bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterizing the roles of bots on Twitter during the COVID-19 infodemic
Authors: Xu Wentao , Sasahara Kazutoshi
Published: August 2021

An infodemic is an emerging phenomenon caused by an overabundance of information online. This proliferation of information makes it difficult for the public to distinguish trustworthy news and credible information from untrustworthy sites and non-credible sources. The perils of an infodemic debuted with the outbreak of the COVID-19 pandemic and bots (i.e., automated accounts controlled by a set of algorithms) that are suspected of spreading the infodemic. Although previous research has revealed that bots played a central role in spreading misinformation during major political events, how bots behavior during the infodemic is unclear. In this paper, we examined the roles of bots in the case of the COVID-19 infodemic and the diffusion of non-credible information such as “5G” and “Bill Gates” conspiracy theories and content related to “Trump” and “WHO” by analyzing retweet networks and retweeted items. We show the segregated topology of their retweet networks, which indicates that right-wing self-media accounts and conspiracy theorists may lead to this opinion cleavage, while malicious bots might favor amplification of the diffusion of non-credible information. Although the basic influence of information diffusion could be larger in human users than bots, the effects of bots are non-negligible under an infodemic situation.
Saving Nature Under Socialism
Authors: Ault Julia E.
Published: August 2021

When East Germany collapsed in 1989–1990, outside observers were shocked to learn the extent of environmental devastation that existed there. The communist dictatorship, however, had sought to confront environmental issues since at least the 1960s. Through an analysis of official and oppositional sources, Saving Nature Under Socialism complicates attitudes toward the environment in East Germany by tracing both domestic and transnational engagement with nature and pollution. The communist dictatorship limited opportunities for protest, so officials and activists looked abroad to countries such as Poland and West Germany for inspiration and support. Julia Ault outlines the evolution of environmental policy and protest in East Germany and shows how East Germans responded to local degradation as well as to an international moment of environmental reckoning in the 1970s and 1980s. The example of East Germany thus challenges and broadens our understanding of the 'greening' of post-war Europe, and illuminates a larger, central European understanding of connection across the Iron Curtain.
The Dependence of Tropical Modes of Variability on Zonal Asymmetry
Authors: Wu Xiaoning , Reed Kevin A. , Wolfe Christopher L. P. , Marques Gustavo M. , Bachman Scott D. , Bryan Frank O.
Published: August 2021

Tropical modes of variability, including the Madden‐Julian Oscillation (MJO) and the El Niño‐Southern Oscillation (ENSO), are challenging to represent in climate models. Previous studies suggest their fundamental dependence on zonal asymmetry, but such dependence is rarely addressed with fully coupled ocean dynamics. This study fills the gap by using fully coupled, idealized Community Earth System Model (CESM) and comparing two nominally ocean‐covered configurations with and without a meridional boundary. For the MJO‐like intraseasonal mode, its separation from equatorial Kelvin waves and the eastward propagation of its convective and dynamic signals depend on the zonal gradient of the mean state. For the ENSO‐like interannual mode, in the absence of the ocean's meridional boundary, a circum‐equatorial dominant mode emerges with distinct ocean dynamics. The interpretation of the dependence of these modes on zonal asymmetry is relevant to their representation in realistic climate models.
Evolution of the Horizontal Winds in Jupiter's Great Red Spot From One Jovian Year of HST/WFC3 Maps
Authors: Wong Michael H. , Marcus Philip S. , Simon Amy A. , de Pater Imke , Tollefson Joshua W. , Asay‐Davis Xylar
Published: August 2021

We measured the horizontal winds in Jupiter's Great Red Spot (GRS) using data from the WFC3/UVIS instrument on board the Hubble Space Telescope (HST). The data cover 11 epochs from 2009 to 2020. Long‐term monotonic trends in size and shape previously noted from the visible cloud appearance are paralleled by changes in the high‐speed ring around the vortex. The circularization of the GRS cannot be explained by changes in the horizontal wind shear of the surrounding environment. The velocity fields suggest no long‐term trend in the static stability inside or outside the vortex. Instead, the changes are accompanied by a 4%–8% increase in the mean wind speeds of the high‐speed ring from 2009 to 2020. Changes in the wind field coincided with the South Equatorial Belt Outbreak storms of 2016–2017, but not with 2019 "flaking" events involving detachment of red material from the main oval.
Influence of Climate‐Forcing Frequency on Hillslope Response
Authors: Godard V. , Tucker G. E.
Published: August 2021

Assessing rivers' and hillslopes' sensitivity to external forcing is paramount to understand landscape evolution, in particular as a response to Quaternary climate changes. River networks are usually considered to be the main conveyors of environmental signals, such as changes in precipitation, temperature, or baselevel. Yet because hillslopes provide the source of sediment for river networks, their response to environmental change also modulates landscape dynamics. In order to characterize such behavior, we analyze the response times of a transport‐limited hillslope. We use simple numerical models of denudation to study hillslope responses to oscillatory forcing and understand their filtering effects on environmental signals. Modifications in the frequency of climate oscillation, such as the change that occurred at the Mid‐Pleistocene Transition, can significantly modulate hillslope sediment‐flux response. We infer a wide range of hillslope responses, ranging from negligible change over the full range of climate‐forcing frequencies, to a significant filtering of long‐period signals.
A Combined Rock Magnetic and Meteorological Investigation of the Precipitation Boundary Across the Tibetan Plateau
Authors: Ning Wen‐Xiao , Zan Jin‐Bo , Yang Sheng‐Li , Fang Xiao‐Min , Shen Miao‐Miao , Kang Jian , Luo Yuan‐Long , Wang Shu‐Wen
Published: August 2021

Characterizing the spatial distribution of precipitation across the Tibetan Plateau (TP) is important for understanding how the topography and atmospheric circulation influence the climatic patterns of the region. We collected 143 surface soil samples from the central and southeastern TP (SETP) for rock magnetic characterization of the spatial distribution of the pedogenic intensity. Comparison with meteorological data shows that pedogenic intensity decreases significantly along the pathway of moist air across the SETP toward the interior, and that there is a positive correlation between pedogenic magnetite/maghemite content and mean annual precipitation. By contrast, the samples from the central TP show a low degree of pedogenic alteration, consistent with the limited precipitation within this area. The results indicate the possibility of using magnetic properties of surface soils to determine the precipitation distribution in areas lacking meteorological stations. These observations, combined with published soil magnetic results, help to define the climatic boundary in the TP.
First Results From the Retrieved Column O/N2 Ratio From the Ionospheric Connection Explorer (ICON): Evidence of the Impacts of Nonmigrating Tides
Authors: England Scott L. , Meier R. R. , Frey Harald U. , Mende Stephen B. , Stephan Andrew W. , Krier Christopher S. , Cullens Chihoko Y. , Wu Yen‐Jung J. , Triplett Colin C. , Sirk Martin M. , Korpela Eric J. , Harding Brian J. , Englert Christoph R. , Immel Thomas J.
Published: August 2021

In near‐Earth space, variations in thermospheric composition have important implications for thermosphere‐ionosphere coupling. The ratio of O to N2 is often measured using far‐UV airglow observations. Taking such airglow observations from space, looking below the Earth's limb allows for the total column of O and N2 in the ionosphere to be determined. While these observations have enabled many previous studies, determining the impact of nonmigrating tides on thermospheric composition has proved difficult, owing to a small contamination of the signal by recombination of ionospheric O+. New ICON observations of far‐UV are presented here, and their general characteristics are shown. Using these, along with other observations and a global circulation model, we show that during the morning hours and at latitudes away from the peak of the equatorial ionospheric anomaly, the impact of nonmigrating tides on thermospheric composition can be observed. During March–April 2020, the column O/N2 ratio was seen to vary by 3–4% of the zonal mean. By comparing the amplitude of the variation observed with that in the model, both the utility of these observations and a pathway to enable future studies is shown.
Viscoplastic Rheology of α‐Quartz Investigated by Nanoindentation
Authors: Strozewski Benjamin , Sly Michael K. , Flores Katharine M. , Skemer Philip
Published: August 2021

Quartz is an abundant mineral in Earth's crust whose mechanical behavior plays a significant role in the deformation of the continental lithosphere. However, the viscoplastic rheology of quartz is difficult to measure experimentally at low temperatures without high confining pressures due to the tendency of quartz (and other geologic materials) to fracture under these conditions. Instrumented nanoindentation experiments inhibit cracking even at ambient conditions, by imposing locally high mean stress, allowing for the measurement of the viscoplastic rheology of hard materials over a wide range of temperatures. Here we measure the indentation hardness of four synthetic quartz specimens and one natural quartz specimen with varying water contents over a temperature range of 23°C to 500°C. Yield stress, which is calculated from hardness but is model dependent, is fit to a constitutive flow law for low‐temperature plasticity to estimate the athermal Peierls stress of quartz. Below 500°C, the yield stresses presented here are lower than those obtained by extrapolating a flow law constrained by experiments at higher temperatures irrespective of the applied model. Indentation hardness and yield stress depend weakly on crystallographic orientation but show no dependence on water content.
A Link Between Plant Stress and Hydrodynamics? Indications From a Freshwater Macrophyte
Authors: Vettori D. , Niewerth S. , Aberle J. , Rice S. P.
Published: August 2021

Live plants are increasingly used in hydraulic laboratories to investigate flow‐vegetation interactions. In such experiments, they are often exposed to stressful handling and storage that can cause strong physiological responses and modifications in plant biomechanics. Little is known about the potential effect of these impacts on the performance of plants during hydraulic experiments. In this multidisciplinary study with a freshwater macrophyte (Potamogeton natans) we assess whether the duration and the conditions in which plants are stored in a laboratory prior to testing can impact plant stress, biomechanics and hydrodynamics, and quantify this impact. Plant stress was evaluated using chlorophyll fluorescence analysis (and the maximum quantum yield of photosystem II as specific indicator). Plant hydrodynamics were assessed using the drag coefficient calculated from drag force measurements at two flow scenarios. The results show that different plant handling/storage procedures can have a significant impact on plant hydrodynamics even within a short time frame, with a variation of the mean drag coefficient of approximately 30% across groups, which is comparable to the variation found across different species of freshwater macrophytes in previous studies. Plants with the highest level of stress were also characterized by the lowest drag coefficient across the groups considered, suggesting a potential link between plant stress and hydrodynamics.
Quantum superposition demonstrated higher-order topological bound states in the continuum
Authors: Wang Yao , Xie Bi-Ye , Lu Yong-Heng , Chang Yi-Jun , Wang Hong-Fei , Gao Jun , Jiao Zhi-Qiang , Feng Zhen , Xu Xiao-Yun , Mei Feng , Jia Suotang , Lu Ming-Hui , Jin Xian-Min
Published: August 2021

Higher-order topological insulators, as newly found non-trivial materials and structures, possess topological phases beyond the conventional bulk-boundary correspondence. In previous studies, in-gap boundary states such as the corner states were regarded as conclusive evidence for the emergence of higher-order topological insulators. Here, we present an experimental observation of a photonic higher-order topological insulator with corner states embedded into the bulk spectrum, denoted as the higher-order topological bound states in the continuum. Especially, we propose and experimentally demonstrate a new way to identify topological corner states by exciting them separately from the bulk states with photonic quantum superposition states. Our results extend the topological bound states in the continuum into higher-order cases, providing an unprecedented mechanism to achieve robust and localized states in a bulk spectrum. More importantly, our experiments exhibit the advantage of using the time evolution of quantum superposition states to identify topological corner modes, which may shed light on future exploration between quantum dynamics and higher-order topological photonics.
Ribosomal proteins and human diseases: molecular mechanisms and targeted therapy
Authors: Kang Jian , Brajanovski Natalie , Chan Keefe T. , Xuan Jiachen , Pearson Richard B. , Sanij Elaine
Published: August 2021

Ribosome biogenesis and protein synthesis are fundamental rate-limiting steps for cell growth and proliferation. The ribosomal proteins (RPs), comprising the structural parts of the ribosome, are essential for ribosome assembly and function. In addition to their canonical ribosomal functions, multiple RPs have extra-ribosomal functions including activation of p53-dependent or p53-independent pathways in response to stress, resulting in cell cycle arrest and apoptosis. Defects in ribosome biogenesis, translation, and the functions of individual RPs, including mutations in RPs have been linked to a diverse range of human congenital disorders termed ribosomopathies. Ribosomopathies are characterized by tissue-specific phenotypic abnormalities and higher cancer risk later in life. Recent discoveries of somatic mutations in RPs in multiple tumor types reinforce the connections between ribosomal defects and cancer. In this article, we review the most recent advances in understanding the molecular consequences of RP mutations and ribosomal defects in ribosomopathies and cancer. We particularly discuss the molecular basis of the transition from hypo- to hyper-proliferation in ribosomopathies with elevated cancer risk, a paradox termed “Dameshek’s riddle.” Furthermore, we review the current treatments for ribosomopathies and prospective therapies targeting ribosomal defects. We also highlight recent advances in ribosome stress-based cancer therapeutics. Importantly, insights into the mechanisms of resistance to therapies targeting ribosome biogenesis bring new perspectives into the molecular basis of cancer susceptibility in ribosomopathies and new clinical implications for cancer therapy.
Loss of ID3 drives papillary thyroid cancer metastasis by targeting E47-mediated epithelial to mesenchymal transition
Authors: Xu Sunwang , Mo Caiqin , Lin Junyu , Yan Yixing , Liu Xiaoyu , Wu Kunlin , Zhang Huihao , Zhu Youzhi , Chen Ling , Chen Xiangjin
Published: August 2021

Papillary thyroid cancer (PTC) is the main histological type of thyroid cancer and accounts for almost all increased cases worldwide. Patients with PTC exhibit a favorable prognosis, but the fact that PTC is often accompanied by a high prevalence of lymph node metastasis (LNM) means that the overall recurrence-free survival rate in PTC patients is relatively low. Herein, we identified that ID3 expression is subdued in PTC tissues and closely associated with LNM and a poor disease-free survival outcome in PTC patients. The main contributor to this gene repression is the hypermethylation of the CpG island at the promoter of ID3. Besides, we uncovered that a loss of ID3 promotes invasion and migration of PTC cells, while an ectopic overexpression of ID3 inhibits invasion and migration. Mechanistically, ID3 exhibits tumor suppressor functions in PTC cells by interacting with E47 to form heterodimers that prevent E47 binding to CDH1 promoter and maintaining CDH1 transcription and epithelial phenotype in PTC cells. Taken together, our study demonstrates that ID3 plays a tumor suppressor role in PTC and impedes metastasis by inhibiting E47-mediated epithelial to mesenchymal transition.
Subclass and avidity of circumsporozoite protein specific antibodies associate with protection status against malaria infection
Authors: Seaton Kelly E. , Spreng Rachel L. , Abraha Milite , Reichartz Matthew , Rojas Michelle , Feely Frederick , Huntwork Richard H. C. , Dutta Sheetij , Mudrak Sarah V. , Alam S. Munir , Gregory Scott , Jongert Erik , Coccia Margherita , Ulloa-Montoya Fernando , Wille-Reece Ulrike , Tomaras Georgia D. , Dennison S. Moses
Published: August 2021

RTS,S/AS01 is an advanced pre-erythrocytic malaria vaccine candidate with demonstrated vaccine efficacy up to 86.7% in controlled human malaria infection (CHMI) studies; however, reproducible immune correlates of protection (CoP) are elusive. To identify candidates of humoral correlates of vaccine mediated protection, we measured antibody magnitude, subclass, and avidity for Plasmodium falciparum (Pf) circumsporozoite protein (CSP) by multiplex assays in two CHMI studies with varying RTS,S/AS01B vaccine dose and timing regimens. Central repeat (NANP6) IgG1 magnitude correlated best with protection status in univariate analyses and was the most predictive for protection in a multivariate model. NANP6 IgG3 magnitude, CSP IgG1 magnitude, and total serum antibody dissociation phase area-under-the-curve for NANP6, CSP, NPNA3, and N-interface binding were also associated with protection status in the regimen adjusted univariate analysis. Identification of multiple immune response features that associate with protection status, such as antibody subclasses, fine specificity and avidity reported here may accelerate development of highly efficacious vaccines against P. falciparum.
LIVECell—A large-scale dataset for label-free live cell segmentation
Authors: Edlund Christoffer , Jackson Timothy R. , Khalid Nabeel , Bevan Nicola , Dale Timothy , Dengel Andreas , Ahmed Sheraz , Trygg Johan , Sjögren Rickard
Published: August 2021

Light microscopy combined with well-established protocols of two-dimensional cell culture facilitates high-throughput quantitative imaging to study biological phenomena. Accurate segmentation of individual cells in images enables exploration of complex biological questions, but can require sophisticated imaging processing pipelines in cases of low contrast and high object density. Deep learning-based methods are considered state-of-the-art for image segmentation but typically require vast amounts of annotated data, for which there is no suitable resource available in the field of label-free cellular imaging. Here, we present LIVECell, a large, high-quality, manually annotated and expert-validated dataset of phase-contrast images, consisting of over 1.6 million cells from a diverse set of cell morphologies and culture densities. To further demonstrate its use, we train convolutional neural network-based models using LIVECell and evaluate model segmentation accuracy with a proposed a suite of benchmarks.
Durable tracking anti-SARS-CoV-2 antibodies in cancer patients recovered from COVID-19
Authors: Huang Yongsheng , Yu Jing , Li Dan , He Kai , Liu Wenyang , Wang Lin , Chen Yeshan , Xie Conghua , Wu Xiaowei
Published: August 2021

Cancer patients are more susceptible to SARS-CoV-2 infection and generally have higher mortality rate. Anti-SARS-CoV-2 IgG is an important consideration for the patients in this COVID-19 pandemic. Recent researches suggested the rapid decay of anti-SARS-CoV-2 antibodies in the general population, but the decline rate of the antibodies in cancer patients was unknown. In this observational study, we reported the clinical features of the 53 cancer patients infected by SARS-CoV-2 from Wuhan, China and tracked the presence of anti-SARS-CoV-2 antibodies in the patients for more than 12 months. We found the duration (days) of anti-SARS-CoV-2 IgG in the patients was significant longer in chemotherapy (mean: 175; range: 75 to 315) and radiotherapy groups (mean: 168; range: 85 to 265) than in non-chemo- or radio-therapy group (mean: 58; range: 21 to 123) after their recovery from COVID-19. We also used single-cell RNA sequencing to track the immunologic changes in a representative patient recovered  from COVID-19 and found that CD8 + effective T cells, memory B cells and plasma cells were persistently activated in the patient undergoing chemotherapy. Together, our findings show that chemotherapy and radiotherapy might be beneficial to extend the duration of anti-SARS-CoV-2 IgG.
Stepwise low concentration atropine for myopic control: a 10-year cohort study
Authors: Chuang Meng-Ni , Fang Po-Chiung , Wu Pei-Chang
Published: August 2021

The aim of this study was to analyze changes in refraction and evaluate the variables in school children who received atropine as myopic control for 10 years. Low-concentration atropine (0.05%) was prescribed initially, and the dose was increased in a stepwise manner if rapid myopic progression (≥ 0.5D per half year) was noted during the regular follow-up visit. 23 children with a mean age of 6.96 ± 1.07 years were included. The initial spherical equivalent was − 1.25 ± 0.84 D. The overall mean myopic progression was − 0.30 ± 0.27 D/year. Younger initial age, female, higher initial spherical equivalent and the need of higher concentration of atropine were found to be risk factors for myopic progression in multivariate mixed-effect analysis (p = 0.013, 0.017, 0.024 and 0.014). Children who kept using a lower concentration of atropine (≤ 0.1%) tended to have slower myopic progression throughout the 10-year course than those who shifted to higher concentrations (> 0.1%) (p ≤ 0.001). Stepwise low concentration of atropine might be effective for long-term myopic control in school students. Those who had poor response to lower concentration of atropine may have the risk of faster progression, even with high concentration of atropine. Additional or alternative treatment might be considered.
Factors contributing to spatial–temporal variations of observed oxygen concentration over the Qinghai-Tibetan Plateau
Authors: Shi Peijun , Chen Yanqiang , Zhang Gangfeng , Tang Haiping , Chen Zhi , Yu Deyong , Yang Jing , Ye Tao , Wang Jing’ai , Liang Shunlin , Ma Yonggui , Wu Jidong , Gong Peng
Published: August 2021

Oxygen (O2) is the most abundant molecule in the atmosphere after nitrogen. Previous studies have documented that oxygen concentration remains nearly constant (20.946%) at all altitudes. Here we show for the first time that oxygen concentration varies significantly from earlier consensus and shows strong spatial and seasonal differences. Field observations on the Qinghai-Tibetan Plateau (QTP) indicate oxygen concentration of 19.94–20.66% (2018, n = 80), 19.98–20.78% (2019,n = 166) and 19.97–20.73% (2020, n = 176), all statistically different from earlier reports (p < 0.001) and are lower than the nearly constant. The mean oxygen concentration in summer (20.47%) is 0.31% higher than that of winter (20.16%) (n = 53) at identical locations in 2019, sampled in the Qilian Mountains, northwest QTP. We used LMG (The Lindeman, Merenda and Gold) method to estimate the relative contributions of altitude, air temperature and vegetation index (Fractional Vegetation Cover, FVC and Leaf Area Index, LAI) to oxygen concentration, which are 47%, 32% and 3% (FVC, R2 = 82%); 45%, 30% and 7% (LAI, R2 = 82%), respectively. These findings provide a new perspective for in-depth understanding on population risk in high altitude regions in the context of global climate change, to ensure the health and safety of residents and tourists in high altitude regions and promoting the stability, prosperity and sustainable development of high-altitude regions worldwide.
Effects of water and nitrogen coupling on the photosynthetic characteristics, yield, and quality of Isatis indigotica
Authors: Wang Yucai , He Xiucheng , Li Fuqiang , Deng Haoliang , Wang Zeyi , Huang Caixia , Han Yi , Ba Yuchun , Lei Lian , Zhang Changlong
Published: August 2021

Isatis indigotica is a commercial medicinal crop that is widely cultivated with high water and nutrient application, in the arid areas of northwest China. Rational irrigation and nitrogen application are key factors for successful crop management. The objective of this study was to determine the effect of water and nitrogen coupling on the photosynthetic characteristics, yield, and quality of Isatis indigotica produced in northwestern China. Field trials were conducted for 2 consecutive years at an irrigation test station. Data on photosynthetic parameters, yield, and quality were collected from individual Isatis indigotica for each treatment during 2018–2019. The application of nitrogen significantly increased photosynthetic rates and yield under the same irrigation conditions. However, the yields were reduced in the excess water treatments (W3N1 and W3N2) and in the excess nitrogen treatments (W1N3, W2N3, and W3N3) in contrast to the optimum W2N2 treatment. Moreover, the quality indicators of the W2N2 treatment decreased compared with CK, which was due to water stress and more photoassimilates being available to the roots, but the effective quality index value could be effectively improved by greatly increasing the yield.
Changes in the epidemiological characteristics of human brucellosis in Shaanxi Province from 2008 to 2020
Authors: An Cui-hong , Liu Zhi-guo , Nie Shou-min , Sun Yang-xin , Fan Suo-ping , Luo Bo-yan , Li Zhenjun , Xu Ji-ru
Published: August 2021

In the present study, surveys of case numbers, constituent ratios, conventional biotyping, and multilocus sequence typing (MLST) were applied to characterize the incidence rate and epidemiological characteristics of human brucellosis in Shaanxi Province, China. A total of 12,215 human brucellosis cases were reported during 2008–2020, for an annual average incidence rate of 2.48/100,000. The most significant change was that the county numbers of reported cases increased from 36 in 2008 to 84 in 2020, with a geographic expansion trend from northern Shaanxi to Guanzhong, and southern Shaanxi regions; the incidence rate declined in previous epidemic northern Shaanxi regions while increasing each year in Guanzhong and southern Shaanxi regions such as Hancheng and Xianyang. The increased incidence was closely related to the development of large-scale small ruminants (goats and sheep) farms in Guanzhong and some southern Shaanxi regions. Another significant feature was that student cases (n = 261) were ranked second among all occupations, accounting for 2.14% of the total number of cases, with the majority due to drinking unsterilized goat milk. Three Brucella species were detected (B. melitensis (bv. 1, 2, 3 and variant), B. abortus bv. 3/6, and B. suis bv. 1) and were mainly distributed in the northern Shaanxi and Guanzhong regions. Three known STs (ST8, ST2, and ST14) were identified based on MLST analysis. The characteristics that had not changed were that B. melitensis strains belonging to the ST8 population were the dominant species and were observed in all nine regions during the examined periods. Strengthened human and animal brucellosis surveillance and restriction of the transfer of infected sheep (goats) as well as students avoiding drinking raw milk are suggested as optimal control strategies.
Transcriptional overlap links DNA hypomethylation with DNA hypermethylation at adjacent promoters in cancer
Authors: Fain Jean S. , Loriot Axelle , Diacofotaki Anna , Van Tongelen Aurélie , De Smet Charles
Published: August 2021

Tumor development involves alterations in DNA methylation patterns, which include both gains (hypermethylation) and losses (hypomethylation) in different genomic regions. The mechanisms underlying these two opposite, yet co-existing, alterations in tumors remain unclear. While studying the human MAGEA6/GABRA3 gene locus, we observed that DNA hypomethylation in tumor cells can lead to the activation of a long transcript (CT-GABRA3) that overlaps downstream promoters (GABRQ and GABRA3) and triggers their hypermethylation. Overlapped promoters displayed increases in H3K36me3, a histone mark deposited during transcriptional elongation and known to stimulate de novo DNA methylation. Consistent with such a processive mechanism, increases in H3K36me3 and DNA methylation were observed over the entire region covered by the CT-GABRA3 overlapping transcript. Importantly, experimental induction of CT-GABRA3 by depletion of DNMT1 DNA methyltransferase, resulted in a similar pattern of regional DNA hypermethylation. Bioinformatics analyses in lung cancer datasets identified other genomic loci displaying this process of coupled DNA hypo/hypermethylation, and some of these included tumor suppressor genes, e.g. RERG and PTPRO. Together, our work reveals that focal DNA hypomethylation in tumors can indirectly contribute to hypermethylation of nearby promoters through activation of overlapping transcription, and establishes therefore an unsuspected connection between these two opposite epigenetic alterations.
The pressure characteristics analysis of oil pulsation flow based on VMD
Authors: Liu Ge , Chen Bin
Published: August 2021

The pressure signal of oil pulsating flow is a kind of multi-component signal; in order to realise the effective separation of the multi-component pressure signal and extract its vibration characteristics, the pressure signal was decomposed by Variational Mode Decomposition (VMD). The slope criterion of the centre frequency is proposed to determine the number of components of VMD decomposition, and the method to judge the main components of the signal by energy value is proposed. The Hilbert envelope demodulation analysis was performed on the main components obtained. The results show that the proposed center frequency slope criterion method is effective in the VMD decomposition of the pressure signal of oil pulsating flow, which is used to decompose the pressure signal into 9 components. Four major components of the pressure signal are obtained by the correlation between each component and the pressure signal, and the energy value calculation of each component. The main component frequency of the pressure signal is one time, 6 times, 11 times and 14 times the frequency of the system spindle rotation; these are the sum of two cosine signals of close frequency and have the characteristic of beat vibration.
Influence of visual feedback persistence on visuo-motor skill improvement
Authors: Unell Alyssa , Eisenstat Zachary M. , Braun Ainsley , Gandhi Abhinav , Gilad-Gutnick Sharon , Ben-Ami Shlomit , Sinha Pawan
Published: August 2021

Towards the larger goal of understanding factors relevant for improving visuo-motor control, we investigated the role of visual feedback for modulating the effectiveness of a simple hand-eye training protocol. The regimen comprised a series of curve tracing tasks undertaken over a period of one week by neurologically healthy individuals with their non-dominant hands. Our three subject groups differed in the training they experienced: those who received ‘Persistent’ visual-feedback by seeing their hand and trace evolve in real-time superimposed upon the reference patterns, those who received ‘Non-Persistent’ visual-feedback seeing their hand movement but not the emerging trace, and a ‘Control’ group that underwent no training. Improvements in performance were evaluated along two dimensions—accuracy and steadiness, to assess visuo-motor and motor skills, respectively. We found that persistent feedback leads to a significantly greater improvement in accuracy than non-persistent feedback. Steadiness, on the other hand, benefits from training irrespective of the persistence of feedback. Our results not only demonstrate the feasibility of rapid visuo-motor learning in adulthood, but more specifically, the influence of visual veridicality and a critical role for dynamically emergent visual information.
Durability of antibody response to vaccination and surrogate neutralization of emerging variants based on SARS-CoV-2 exposure history
Authors: McDade Thomas W. , Demonbreun Alexis R. , Sancilio Amelia , Mustanski Brian , D’Aquila Richard T. , McNally Elizabeth M.
Published: August 2021

Two-dose messenger RNA vaccines against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are highly effective in preventing symptomatic COVID-19 infection. However, the durability of protection is not known, nor is the effectiveness against emerging viral variants. Additionally, vaccine responses may differ based on prior SARS-CoV-2 exposure history. To investigate protection against SARS-CoV-2 variants we measured binding and neutralizing antibody responses following both vaccine doses. We document significant declines in antibody levels three months post-vaccination, and reduced neutralization of emerging variants, highlighting the need to identify correlates of clinical protection to inform the timing of and indications for booster vaccination.
Author Correction: Identification, characterization and control of a sequence variant in monoclonal antibody drug product: a case study
Authors: Thakur Anushikha , Nagpal Rekha , Ghosh Avik Kumar , Gadamshetty Deepak , Nagapattinam Sirisha , Subbarao Malini , Rakshit Shreshtha , Padiyar Sneha , Sreenivas Suma , Govindappa Nagaraja , Pai Harish V. , Subbaraman Ramakrishnan Melarkode
Published: August 2021

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Specific features to differentiate Giant cell arteritis aortitis from aortic atheroma using FDG-PET/CT
Authors: Espitia Olivier , Schanus Jérémy , Agard Christian , Kraeber-Bodéré Françoise , Hersant Jeanne , Serfaty Jean-Michel , Jamet Bastien
Published: August 2021

Aortic wall 18F-fluorodeoxyglucose (FDG)-uptake does not allow differentiation of aortitis from atheroma, which is problematic in clinical practice for diagnosing large vessel vasculitis giant-cell arteritis (GCA) in elderly patients. The purpose of this study was to compare the FDG uptake characteristics of GCA aortitis and aortic atheroma using positron emission tomography/FDG computed tomography (FDG-PET/CT). This study compared FDG aortic uptake between patients with GCA aortitis and patients with aortic atheroma; previously defined by contrast enhanced CT. Visual grading according to standardized FDG-PET/CT interpretation criteria and semi-quantitative analyses (maximum standardized uptake value (SUVmax), delta SUV (∆SUV), target to background ratios (TBR)) of FDG aortic uptake were conducted. The aorta was divided into 5 segments for analysis. 29 GCA aortitis and 66 aortic atheroma patients were included. A grade 3 FDG uptake of the aortic wall was identified for 23 (79.3%) GCA aortitis patients and none in the atheroma patient group (p < 0.0001); grade 2 FDG uptake was as common in both populations. Of the 29 aortitis patients, FDG uptake of all 5 aortic segments was positive for 21 of them (72.4%, p < 0.0001). FDG uptake of the supra-aortic trunk was identified for 24 aortitis (82.8%) and no atheromatous cases (p < 0.0001). All semi-quantitative analyses of FDG aortic wall uptake (SUVmax, ∆SUV and TBRs) were significantly higher in the aortitis group. ∆SUV was the feature with the largest differential between aortitis and aortic atheroma. In this study, GCA aortitis could be distinguished from an aortic atheroma by the presence of an aortic wall FDG uptake grade 3, an FDG uptake of the 5 aortic segments, and FDG uptake of the peripheral arteries.
Whole genome sequencing of clinical samples reveals extensively drug resistant tuberculosis (XDR TB) strains from the Beijing lineage in Nigeria, West Africa
Authors: Olawoye Idowu B. , Uwanibe Jessica N. , Kunle-Ope Chioma N. , Davies-Bolorunduro Olabisi F. , Abiodun Temitope A. , Audu Rosemary A. , Salako Babatunde L. , Happi Christian T.
Published: August 2021

Multi-drug (MDR) and extensively drug-resistant (XDR) tuberculosis (TB) continues to be a global public health problem especially in high TB burden countries like Nigeria. Many of these cases are undetected and go on to infect high risk individuals. Clinical samples from positive rifampicin resistant Xpert®MTB/Rif assay were subjected to direct whole genome sequencing and bioinformatics analysis to identify the full antibiotics resistance and lineage profile. We report two (2) XDR TB samples also belonging to the East-Asian/Beijing family of lineage 2 Mycobacterium tuberculosis complex from clinical samples in Nigeria. Our findings further reveal the presence of mutations that confer resistance to first-line drugs (rifampicin, isoniazid, ethambutol and pyrazanimide), second-line injectables (capreomycin, streptomycin, kanamycin and/or amikacin) and at least one of the fluoroquinolones (ofloxacin, moxifloxacin, levofloxacin and/or ciprofloxacin) in both samples. The genomic sequence data from this study not only provide the first evidence of XDR TB in Nigeria and West Africa, but also emphasize the importance of WGS in accurately detecting MDR and XDR TB, to ensure adequate and proper management treatment regimens for affected individuals. This will greatly aid in preventing the spread of drug resistance TB in high burden countries.
Spatial and temporal VEGF receptor intracellular trafficking in microvascular and macrovascular endothelial cells
Authors: Silva Juliete A. F. , Qi Xiaoping , Grant Maria B. , Boulton Michael E.
Published: August 2021

The vascular endothelial growth factor receptors (VEGFRs) can shape the neovascular phenotype of vascular endothelial cells when translocated to the nucleus, however the spatial and temporal changes in the intracellular distribution and translocation of VEGFRs to the nucleus and the organelles involved in this process is unclear. This study reports the effect of exogenous VEGF on translocation of VEGFRs and organelles in micro- and macrovascular endothelial cells. We showed that VEGF is responsible for: a rapid and substantial nuclear translocation of VEGFRs; VEGFR1 and VEGFR2 exhibit distinct spatial, temporal and structural translocation characteristics both in vitro and in vivo and this determines the nuclear VEGFR1:VEGFR2 ratio which differs between microvascular and macrovascular cells; VEGFR2 nuclear translocation is associated with the endosomal pathway transporting the receptor from Golgi in microvascular endothelial cells; and an increase in the volume of intracellular organelles. In conclusion, the nuclear translocation of VEGFRs is both receptor and vessel (macro versus micro) dependent and the endosomal pathway plays a key role in the translocation of VEGFRs to the nucleus and the subsequent export to the lysosomal system. Modulating VEGF-mediated VEGFR1 and VEGFR2 intracellular transmigration pathways may offer an alternative for the development of new anti-angiogenic therapies.
Thermal discharge-induced seawater warming alters richness, community composition and interactions of bacterioplankton assemblages in a coastal ecosystem
Authors: Rajeev Meora , Sushmitha T. J. , Aravindraja Chairmandurai , Toleti Subba Rao , Pandian Shunmugiah Karutha
Published: August 2021

Despite accumulating evidence on the impact of global climate warming on marine microbes, how increasing seawater temperature influences the marine bacterioplankton communities is elusive. As temperature gradient created by thermal discharges provides a suitable in situ model to study the influence of warming on marine microorganisms, surface seawater were sampled consecutively for one year (September-2016 to August-2017) from the control (unimpacted) and thermal discharge-impacted areas of a coastal power plant, located in India. The bacterioplankton community differences between control (n = 16) and thermal discharge-impacted (n = 26) areas, as investigated using 16S rRNA gene tag sequencing revealed reduced richness and varied community composition at thermal discharge-impacted areas. The relative proportion of Proteobacteria was found to be higher (average ~ 15%) while, Bacteroidetes was lower (average ~ 10%) at thermal discharge-impacted areas. Intriguingly, thermal discharge-impacted areas were overrepresented by several potential pathogenic bacterial genera (e.g. Pseudomonas, Acinetobacter, Sulfitobacter, Vibrio) and other native marine genera (e.g. Marinobacter, Pseudoalteromonas, Alteromonas, Pseudidiomarina, Halomonas). Further, co-occurrence networks demonstrated that complexity and connectivity of networks were altered in warming condition. Altogether, results indicated that increasing temperature has a profound impact on marine bacterioplankton richness, community composition, and inter-species interactions. Our findings are immensely important in forecasting the consequences of future climate changes especially, ocean warming on marine microbiota.
Building a Chinese pan-genome of 486 individuals
Authors: Li Qiuhui , Tian Shilin , Yan Bin , Liu Chi Man , Lam Tak-Wah , Li Ruiqiang , Luo Ruibang
Published: August 2021

Pan-genome sequence analysis of human population ancestry is critical for expanding and better defining human genome sequence diversity. However, the amount of genetic variation still missing from current human reference sequences is still unknown. Here, we used 486 deep-sequenced Han Chinese genomes to identify 276 Mbp of DNA sequences that, to our knowledge, are absent in the current human reference. We classified these sequences into individual-specific and common sequences, and propose that the common sequence size is uncapped with a growing population. The 46.646 Mbp common sequences obtained from the 486 individuals improved the accuracy of variant calling and mapping rate when added to the reference genome. We also analyzed the genomic positions of these common sequences and found that they came from genomic regions characterized by high mutation rate and low pathogenicity. Our study authenticates the Chinese pan-genome as representative of DNA sequences specific to the Han Chinese population missing from the GRCh38 reference genome and establishes the newly defined common sequences as candidates to supplement the current human reference.
Ultrasensitive quantification of multiplexed mRNA variants via splice-junction anchored DNA probes and SplintR ligase-initiated PCR
Authors: Jia Yuting , Han Jun , Wang Hui , Hong Weixiang , Wang Honghong , Zhang Mai , Li Zhengping
Published: August 2021

A method was developed for multiplexed quantification of mRNA splicing variants via splice-junction anchored DNA probes and SplintR ligase-initiated PCR.
Enantioselective total synthesis of (+)-rubrobramide, (+)-talaramide A, and (−)-berkeleyamide D by a skeletal diversification strategy
Authors: Tanaka Kosaku , Kobayashi Kenichi , Kogen Hiroshi
Published: August 2021

A unified synthesis of (+)-rubrobramide, (+)-talaramide A, and (−)-berkeleyamide D was achieved from the vinylogous esters by a skeletal diversification strategy based on regioselective 5-exo or 6-endo cyclization.
Bipolar charge trapping for absorption enhancement in a graphene-based ultrathin dual-band terahertz biosensor
Authors: Varshney Gaurav , Giri Pushpa
Published: August 2021

Surface plasmons generated at the graphene dielectric interface can be altered by trapping the electric charge.
Amorphous Ta2O5-supported Ru as an efficient electrocatalyst for selective hydrogenation of cinnamaldehyde with water as the hydrogen source
Authors: Wu Tianxing , Meng Hanqi , Dang Rui
Published: August 2021

Amorphous Ta2O5-supported Ru as an efficient electrocatalyst for electrocatalytic selective hydrogenation of cinnamaldehyde.
Controlling the organization and stretchability of poly(3-butylthiophene) spherulites
Authors: Wei Nan , Zhu Bingyan , He Jiaxin , Shan Hongtao , Zhou Jianjun , Huo Hong
Published: August 2021

We prepare poly(3-butylthiophene) (P3BT) films with patterned spherulites by brushing the P3BT film surface and annealing with carbon disulfide vapor. The patterned films exhibit anisotropic cracking and large conductivity.
Topological floppy modes in models of epithelial tissues
Authors: Liu Harry , Zhou Di , Zhang Leyou , Lubensky David K. , Mao Xiaoming
Published: August 2021

We find mechanical topological phases in models of epithelial tissues with active tension on cell edges, where soft modes and stress distribution exhibit exponential localization to edges and interfaces of tissues.
Photo-switchable membranes constructed from graphene oxide/star-PDMS nanocomposites for gas permeation control
Authors: Alrayyes Abdalrahman U. , Hu Yaoxin , Tabor Rico F. , Wang Huanting , Saito Kei
Published: August 2021

The article presents the first light-responsive, ultra-thin membrane that utilises graphene-based nanosheets as a nanofiller. By using a star-PDMS as the polymer phase, the membrane exhibited efficient and continuous permeance regulation by UV light.
An adaptive edge element method and its convergence for an electromagnetic constrained optimal control problem
Authors: Li Bowen , Zou Jun
Published: August 2021

In this work, an adaptive edge element method is developed for anH(curl)-elliptic constrained optimal control problem. We use the lowest-order Nédélec’s edge elements of first family and the piecewise (element-wise) constant functions to approximate the state and the control, respectively, and propose a new adaptive algorithm with error estimators involving both residual-type error estimators and lower-order data oscillations. By using a local regular decomposition forH(curl)-functions and the standard bubble function techniques, we derive thea posteriorierror estimates for the proposed error estimators. Then we exploit the convergence properties of the orthogonalL2-projections and the mesh-size functions to demonstrate that the sequences of the discrete states and controls generated by the adaptive algorithm converge strongly to the exact solutions of the state and control in the energy-norm andL2-norm, respectively, by first achieving the strong convergence towards the solution to a limiting control problem. Three-dimensional numerical experiments are also presented to confirm our theoretical results and the quasi-optimality of the adaptive edge element method.
Zystische zervikale Lymphknotenschwellung – TG-Bestimmung im Punktat sichert das lymphatisch metastasierte papilläre Schilddrüsenkarzinom
Authors: Smaxwil Constantin , Esianu Eduard , Altmeier Julia , Zielke Andreas
Published: August 2021

Anamnese Eine Patientin stellte sich mit einer zystischen Raumforderung im seitlichen Halsdreieck vor.

Untersuchung und Diagnostik Nach Ultraschall und MRT wurde eine Feinnadelpunktion durchgeführt. Zytologisch fanden sich keine malignitätsverdächtigen Zellen. Bei einer erneuten Punktion wurde nun auch das Thyreoglobulin in der Zystenflüssigkeit bestimmt – und stark erhöht nachgewiesen. Damit war das lymphatisch metastasierte Schilddrüsenkarzinom gesichert.

Therapie und Verlauf Die erforderliche Operation konnte einzeitig durchgeführt werden. Drei Wochen nach der Operation erfolgte die Radiojodtherapie mit 3,7GBq I131.

Folgerung Schwellungen der Halslymphknoten können viele Gründe haben, dabei selten auch einmal die Metastase eines Schilddrüsenkarzinoms sein. Wir stellen anhand eines Fallbeispiels einen einfachen Weg vor, der das lymphatisch metastasierte Schilddrüsenkarzinom sicher nachweisen kann.