-term memory: proof of concept
Authors: Navarrete-Yañez Viridiana , Garate-Carrillo Alejandra , Ayala Marcos , Rodriguez-Castañeda Antonio , Mendoza-Lorenzo Patricia , Ceballos Guillermo , Ordoñez-Razo Rosa , Dugar Sundeep , Schreiner George , Villarreal Francisco , Ramirez-Sanchez Israel
Published: March 2021

(−)-Epicatechin and (+)-epicatechin, upregulate neurogenesis markers likely through stimulation of capillary formation and nitric oxide triggering, improvements in memory.
Protein–saliva interactions: a systematic review
Authors: Brown Frances N. , Mackie Alan R. , He Qi , Branch Alison , Sarkar Anwesha
Published: March 2021

Demographics of studies investigating protein–saliva interaction. Numbers reflect the number of studies using each method, protein type or system.
Potential beneficial effects of kefir and its postbiotic, kefiran, on child food allergy
Authors: Barros Susy Érika de Lima , Rocha Caique dos Santos , de Moura Mayara Storel Beserra , Barcelos Mariana Pegrucci , da Silva Carlos Henrique Tomich de Paula , Hage-Melim Lorane Izabel da Silva
Published: March 2021

Food allergies are known as the public health problem, affecting people of all age groups, but more commonly in babies and children, with consequences for nutritional status and quality of life.
Lycopene attenuates di(2-ethylhexyl) phthalate-induced mitophagy in spleen by regulating the sirtuin3-mediated pathway
Authors: Dai Xue-Yan , Zhao Yi , Ge Jing , Zhu Shi-Yong , Li Mu-Zi , Talukder Milton , Li Jin-Long
Published: March 2021

In this study, it was shown that lycopene supplementation can effectively ameliorate the di(2-ethylhexyl) phthalate-induced mitochondrial homeostasis balance and mitophagy via activation of the SIRT3 and Parkin/PINK pathways.
Nanoparticle-sensitized photoporation enables inflammasome activation studies in targeted single cells
Authors: Harizaj Aranit , Van Hauwermeiren Filip , Stremersch Stephan , De Rycke Riet , De Keersmaecker Herlinde , Brans Toon , Fraire Juan C. , Grauwen Karolien , De Smedt Stefaan C. , Lentacker Ine , Lamkanfi Mohamed , Braeckmans Kevin
Published: March 2021

Laser-induced nanoparticle-sensitized photoporation of hard-to-transfect primary macrophages for the ex vivo delivery of inflammasome inducing toxins.
Nanostructured metal nitrides for photocatalysts
Authors: Rao Tingke , Cai Wen , Zhang Han , Liao Wugang
Published: March 2021

The morphology, size, defects and nanostructured construction of metal nitrides (MNs) are demonstrated to be critical factors in their catalytic efficiency for water spitting and CO2 reduction, emphasizing the importance of their synthetic methods.
Enhanced performance of a surface plasmon resonance-based immunosensor for the detection of glycocholic acid
Authors: He Qiyi , Fang Yanxiong , Yang Huiyi , Shen Ding , Chen Yingshan , Zhong Yingying , Li Xiangguang , Eremin Sergei A. , Cui Xiping , Zhao Suqing
Published: March 2021

The concentration of glycocholic acid (GCA) in urine and blood is an important biomarker for liver cancer.
Water-stable lanthanide–organic macrocycles from a 1,2,4-triazole-based chelate for enantiomeric excess detection and pesticide sensing
Authors: Cheng Kai , Bai Qi-Xia , Hu Shao-Jun , Guo Xiao-Qing , Zhou Li-Peng , Xie Ting-Zheng , Sun Qing-Fu
Published: March 2021

Water-stable anionic Ln2L2-type macrocycles have been constructed from a 1,2,4-triazole-based ligand, of which the luminescent Eu2L2 macrocycle can be used for ee detection toward pybox-type chiral ligands and selective sensing of OMA in water.
A comparative study of the effects of phosphatidylserine rich in DHA and EPA on Aβ-induced Alzheimer's disease using cell models
Authors: Xu Zhen-Jing , Li Qian , Ding Lin , Shi Hao-Hao , Xue Chang-Hu , Mao Xiang-Zhao , Wang Yu-Ming , Zhang Tian-Tian
Published: March 2021

The possible underlying mechanisms of EPA-PS and DHA-PS for the generation and clearance of Aβ and alleviation of Aβ-induced neurotoxicity in cellular models.
Magneto-fluorescent nanocomposites: experimental and theoretical linkage for the optimization of magnetic hyperthermia
Authors: Vamvakidis Kosmas , Maniotis Nikolaos , Dendrinou-Samara Catherine
Published: March 2021

Magneto-fluorescent nanocomposites of Zn doped ferrites nanoparticles with Pt complexes for magnetic hyperthermia and fluorescent imaging.
NIR-triggered biodegradable MOF-coated upconversion nanoparticles for synergetic chemodynamic/photodynamic therapy with enhanced efficacy
Authors: Zou Man , Zhao Yajie , Ding Binbin , Jiang Fan , Chen Yeqing , Ma Ping'an , Lin Jun
Published: March 2021

The generation of reactive oxygen species (ROS) is often limited by the overexpression of glutathione (GSH) in the tumor microenvironment (TME) and the penetration depth of visible light.
Effects of an additive (hydroxyapatite–bentonite–biochar) on Cd and Pb stabilization and microbial community composition in contaminated vegetable soil
Authors: Zhang Di , Li Ting , Ding Aifang , Wu Xiaoxia
Published: March 2021

A two-year pot experiment was conducted with an amendment of hydroxyapatite, bentonite and biochar combinations (HTB) to study the influence of HTB on soil physicochemical properties, soil Cd and Pb availability and microbial community composition.
Well-dispersed Pt/RuO2-decorated mesoporous N-doped carbon as a hybrid electrocatalyst for Li–O2 batteries
Authors: Jo Hyun-Gi , Kim Kue-Ho , Ahn Hyo-Jin
Published: March 2021

The excellent performance of the Pt/RuO2@ACT electrocatalyst is promising for accelerating the commercialization of Li–O2 batteries.
Transmembrane anion transport promoted by thioamides
Authors: Pomorski Robert , García-Valverde María , Quesada Roberto , Chmielewski Michał J.
Published: March 2021

Highly active transmembrane anion carriers based on the 1,8-dithioamidocarbazole scaffold are presented, demonstrating the superior performance of thioamides as compared with their parent amides.
Broadening the absorption bandwidth by novel series–parallel cross convex–concave structures
Authors: Mei Hui , Yang Dou , Yao Li , Yang Wenqiang , Zhao Xing , Yao Yongtao , Cheng Laifei , Zhang Litong , Dassios Konstantinos G.
Published: March 2021

Novel series–parallel cross convex–concave structures fabricated by DLP 3D printing respond positively to electromagnetic waves.
Beginners guide to circular dichroism
Authors: Rodger Alison , Marshall Doug
Published: March 2021

Circular dichroism (CD) is used to give information about the chirality or handedness of molecular systems. It is particularly widely applied to determine the secondary structure of proteins such as biopharmaceutical products.
Spatial Release From Masking in Pediatric Cochlear Implant Recipients With Single-Sided Deafness
Authors: Park Lisa R. , Dillon Margaret T. , Buss Emily , O'Connell Brendan P. , Brown Kevin D.
Published: March 2021

Purpose

Children with single-sided deafness (SSD) experience difficulty understanding speech in multisource listening situations. Case reports and retrospective studies have indicated that a cochlear implant (CI) may improve masked speech recognition in children with SSD. This prospective study was conducted to determine whether providing a CI to children with SSD supports spatial release from masking (SRM), an improvement in speech recognition associated with separating the target and masker sources.

Method

Twenty children with at least a moderate-to-profound hearing loss in one ear and normal hearing in the contralateral ear underwent cochlear implantation. The average age of implantation was 5.5 years (range: 3.5–12.7). After 12 months of CI use, subjects completed a sentence recognition task in multitalker masker with and without the CI. The target was presented from the front, and the masker was either colocated with the target (0°) or from the side (+90° or −90°). A two-way repeated-measures analysis of variance was completed to investigate SRM with and without the CI.

Results

Pediatric CI recipients experienced significant SRM when the masker was directed to the normal-hearing ear or to the affected ear.

Conclusions

The results indicate that cochlear implantation in children with SSD supports binaural skills required for speech recognition in noise. These results are consistent with improved functional communication in multisource environments, like classrooms.
The Effect of Parkinson's Disease on Otoacoustic Emissions and Efferent Suppression of Transient Evoked Otoacoustic Emissions
Authors: De Groote Evelien , Bockstael Annelies , Botteldooren Dick , Santens Patrick , De Letter Miet
Published: March 2021

Purpose

Several studies have demonstrated increased auditory thresholds in patients with Parkinson's disease (PD) based on subjective tonal audiometry. However, the pathophysiological mechanisms underlying auditory dysfunction in PD remain elusive. The primary aim of this study was to investigate cochlear and olivocochlear function in PD using objective measurements and to assess the effect of dopaminergic medication on auditory function.

Method

Eighteen patients with PD and 18 gender- and age-matched healthy controls (HCs) were included. Patients with PD participated in medication on and off conditions. Linear mixed models were used to determine the effect of PD on tonal audiometry, transient evoked and distortion product otoacoustic emissions (OAEs), and efferent suppression (ES).

Results

Tonal audiometry revealed normal auditory thresholds in patients with PD for their age across all frequencies. OAE signal amplitudes demonstrated a significant interaction effect between group (PD vs. HC) and frequency, indicating decreased OAEs at low frequencies and increased OAEs at high frequencies in patients with PD. No significant differences were found between patients with PD and HCs regarding ES. In addition, no significant effect of medication status was found on auditory measurements in patients with PD.

Conclusions

Altered OAEs support the hypothesis of cochlear alterations in PD. No evidence was found for the involvement of the medial olivocochlear system. Altogether, OAEs may provide an objective early indicator of auditory alterations in PD and should complement subjective tonal audiometry when assessing and monitoring auditory function in PD.
Second‐order SMO‐based sensorless control of IM drive: experimental investigations of observer sensitivity and system reconfiguration in postfault operation mode
Authors: Maamouri Rebah , Trabelsi Mohamed , Boussak Mohamed , M'Sahli Faouzi
Published: March 2021

In normal operation mode, sensorless speed‐controlled motor drives should be more reliable, less expensive and less bulky than their counterparts with a speed sensor. The sensorless drive structure allows avoiding the electromagnetic and vibratory sensitivity of the mechanical sensor, the additional connecting circuits, additional space for the sensor, its price and maintenance requirements. However, in postfault operation mode, the robustness of speed sensorless control strategies has been poorly addressed in the study. Accordingly, this study deals with an experimental study of the robustness and the availability of speed‐controlled induction motor (IM) drives without speed sensor in the presence of inverter open‐switches faults. For that purpose, a super twisting algorithm‐based observer for motor speed estimation is proposed for experimental investigation. Experimental results are performed upon 3‐kW IM drive by using dSPACE digital signal processing controller board. Experimental investigations evaluate the performances of the method used for the control without speed sensor in prefault, postfault and regeneration operation modes.
Application of simplified convolutional neural networks for initial stator winding fault detection of the PMSM drive using different raw signal data
Authors: Skowron Maciej , Orlowska‐Kowalska Teresa , Kowalski Czeslaw T.
Published: March 2021

Permanent magnet synchronous motors (PMSM) have become one of the most substantial components of modern industrial drives. These motors, like all the others, can unfortunately undergo various failures, causing production line downtime and resulting losses. Accordingly, it is necessary to develop fault diagnostic techniques which detect the damages at the earliest possible stage. This study presents a method of detecting incipient faults of the PMSM stator windings using direct signal analysis and a convolutional neural network (CNN). During the tests, the structures of CNN were optimised to constitute a balance between the high efficiency of fault detection and a small number of network parameters. The effectiveness of the CNNs with inputs constituted by different electrical signals measured in the drive system is compared. Three raw data signals are tested as CNN inputs, namely: stator phase currents, phase‐to‐phase voltages and axial flux, without data preprocessing. The article aims to show the possibility of detecting the incipient interturn short circuits in the PMSM stator winding based on the information obtained directly from the measured signals as well as to present the influence of the drive operating conditions and the type of measurement signals used on the structure and performance of the developed CNNs.