bluuebunny/crossref_metadata_2025 huggingface dataset:
A Study of the Performances of Widely Used External Magnetic Field Models in the Outer Zone of the Earth's Radiation Belts by Comparing the Field Observations From Van Allen Probe‐A and the Model Estimations
Authors: Yang Xiaochao , Wang Li
Published: December 2021

Using magnetic field observations from Van Allen Probe‐A (VAP‐A), we evaluated the performances of 13 widely used external magnetic field models in the Earth's outer radiation belt region in detail. It is shown that later models tend to match observations better than earlier models except for T03s, which has a top performance similar to the latest TA16_RBF model. Additionally, in its applicable domain from quiet to moderately disturbed geomagnetic conditions, T02 has comparable performance to T03s. In the dusk, dawn and night sectors, highly stretched magnetic fields are seen in both the observations and model output between LmIGRF ∼5.7 and 6.1, which suggests the existence of steep radial gradients in the plasma pressures inside the outer belt region. The contributions from the currents located in the dusk sector during a disturbed period, such as the partial ring current and the substorm current wedge, are not adequately accounted for by the models, and the contribution of field‐aligned currents may also be underestimated. The results of this study will help select reliable external field models for future radiation belt studies and help assess uncertainties caused by the selected models. In addition, detailed analysis of the field components depicted by the empirical models could shed light on understanding the contributions from different current systems in this region.
miR-181a is a novel player in the STAT3-mediated survival network of TCRαβ+ CD8+ T large granular lymphocyte leukemia
Authors: Assmann Jorn L. J. C. , Leon Leticia G. , Stavast Christiaan J. , van den Bogaerdt Sanne E. , Schilperoord-Vermeulen Joyce , Sandberg Yorick , Bellido Mar , Erkeland Stefan J. , Feith David J. , Loughran Jr Thomas P. , Langerak Anton W.
Published: December 2021

T-LGL cells arise as a consequence of chronic antigenic stimulation and inflammation and thrive because of constitutive activation of the STAT3 and ERK pathway. Notably, in 40% of patients, constitutive STAT3 activation is due to STAT3 activating mutations, whereas in 60% this is unknown. As miRNAs are amongst the most potent regulators in health and disease, we hypothesized that aberrant miRNA expression could contribute to dysregulation of these pathways. miRNA sequencing in T-LGL leukemia cases and aged-matched healthy control TEMRA cells revealed overexpression of miR-181a. Furthermore, geneset enrichment analysis (GSEA) of downregulated targets of miR-181a implicated involvement in regulating STAT3 and ERK1/2 pathways. Flow cytometric analyses showed increased SOCS3+ and DUSP6+ T-LGL cells upon miR-181a inhibition. In addition, miR-181a-transfected human CD8+ T cells showed increased basal STAT3 and ERK1/2 phosphorylation. By using TL1, a human T-LGL cell line, we could show that miR-181a is an actor in T-LGL leukemia, driving STAT3 activation by SOCS3 inhibition and ERK1/2 phosphorylation by DUSP6 inhibition and verified this mechanism in an independent cell line. In addition, miR-181a inhibition resulted in a higher sensitivity to FAS-mediated apoptosis. Collectively, our data show that miR-181a could be the missing link to explain why STAT3-unmutated patients show hyperactive STAT3.
Lipid droplets as endogenous intracellular microlenses
Authors: Chen Xixi , Wu Tianli , Gong Zhiyong , Guo Jinghui , Liu Xiaoshuai , Zhang Yao , Li Yuchao , Ferraro Pietro , Li Baojun
Published: December 2021

Using a single biological element as a photonic component with well-defined features has become a new intriguing paradigm in biophotonics. Here we show that endogenous lipid droplets in the mature adipose cells can behave as fully biocompatible microlenses to strengthen the ability of microscopic imaging as well as detecting intra- and extracellular signals. By the assistance of biolenses made of the lipid droplets, enhanced fluorescence imaging of cytoskeleton, lysosomes, and adenoviruses has been achieved. At the same time, we demonstrated that the required excitation power can be reduced by up to 73%. The lipidic microlenses are finely manipulated by optical tweezers in order to address targets and perform their real-time imaging inside the cells. An efficient detecting of fluorescence signal of cancer cells in extracellular fluid was accomplished due to the focusing effect of incident light by the lipid droplets. The lipid droplets acting as endogenous intracellular microlenses open the intriguing route for a multifunctional biocompatible optics tool for biosensing, endoscopic imaging, and single-cell diagnosis.
Relationship between sensory characteristics and cortical thickness/volume in autism spectrum disorders
Authors: Habata Kaie , Cheong Yongjeon , Kamiya Taku , Shiotsu Daichi , Omori Ichiro M. , Okazawa Hidehiko , Jung Minyoung , Kosaka Hirotaka
Published: December 2021

Individuals with autism spectrum disorders (ASDs) exhibit atypical sensory characteristics, impaired social skills, deficits in verbal and nonverbal communication, and restricted and repetitive behaviors. The relationship between sensory characteristics and brain morphological changes in ASD remains unclear. In this study, we investigated the association between brain morphological changes and sensory characteristics in individuals with ASD using brain image analysis and a sensory profile test. Forty-three adults with ASD and 84 adults with typical development underwent brain image analysis using FreeSurfer. The brain cortex was divided into 64 regions, and the cortical thickness and volume of the limbic system were calculated. The sensory characteristics of the participants were evaluated using the Adolescent/Adult Sensory Profile (AASP). Correlation analysis was performed for cortical thickness, limbic area volume, and AASP scores. In the ASD group, there was a significant positive correlation between visual sensory sensitivity scores and the right lingual cortical thickness (r = 0.500). There were also significant negative correlations between visual sensation avoiding scores and the right lateral orbitofrontal cortical thickness (r = −0.513), taste/smell sensation avoiding scores and the right hippocampal volume (r = −0.510), and taste/smell sensation avoiding scores and the left hippocampal volume (r = −0.540). The study identified associations among the lingual cortical thickness, lateral orbitofrontal cortical thickness, and hippocampal volume and sensory characteristics. These findings suggest that brain morphological changes may trigger sensory symptoms in adults with ASD.
Moderators of inflammation-related depression: a prospective study of breast cancer survivors
Authors: Manigault Andrew W. , Ganz Patricia A. , Irwin Michael R. , Cole Steve W. , Kuhlman Kate R. , Bower Julienne E.
Published: December 2021

Inflammation has been shown to predict depression, but sensitivity to inflammation varies across individuals. Experimental studies administering potent pro-inflammatory agents have begun to characterize this sensitivity. However, risk factors for inflammation-associated depression in naturalistic contexts have not been determined. The present study examined key psychological and behavioral risk factors (state anxiety, perceived stress, negative affect, disturbed sleep, and childhood adversity) as potential moderators of the relationship between inflammation and depressive symptoms in a prospective longitudinal study of breast cancer survivors. Women with early stage breast cancer were recruited after completing primary cancer treatment (nfinal = 161). Depressive symptoms, inflammatory markers (CRP, IL-6, and sTNF-RII), and key risk factors were assessed post treatment (T1), at 6 and 12-month follow-ups (T2 and T3), and during a final follow-up (TF) 3−6 years after T1; childhood adversity was measured only at T3. Inflammatory markers were combined into a single inflammatory index prior to analyses. Women who reported higher levels of state anxiety, perceived stress, negative affect, and/or sleep disturbance at T1 (post-treatment) exhibited higher depressive symptoms at times when inflammation was higher than typical (interaction βs ranged from .06 to .08; all ps < .014). Results demonstrate the relevance of these risk factors for understanding inflammation-associated depression in a clinical context and could inform targeted strategies for prevention and treatment among at-risk populations.
Second sound in the crossover from the Bose-Einstein condensate to the Bardeen-Cooper-Schrieffer superfluid
Authors: Hoffmann Daniel K. , Singh Vijay Pal , Paintner Thomas , Jäger Manuel , Limmer Wolfgang , Mathey Ludwig , Hecker Denschlag Johannes
Published: December 2021

Second sound is an entropy wave which propagates in the superfluid component of a quantum liquid. Because it is an entropy wave, it probes the thermodynamic properties of the quantum liquid. Here, we study second sound propagation for a large range of interaction strengths within the crossover between a Bose-Einstein condensate (BEC) and the Bardeen-Cooper-Schrieffer (BCS) superfluid, extending previous work at unitarity. In particular, we investigate the strongly-interacting regime where currently theoretical predictions only exist in terms of an interpolation in the crossover. Working with a quantum gas of ultracold fermionic 6Li atoms with tunable interactions, we show that the second sound speed varies only slightly in the crossover regime. By varying the excitation procedure, we gain deeper insight on sound propagation. We compare our measurement results with classical-field simulations, which help with the interpretation of our experiments.
The histologic phenotype of lung cancers is associated with transcriptomic features rather than genomic characteristics
Authors: Tang Ming , Abbas Hussein A. , Negrao Marcelo V. , Ramineni Maheshwari , Hu Xin , Hubert Shawna Marie , Fujimoto Junya , Reuben Alexandre , Varghese Susan , Zhang Jianhua , Li Jun , Chow Chi-Wan , Mao Xizeng , Song Xingzhi , Lee Won-Chul , Wu Jia , Little Latasha , Gumbs Curtis , Behrens Carmen , Moran Cesar , Weissferdt Annikka , Lee J. Jack , Sepesi Boris , Swisher Stephen , Cheng Chao , Kurie Jonathan , Gibbons Don , Heymach John V. , Wistuba Ignacio I. , Futreal P. Andrew , Kalhor Neda , Zhang Jianjun
Published: December 2021

Histology plays an essential role in therapeutic decision-making for lung cancer patients. However, the molecular determinants of lung cancer histology are largely unknown. We conduct whole-exome sequencing and microarray profiling on 19 micro-dissected tumor regions of different histologic subtypes from 9 patients with lung cancers of mixed histology. A median of 68.9% of point mutations and 83% of copy number aberrations are shared between different histologic components within the same tumors. Furthermore, different histologic components within the tumors demonstrate similar subclonal architecture. On the other hand, transcriptomic profiling reveals shared pathways between the same histologic subtypes from different patients, which is supported by the analyses of the transcriptomic data from 141 cell lines and 343 lung cancers of different histologic subtypes. These data derived from mixed histologic subtypes in the setting of identical genetic background and exposure history support that the histologic fate of lung cancer cells is associated with transcriptomic features rather than the genomic profiles in most tumors.
Breaking the barrier to biomolecule limit-of-detection via 3D printed multi-length-scale graphene-coated electrodes
Authors: Ali Md. Azahar , Hu Chunshan , Yuan Bin , Jahan Sanjida , Saleh Mohammad S. , Guo Zhitao , Gellman Andrew J. , Panat Rahul
Published: December 2021

Sensing of clinically relevant biomolecules such as neurotransmitters at low concentrations can enable an early detection and treatment of a range of diseases. Several nanostructures are being explored by researchers to detect biomolecules at sensitivities beyond the picomolar range. It is recognized, however, that nanostructuring of surfaces alone is not sufficient to enhance sensor sensitivities down to the femtomolar level. In this paper, we break this barrier/limit by introducing a sensing platform that uses a multi-length-scale electrode architecture consisting of 3D printed silver micropillars decorated with graphene nanoflakes and use it to demonstrate the detection of dopamine at a limit-of-detection of 500 attomoles. The graphene provides a high surface area at nanoscale, while micropillar array accelerates the interaction of diffusing analyte molecules with the electrode at low concentrations. The hierarchical electrode architecture introduced in this work opens the possibility of detecting biomolecules at ultralow concentrations.
Highly efficient ethylene production via electrocatalytic hydrogenation of acetylene under mild conditions
Authors: Wang Suheng , Uwakwe Kelechi , Yu Liang , Ye Jinyu , Zhu Yuezhou , Hu Jingting , Chen Ruixue , Zhang Zheng , Zhou Zhiyou , Li Jianfeng , Xie Zhaoxiong , Deng Dehui
Published: December 2021

Renewable energy-based electrocatalytic hydrogenation of acetylene to ethylene (E-HAE) under mild conditions is an attractive substitution to the conventional energy-intensive industrial process, but is challenging due to its low Faradaic efficiency caused by competitive hydrogen evolution reaction. Herein, we report a highly efficient and selective E-HAE process at room temperature and ambient pressure over the Cu catalyst. A high Faradaic efficiency of 83.2% for ethylene with a current density of 29 mA cm−2 is reached at −0.6 V vs. the reversible hydrogen electrode. In-situ spectroscopic characterizations combined with first-principles calculations reveal that electron transfer from the Cu surface to adsorbed acetylene induces preferential adsorption and hydrogenation of the acetylene over hydrogen formation, thus enabling a highly selective E-HAE process through the electron-coupled proton transfer mechanism. This work presents a feasible route for high-efficiency ethylene production from E-HAE.
Reductive inactivation of the hemiaminal pharmacophore for resistance against tetrahydroisoquinoline antibiotics
Authors: Wen Wan-Hong , Zhang Yue , Zhang Ying-Ying , Yu Qian , Jiang Chu-Chu , Tang Man-Cheng , Pu Jin-Yue , Wu Lian , Zhao Yi-Lei , Shi Ting , Zhou Jiahai , Tang Gong-Li
Published: December 2021

Antibiotic resistance is becoming one of the major crises, among which hydrolysis reaction is widely employed by bacteria to destroy the reactive pharmacophore. Correspondingly, antibiotic producer has canonically co-evolved this approach with the biosynthetic capability for self-resistance. Here we discover a self-defense strategy featuring with reductive inactivation of hemiaminal pharmacophore by short-chain dehydrogenases/reductases (SDRs) NapW and homW, which are integrated with the naphthyridinomycin biosynthetic pathway. We determine the crystal structure of NapW·NADPH complex and propose a catalytic mechanism by molecular dynamics simulation analysis. Additionally, a similar detoxification strategy is identified in the biosynthesis of saframycin A, another member of tetrahydroisoquinoline (THIQ) antibiotics. Remarkably, similar SDRs are widely spread in bacteria and able to inactive other THIQ members including the clinical anticancer drug, ET-743. These findings not only fill in the missing intracellular events of temporal-spatial shielding mode for cryptic self-resistance during THIQs biosynthesis, but also exhibit a sophisticated damage-control in secondary metabolism and general immunity toward this family of antibiotics.
Nickel-catalyzed electrochemical carboxylation of unactivated aryl and alkyl halides with CO2
Authors: Sun Guo-Quan , Zhang Wei , Liao Li-Li , Li Li , Nie Zi-Hao , Wu Jin-Gui , Zhang Zhen , Yu Da-Gang
Published: December 2021

Electrochemical catalytic reductive cross couplings are powerful and sustainable methods to construct C−C bonds by using electron as the clean reductant. However, activated substrates are used in most cases. Herein, we report a general and practical electro-reductive Ni-catalytic system, realizing the electrocatalytic carboxylation of unactivated aryl chlorides and alkyl bromides with CO2. A variety of unactivated aryl bromides, iodides and sulfonates can also undergo such a reaction smoothly. Notably, we also realize the catalytic electrochemical carboxylation of aryl (pseudo)halides with CO2avoiding the use of sacrificial electrodes. Moreover, this sustainable and economic strategy with electron as the clean reductant features mild conditions, inexpensive catalyst, safe and cheap electrodes, good functional group tolerance and broad substrate scope. Mechanistic investigations indicate that the reaction might proceed via oxidative addition of aryl halides to Ni(0) complex, the reduction of aryl-Ni(II) adduct to the Ni(I) species and following carboxylation with CO2.
Geomorphic contexts and science focus of the Zhurong landing site on Mars
Authors: Liu Jianjun , Li Chunlai , Zhang Rongqiao , Rao Wei , Cui Xiaofeng , Geng Yan , Jia Yang , Huang Hai , Ren Xin , Yan Wei , Zeng Xingguo , Wen Weibin , Wang Xing , Gao Xingye , Fu Qiang , Zhu Yan , Dong Jihong , Li Haitao , Wang Xianzhong , Zuo Wei , Su Yan , Kong Deqing , Zhang Hongbo
Published: December 2021

As part of the Tianwen-1 mission, the Zhurong rover successfully touched down in southern Utopia Planitia on 15 May 2021. On the basis of the new sub-metre-resolution images from the High Resolution Imaging Camera on board the Tianwen-1 orbiter, we determined that the Zhurong rover landed at 109.925° E, 25.066° N at an elevation of −4,099.4 m. The landing site is near the highland–lowland boundary1 and multiple suspected shorelines2–7. Under the guidance of the remote sensing survey, the Zhurong rover is travelling south for specific in situ investigation. Supported by the six payloads on board the rover8, its initial key targets are rocks, rocky fields, transverse aeolian ridges and subsurface structures along the path. Extended investigation will aim at troughs and cones in the distance. A better understanding of the formation mechanisms of these targets may shed light on the historical volcanism and water/ice activities within the landing area, as well as the activities of the wind. These results may reveal the characteristics and evolution of the ancient Martian environment and advance the exploration of the habitability of ancient Mars.
Non-equilibrium conditions inside rock pores drive fission, maintenance and selection of coacervate protocells
Authors: Ianeselli Alan , Tetiker Damla , Stein Julian , Kühnlein Alexandra , Mast Christof B. , Braun Dieter , Dora Tang T.-Y.
Published: December 2021

Key requirements for the first cells on Earth include the ability to compartmentalize and evolve. Compartmentalization spatially localizes biomolecules from a dilute pool and an evolving cell, which, as it grows and divides, permits mixing and propagation of information to daughter cells. Complex coacervate microdroplets are excellent candidates as primordial cells with the ability to partition and concentrate molecules into their core and support primitive and complex biochemical reactions. However, the evolution of coacervate protocells by fusion, growth and fission has not yet been demonstrated. In this work, a primordial environment initiated the evolution of coacervate-based protocells. Gas bubbles inside heated rock pores perturb the coacervate protocell distribution and drive the growth, fusion, division and selection of coacervate microdroplets. Our findings provide a compelling scenario for the evolution of membrane-free coacervate microdroplets on the early Earth, induced by common gas bubbles within heated rock pores.
Colossal magnetic fields in high refractive index materials at microwave frequencies
Authors: Luk`yanchuk B. , Vasilyak L. M. , Pecherkin V. Ya. , Vetchinin S. P. , Fortov V. E. , Wang Z. B. , Paniagua-Domínguez R. , Fedyanin A. A.
Published: December 2021

Resonant scattering of electromagnetic waves is a widely studied phenomenon with a vast range of applications that span completely different fields, from astronomy or meteorology to spectroscopy and optical circuitry. Despite being subject of intensive research for many decades, new fundamental aspects are still being uncovered, in connection with emerging areas, such as metamaterials and metasurfaces or quantum and topological optics, to mention some. In this work, we demonstrate yet one more novel phenomenon arising in the scattered near field of medium sized objects comprising high refractive index materials, which allows the generation of colossal local magnetic fields. In particular, we show that GHz radiation illuminating a high refractive index ceramic sphere creates instant magnetic near-fields comparable to those in neutron stars, opening up a new paradigm for creation of giant magnetic fields on the millimeter's scale.
Comparison of an improved self-consistent lower bound theory with Lehmann’s method for low-lying eigenvalues
Authors: Ronto Miklos , Pollak Eli , Martinazzo Rocco
Published: December 2021

Ritz eigenvalues only provide upper bounds for the energy levels, while obtaining lower bounds requires at least the calculation of the variances associated with these eigenvalues. The well-known Weinstein and Temple lower bounds based on the eigenvalues and variances converge very slowly and their quality is considerably worse than that of the Ritz upper bounds. Lehmann presented a method that in principle optimizes Temple’s lower bounds with significantly improved results. We have recently formulated a Self-Consistent Lower Bound Theory (SCLBT), which improves upon Temple’s results. In this paper, we further improve the SCLBT and compare its quality with Lehmann’s theory. The Lánczos algorithm for constructing the Hamiltonian matrix simplifies Lehmann’s theory and is essential for the SCLBT method. Using two lattice Hamiltonians, we compared the improved SCLBT (iSCLBT) with its previous implementation as well as with Lehmann’s lower bound theory. The novel iSCLBT exhibits a significant improvement over the previous version. Both Lehmann’s theory and the SCLBT variants provide significantly better lower bounds than those obtained from Weinstein’s and Temple’s methods. Compared to each other, the Lehmann and iSCLBT theories exhibit similar performance in terms of the quality and convergence of the lower bounds. By increasing the number of states included in the calculations, the lower bounds are tighter and their quality becomes comparable with that of the Ritz upper bounds. Both methods are suitable for providing lower bounds for low-lying excited states as well. Compared to Lehmann’s theory, one of the advantages of the iSCLBT method is that it does not necessarily require the Weinstein lower bound for its initial input, but Ritz eigenvalue estimates can also be used. Especially owing to this property the iSCLBT method sometimes exhibits improved convergence compared to that of Lehmann’s lower bounds
reString: an open-source Python software to perform automatic functional enrichment retrieval, results aggregation and data visualization
Authors: Manzini Stefano , Busnelli Marco , Colombo Alice , Franchi Elsa , Grossano Pasquale , Chiesa Giulia
Published: December 2021

Functional enrichment analysis is an analytical method to extract biological insights from gene expression data, popularized by the ever-growing application of high-throughput techniques. Typically, expression profiles are generated for hundreds to thousands of genes/proteins from samples belonging to two experimental groups, and after ad-hoc statistical tests, researchers are left with lists of statistically significant entities, possibly lacking any unifying biological theme. Functional enrichment tackles the problem of putting overall gene expression changes into a broader biological context, based on pre-existing knowledge bases of reference: database collections of known expression regulation, relationships and molecular interactions. STRING is among the most popular tools, providing both protein–protein interaction networks and functional enrichment analysis for any given set of identifiers. For complex experimental designs, manually retrieving, interpreting, analyzing and abridging functional enrichment results is a daunting task, usually performed by hand by the average wet-biology researcher. We have developed reString, a cross-platform software that seamlessly retrieves from STRING functional enrichments from multiple user-supplied gene sets, with just a few clicks, without any need for specific bioinformatics skills. Further, it aggregates all findings into human-readable table summaries, with built-in features to easily produce user-customizable publication-grade clustermaps and bubble plots. Herein, we outline a complete reString protocol, showcasing its features on a real use-case.
A proof of concept study on real-time LiMAx CYP1A2 liver function assessment of donor grafts during normothermic machine perfusion
Authors: Schurink Ivo J. , de Haan Jubi E. , Willemse Jorke , Mueller Matteo , Doukas Michael , Roest Henk , de Goeij Femke H. C. , Polak Wojciech G. , Ijzermans Jan N. M. , Dutkowski Philipp , van der Laan Luc J. W. , de Jonge Jeroen
Published: December 2021

No single reliable parameter exists to assess liver graft function of extended criteria donors during ex-vivo normothermic machine perfusion (NMP). The liver maximum capacity (LiMAx) test is a clinically validated cytochromal breath test, measuring liver function based on 13CO2 production. As an innovative concept, we aimed to integrate the LiMAx breath test with NMP to assess organ function. Eleven human livers were perfused using NMP. After one hour of stabilization, LiMAx testing was performed. Injury markers (ALT, AST, miR-122, FMN, and Suzuki-score) and lactate clearance were measured and related to LiMAx values. LiMAx values ranged between 111 and 1838 µg/kg/h, and performing consecutive LiMAx tests during longer NMP was feasible. No correlation was found between LiMAx value and miR-122 and FMN levels in the perfusate. However, a significant inverse correlation was found between LiMAx value and histological injury (Suzuki-score, R = − 0.874, P < 0.001), AST (R = − 0.812, P = 0.004) and ALT (R = − 0.687, P = 0.028). Furthermore, a significant correlation was found with lactate clearance (R = 0.683, P = 0.043). We demonstrate, as proof of principle, that liver function during NMP can be quantified using the LiMAx test, illustrating a positive correlation with traditional injury markers. This new breath-test application separates livers with adequate cytochromal liver function from inadequate ones and may support decision-making in the safe utilization of extended criteria donor grafts.
iTRAQ-based quantitative proteome analysis insights into cold stress of Winter Rapeseed (Brassica rapa L.) grown in the field
Authors: Niu Zaoxia , Liu Lijun , Pu Yuanyuan , Ma Li , Wu Junyan , Hu Fangdi , Fang Yan , Li Xuecai , Sun Wancang , Wang Wangtian , Bai Chunsheng
Published: December 2021

Winter rapeseed (Brassica rapaL.) is a major oilseed crop in Northern China, where its production was severely affected by chilling and freezing stress. However, not much is known about the role of differentially accumulated proteins (DAPs) during the chilling and freezing stress. In this study, isobaric tag for relative and absolute quantification (iTRAQ) technology was performed to identify DAPs under freezing stress. To explore the molecular mechanisms of cold stress tolerance at the cellular and protein levels, the morphological and physiological differences in the shoot apical meristem (SAM) of two winter rapeseed varieties, Longyou 7 (cold-tolerant) and Lenox (cold-sensitive), were explored in field-grown plants. Compared to Lenox, Longyou 7 had a lower SAM height and higher collar diameter. The level of malondialdehyde (MDA) and indole-3-acetic acid (IAA) content was also decreased. Simultaneously, the soluble sugars (SS) content, superoxide dismutase (SOD) activity, peroxidase (POD) activity, soluble protein (SP) content, and collar diameter were increased in Longyou 7 as compared to Lenox. A total of 6330 proteins were identified. Among this, 98, 107, 183 and 111 DAPs were expressed in L7 CK/Le CK, L7 d/Le d, Le d/Le CK and L7 d/L7 CK, respectively. Quantitative real-time PCR (RT-qPCR) analysis of the coding genes for seventeen randomly selected DAPs was performed for validation. These DAPs were identified based on gene ontology enrichment analysis, which revealed that glutathione transferase activity, carbohydrate-binding, glutathione binding, metabolic process, and IAA response were closely associated with the cold stress response. In addition, some cold-induced proteins, such as glutathione S-transferase phi 2(GSTF2), might play an essential role during cold acclimation in the SAM ofBrassica rapa. The present study provides valuable information on the involvement of DAPs during cold stress responses inBrassica rapaL, and hence could be used for breeding experiments.
Adaptive value of foot-and-mouth disease virus capsid substitutions with opposite effects on particle acid stability
Authors: Caridi Flavia , Cañas-Arranz Rodrigo , Vázquez-Calvo Ángela , de León Patricia , Calderón Katherine I. , Domingo Esteban , Sobrino Francisco , Martín-Acebes Miguel A.
Published: December 2021

Foot-and-mouth disease virus (FMDV) is a picornavirus that exhibits an extremely acid sensitive capsid. This acid lability is directly related to its mechanism of uncoating triggered by acidification inside cellular endosomes. Using a collection of FMDV mutants we have systematically analyzed the relationship between acid stability and the requirement for acidic endosomes using ammonium chloride (NH4Cl), an inhibitor of endosome acidification. A FMDV mutant carrying two substitutions with opposite effects on acid-stability (VP3 A116V that reduces acid stability, and VP1 N17D that increases acid stability) displayed a rapid shift towards acid lability that resulted in increased resistance to NH4Cl as well as to concanamicyn A, a different lysosomotropic agent. This resistance could be explained by a higher ability of the mutant populations to produce NH4Cl-resistant variants, as supported by their tendency to accumulate mutations related to NH4Cl-resistance that was higher than that of the WT populations. Competition experiments also indicated that the combination of both amino acid substitutions promoted an increase of viral fitness that likely contributed to NH4Cl resistance. This study provides novel evidences supporting that the combination of mutations in a viral capsid can result in compensatory effects that lead to fitness gain, and facilitate space to an inhibitor of acid-dependent uncoating. Thus, although drug-resistant variants usually exhibit a reduction in viral fitness, our results indicate that compensatory mutations that restore this reduction in fitness can promote emergence of resistance mutants.
Power efficient refined seizure prediction algorithm based on an enhanced benchmarking
Authors: Wang Ziyu , Yang Jie , Wu Hemmings , Zhu Junming , Sawan Mohamad
Published: December 2021

Deep learning techniques have led to significant advancements in seizure prediction research. However, corresponding used benchmarks are not uniform in published results. Moreover, inappropriate training and evaluation processes used in various work create overfitted models, making prediction performance fluctuate or unreliable. In this study, we analyzed the various data preparation methods, dataset partition methods in related works, and explained the corresponding impacts to the prediction algorithms. Then we applied a robust processing procedure that considers the appropriate sampling parameters and the leave-one-out cross-validation method to avoid possible overfitting and provide prerequisites for ease benchmarking. Moreover, a deep learning architecture takes advantage of a one-dimension convolutional neural network and a bi-directional long short-term memory network is proposed for seizure prediction. The architecture achieves 77.6% accuracy, 82.7% sensitivity, and 72.4% specificity, and it outperforms the indicators of other prior-art works. The proposed model is also hardware friendly; it has 6.274 k parameters and requires only 12.825 M floating-point operations, which is advantageous for memory and power constrained device implementations.
Effect of public corruption on the COVID-19 immunization progress
Authors: Farzanegan Mohammad Reza , Hofmann Hans Philipp
Published: December 2021

The coronavirus disease (COVID-19) outbreak has resulted in the death of over four million people since late 2019. To reduce the human and economic costs of COVID-19, different vaccines have been developed and distributed across countries. There has been significant cross-country variation in the vaccination of people against COVID-19. In this study, we focus on public corruption to explain the significant cause of cross-country variation in immunization progress. We suggest that countries with a higher degree of public corruption have been less successful in the vaccination of their population, controlling for other important determinants of immunization progress.
Molecular drivers of tumor progression in microsatellite stable APC mutation-negative colorectal cancers
Authors: Grant Adam , Xicola Rosa M. , Nguyen Vivian , Lim James , Thorne Curtis , Salhia Bodour , Llor Xavier , Ellis Nathan , Padi Megha
Published: December 2021

The tumor suppressor gene adenomatous polyposis coli (APC) is the initiating mutation in approximately 80% of all colorectal cancers (CRC), underscoring the importance of aberrant regulation of intracellular WNT signaling in CRC development. Recent studies have found that early-onset CRC exhibits an increased proportion of tumors lacking an APC mutation. We set out to identify mechanisms underlying APC mutation-negative (APCmut–) CRCs. We analyzed data from The Cancer Genome Atlas to compare clinical phenotypes, somatic mutations, copy number variations, gene fusions, RNA expression, and DNA methylation profiles between APCmut– and APC mutation-positive (APCmut+) microsatellite stable CRCs. Transcriptionally, APCmut– CRCs clustered into two approximately equal groups. Cluster One was associated with enhanced mitochondrial activation. Cluster Two was strikingly associated with genetic inactivation or decreased RNA expression of the WNT antagonist RNF43, increased expression of the WNT agonist RSPO3, activating mutation of BRAF, or increased methylation and decreased expression of AXIN2. APCmut– CRCs exhibited evidence of increased immune cell infiltration, with significant correlation between M2 macrophages and RSPO3. APCmut– CRCs comprise two groups of tumors characterized by enhanced mitochondrial activation or increased sensitivity to extracellular WNT, suggesting that they could be respectively susceptible to inhibition of these pathways.
A 1-minute blood test detects decreased immune function and increased clinical risk in COVID-19 patients
Authors: Deb Chirajyoti , Salinas Allan N. , Zheng Tianyu , Middleton Aurea , Kern Katelyn , Penoyer Daleen , Borsadia Rahul , Hunley Charles , Abomoelak Bassam , Mehta Vijay , Irastorza Laura , Mehta Devendra I. , Huo Qun
Published: December 2021

Upon infection with SARS-CoV-2, the virus that causes COVID-19, most people will develop no or mild symptoms. However, a small percentage of the population will become severely ill, and some will succumb to death. The clinical severity of COVID-19 has a close connection to the dysregulation of the patient’s immune functions. We previously developed a simple, nanoparticle-enabled blood test that can determine the humoral immune status in animals. In this study, we applied this new test to analyze the immune function in relation to disease severity in COVID-19 patients. From the testing of 153 COVID-19 patient samples and 142 negative controls, we detected a drastic decrease of humoral immunity in COVID-19 patients who developed moderate to severe symptoms, but not in patients with no or mild symptoms. The new test may be potentially used to monitor the immunity change and predict the clinical risk of patients with COVID-19.
Resistance training induces similar adaptations of upper and lower-body muscles between sexes
Authors: Kojić Filip , Mandić Danimir , Ilić Vladimir
Published: December 2021

The purpose of the study was to compare sex adaptations in hypertrophy, strength and contractile properties of upper and lower-body muscles induced by resistance training (RT). Eighteen RT untrained male (MG) and female (FG) students (aged 24.1 ± 1.7 years, height: 1.75 ± 0.08 m, weight: 70.4 ± 12.3 kg) undervent 7 weeks of biceps curl and squat training (2 days/week, 60–70% repetition maximum, 3–4 sets, 120 s rest intervals, reps until muscular failure). At baseline and final measurement, thickness and cross-section area, one-repetition maximum and tensiomyography parameters (contraction time − Tc and radial displacement − Dm) of elbow flexors (biceps brachii) and knee extensors (4 quadriceps muscles) were evaluated. Although MG tends to display greater absolute strength gains for upper- (p = 0.055) and lower-body (p = 0.098), for relative changes ANCOVA revealed no sex-specific differences for either of the tested variables. Significant hypertrophy was observed for all tested muscles, except for vastus intermedius in FG (p = 0.076). The Dm significantly decreased for biceps brachii (MG by 12%, p < 0.01 and FG by 13.1%, p < 0.01) and rectus femoris (MG by19.2%, p < 0.01 and FG by 12.3%, p < 0.05), while Tc values remain unchanged. These results indicate that initial morphological, functional and contractile alterations following RT are similar for males and females, and that there are no specific sex adaptations either for the upper- or lower-body muscles. The study was registered with ClinicalTrials.gov (NCT04845295).
Effects of process factors on performances of liquid membrane-based transfer of indole-3-acetic acid
Authors: Diaconu Ioana , Pârvulescu Oana Cristina , Topală Sorina Laura , Dobre Tănase
Published: December 2021

The paper has aimed at studying the transfer of indole 3-acetic acid (IAA) from a feed aqueous solution to a stripping aqueous solution of NaOH using a chloroform bulk liquid membrane and trioctylamine (TOA) as a ligand (L). Initial molar concentrations of IAA in the feed phase, cIAA,F0 (10–4–10–3 kmol/m3), of TOA in the membrane phase, cL,M0 (10–2 and 10–1 kmol/m3), and of NaOH in the stripping phase, cNaOH,S0 (10–2 and 1 kmol/m3), were selected as process factors. Their effects on the final values of IAA concentration in the feed phase (cIAA,Ff) and stripping solution (cIAA,Sf), extraction efficiency (EF), distribution coefficient (KD), and recovery efficiency (ER) were quantified using multiple regression equations. Regression coefficients were determined from experimental data, i.e., cIAA,Ff,ex = 0.02–1 × 10–4 kmol/m3, cIAA,Sf,ex = 0.22–2.58 × 10–3 kmol/m3, EF,ex = 90.0–97.9%, KD,ex = 9.0–46.6, and ER,ex = 66.5–94.2%. It was found that cIAA,F0 had the most significant positive effect on cIAA,Ff and cIAA,Sf, whereas cNaOH,S0 had a major positive effect on EF, KD, and ER. A deterministic model based on mass transfer of IAA was developed and its parameters, i.e., mass transfer coefficient of IAA-L complex in the liquid membrane (0.82–11.5 × 10–7 m/s) and extraction constant (1033.9–1779.7 m3/kmol), were regressed from experimental data. The effect of cL,M0 on both parameters was significant.
Application of droplet digital polymerase chain reaction of plasma methylated septin 9 on detection and early monitoring of colorectal cancer
Authors: Ma Zhi Yao , Chan Cherry Sze Yan , Lau Kam Shing , Ng Lui , Cheng Yuen Yee , Leung Wai K.
Published: December 2021

Methylated septin 9 (SEPT9) has been approved for non-invasive screening of colorectal cancer (CRC), but data on monitoring of CRC is sparse. Droplet digital polymerase chain reaction (ddPCR), with higher detection precision and simpler quantification than conventional PCR, has not been applied in SEPT9 detection. We explored the role of SEPT9 ddPCR for CRC detection and to measure serial SEPT9 levels in blood samples of CRC patients before and 3-month after surgery. SEPT9 methylated ratio, methylated abundance, and CEA levels were all higher in CRC patients than normal controls (all P < 0.05). The area under the curve (AUC) for methylated ratio and abundance to detect CRC was 0.707 and 0.710, respectively. There was an increasing trend for SEPT9 methylated abundance from proximal to distal cancers (P = 0.017). At 3-month after surgery, both methylated abundance and ratio decreased (P = 0.005 and 0.053, respectively), especially methylated abundance in stage III and distal cancer (both P < 0.01). We have developed a ddPCR platform for the quantitative detection of plasma SEPT9 in CRC patients. SEPT9 methylated abundance had an early post-operative decline, which may be useful in monitoring of treatment response.
Pilot imaging study of o-BMVC foci for discrimination of indeterminate cytology in diagnosing fine-needle aspiration of thyroid nodules
Authors: Tseng Ting-Yuan , Shih Shyang-Rong , Wang Cheng-Ping , Lin Shang-Jyun , Jan I.-Shiow , Wang Chiung-Lin , Liu Shin-Ya , Chang Cheng-Chung , Lou Pei-Jen , Chang Ta-Chau
Published: December 2021

Fluorescence lifetime imaging microscopy of a fluorescence probe, 3,6-bis(1-methyl-2-vinylpyridinium) carbazole diiodide (o-BMVC), provides an objective method for preoperative diagnosis of fine-needle aspiration (FNA) of thyroid nodules. The key of this o-BMVC test of FNA smears is the measurement of the digital number of o-BMVC foci in the nucleus. Thus, there are three categories classified in the o-BMVC test, which are nondiagnostic for unsatisfactory samples, benign for less numbers of o-BMVC foci, and malignant for more numbers of o-BMVC foci. The discrimination of indeterminate (including atypia, follicular neoplasm, suspicious) cytology into benign or malignant cases can reduce diagnostic uncertainty and benefit clinical decision making. This pilot study strongly suggests that the o-BMVC test is an invaluable method for diagnosing FNA samples. Particularly, the combination of FNA cytology and the o-BMVC test holds great promise to improve the efficacy of diagnosis and reduce the healthcare costs.
Peptides derived from gp43, the most antigenic protein from Paracoccidioides brasiliensis, form amyloid fibrils in vitro: implications for vaccine development
Authors: Cardim-Pires Thyago R. , Sant’Anna Ricardo , Foguel Debora
Published: December 2021

Fungal infection is an important health problem in Latin America, and in Brazil in particular. Paracoccidioides (mainly P. brasiliensis and P. lutzii) is responsible for paracoccidioidomycosis, a disease that affects mainly the lungs. The glycoprotein gp43 is involved in fungi adhesion to epithelial cells, which makes this protein an interesting target of study. A specific stretch of 15 amino acids that spans the region 181–195 (named P10) of gp43 is an important epitope of gp43 that is being envisioned as a vaccine candidate. Here we show that synthetic P10 forms typical amyloid aggregates in solution in very short times, a property that could hamper vaccine development. Seeds obtained by fragmentation of P10 fibrils were able to induce the aggregation of P4, but not P23, two other peptides derived from gp43. In silico analysis revealed several regions within the P10 sequence that can form amyloid with steric zipper architecture. Besides, in-silico proteolysis studies with gp43 revealed that aggregation-prone, P10-like peptides could be generated by several proteases, which suggests that P10 could be formed under physiological conditions. Considering our data in the context of a potential vaccine development, we redesigned the sequence of P10, maintaining the antigenic region (HTLAIR), but drastically reducing its aggregation propensity.
Equivalent inductance model for the design analysis of electrodynamic suspension coils for hyperloop
Authors: Lim Jungyoul , Lee Chang-Young , Oh Ye Jun , Jo Jeong-Min , Lee Jin-Ho , Lee Kwan-Sup , Choi Suyong
Published: December 2021

Hyperloop is a new concept of ground transportation. In Hyperloop, travelling occurs in near-vacuum tubes under 0.001 atm at a subsonic speed of up to 1200 km/h. During acceleration to and driving at a subsonic speed, magnetic levitation is employed. Thus far, various levitation technologies in existing high-speed maglev trains have been considered. Among those technologies, superconducting (SC) electrodynamic suspension (EDS) is a highly effective levitation system for Hyperloop owing to its advantages of a large levitation gap, levitation stability, and control being unnecessary. However, analyzing an EDS system requires the electromagnetic transient analysis of complex three-dimensional (3D) features, and its computational load generally limits the use of numerical methods, such as the 3D finite element method (FEM) or dynamic circuit theory. In this study, a novel model that can rapidly and accurately calculate the frequency-dependent equivalent inductance was developed. The developed model was then applied to design an EDS system using the decoupled resistance-inductance equations of levitation coils. Next, levitation coils of SC-EDS were designed and analyzed for use in Hyperloop. The obtained results were compared with the FEM results to validate the developed model. In addition, the model was experimentally validated by measuring currents induced by moving pods.
A phenomenological analysis of the experience of taking medication to prevent a further heart attack
Authors: Piekarz Hannah , Langran Catherine , Donyai Parastou
Published: December 2021

Following an acute myocardial infarction, patients are prescribed a regime of cardio-protective medication to prevent recurrent cardiovascular events and mortality. Adherence to medication is poor in this patient group, and not fully understood. Current interventions have made limited improvements but are based upon presumed principles. To describe the phenomenon of medicine-taking for an individual taking medication for secondary prevention for an AMI, Interpretative Phenomenological Analysis was used to analyse transcripts of semi-structured interviews with participants. Themes were generated for each participant, then summarized across participants. Five key themes were produced; the participants needed to compare themselves to others, showed that knowledge of their medicines was important to them, discussed how the future was an unknown entity for them, had assimilated their medicines into their lives, and expressed how an upset to their routine reduced their ability to take medication. Participants described complex factors and personal adaptations to taking their medication. This suggests that a patient-centred approach is appropriate for adherence work, and these themes could inform clinical practice to better support patients in their medicine adherence.