bluuebunny/crossref_metadata_2025 huggingface dataset:
Unexpected species diversity in electric eels with a description of the strongest living bioelectricity generator
Authors: de Santana C. David , Crampton William G. R. , Dillman Casey B. , Frederico Renata G. , Sabaj Mark H. , Covain Raphaël , Ready Jonathan , Zuanon Jansen , de Oliveira Renildo R. , Mendes-Júnior Raimundo N. , Bastos Douglas A. , Teixeira Tulio F. , Mol Jan , Ohara Willian , Castro Natália Castro e , Peixoto Luiz A. , Nagamachi Cleusa , Sousa Leandro , Montag Luciano F. A. , Ribeiro Frank , Waddell Joseph C. , Piorsky Nivaldo M. , Vari Richard P. , Wosiacki Wolmar B.
Published: September 2019

Is there only one electric eel species? For two and a half centuries since its description by Linnaeus, Electrophorus electricus has captivated humankind by its capacity to generate strong electric discharges. Despite the importance of Electrophorus in multiple fields of science, the possibility of additional species-level diversity in the genus, which could also reveal a hidden variety of substances and bioelectrogenic functions, has hitherto not been explored. Here, based on overwhelming patterns of genetic, morphological, and ecological data, we reject the hypothesis of a single species broadly distributed throughout Greater Amazonia. Our analyses readily identify three major lineages that diverged during the Miocene and Pliocene—two of which warrant recognition as new species. For one of the new species, we recorded a discharge of 860 V, well above 650 V previously cited for Electrophorus, making it the strongest living bioelectricity generator.
RuvC uses dynamic probing of the Holliday junction to achieve sequence specificity and efficient resolution
Authors: Górecka Karolina Maria , Krepl Miroslav , Szlachcic Aleksandra , Poznański Jarosław , Šponer Jiří , Nowotny Marcin
Published: September 2019

Holliday junctions (HJs) are four-way DNA structures that occur in DNA repair by homologous recombination. Specialized nucleases, termed resolvases, remove (i.e., resolve) HJs. The bacterial protein RuvC is a canonical resolvase that introduces two symmetric cuts into the HJ. For complete resolution of the HJ, the two cuts need to be tightly coordinated. They are also specific for cognate DNA sequences. Using a combination of structural biology, biochemistry, and a computational approach, here we show that correct positioning of the substrate for cleavage requires conformational changes within the bound DNA. These changes involve rare high-energy states with protein-assisted base flipping that are readily accessible for the cognate DNA sequence but not for non-cognate sequences. These conformational changes and the relief of protein-induced structural tension of the DNA facilitate coordination between the two cuts. The unique DNA cleavage mechanism of RuvC demonstrates the importance of high-energy conformational states in nucleic acid readouts.
Surpassing the 10% efficiency milestone for 1-cm2 all-polymer solar cells
Authors: Fan Baobing , Zhong Wenkai , Ying Lei , Zhang Difei , Li Meijing , Lin Yanrui , Xia Ruoxi , Liu Feng , Yip Hin-Lap , Li Ning , Ma Yuguang , Brabec Christoph J. , Huang Fei , Cao Yong
Published: September 2019

Naphthalenediimide-based n-type polymeric semiconductors are extensively used for constructing high-performance all-polymer solar cells (all-PSCs). For such all-polymer systems, charge recombination can be reduced by using thinner active layers, yet suffering insufficient near-infrared light harvesting from the polymeric acceptor. Conversely, increasing the layer thickness overcomes the light harvesting issue, but at the cost of severe charge recombination effects. Here we demonstrate that to manage light propagation within all-PSCs, a thick bulk-heterojunction film of approximately 350 nm is needed to effectively enhance photo-harvesting in the near-infrared region. To overcome the severe charge recombination in such a thick film, a non-halogenic additive is used to induce a well-ordered micro-structure that inherently suppresses recombination loss. The combined strategies of light management and delicate morphology optimization lead to a promising efficiency over 10% for thick-film all-PSCs with active area of 1 cm2, showing great promise for future large-scale production and application of all-PSCs.
Computational study of paroxetine-like inhibitors reveals new molecular insight to inhibit GRK2 with selectivity over ROCK1
Authors: Keretsu Seketoulie , Bhujbal Swapnil P. , Joo Cho Seung
Published: September 2019

The G-protein coupled receptor kinase 2 (GRK2) regulates the desensitization of beta-adrenergic receptors (β-AR), and its overexpression has been implicated in heart failure. Hence, the inhibition of GRK2 is considered to be an important drug target for the treatment of heart failure. Due to the high sequence similarity of GRK2 with the A, G, and C family (AGC family) of kinases, the inhibition of GRK2 also leads to the inhibition of AGC kinases such as Rho-associated coiled-coil kinase 1 (ROCK1). Therefore, unraveling the mechanisms to selectively inhibit GRK2 poses an important challenge. We have performed molecular docking, three dimensional quantitative structure activity relationship (3D-QSAR), molecular dynamics (MD) simulation, and free energy calculations techniques on a series of 53 paroxetine-like compounds to understand the structural properties desirable for enhancing the inhibitory activity for GRK2 with selectivity over ROCK1. The formation of stable hydrogen bond interactions with the residues Phe202 and Lys220 of GRK2 seems to be important for selective inhibition of GRK2. Electropositive substituents at the piperidine ring and electronegative substituents near the amide linker between the benzene ring and pyrazole ring showed a higher inhibitory preference for GRK2 over ROCK1. This study may be used in designing more potent and selective GRK2 inhibitors for therapeutic intervention of heart failure.
A core-shell molybdenum nanoparticles entrapped f-MWCNTs hybrid nanostructured material based non-enzymatic biosensor for electrochemical detection of dopamine neurotransmitter in biological samples
Authors: Keerthi Murugan , Boopathy Gopal , Chen Shen-Ming , Chen Tse-Wei , Lou Bih-Show
Published: September 2019

Dopamine (DA) is a critical neurotransmitter and has been known to be liable for several neurological diseases. Hence, its sensitive and selective detection is essential for the early diagnosis of diseases related to abnormal levels of DA. In this study, we reported novel molybdenum nanoparticles self-supported functionalized multiwalled carbon nanotubes (Mo NPs@f-MWCNTs) based core-shell hybrid nanomaterial with an average diameter of 40–45 nm was found to be the best for electrochemical DA detection. The Mo NPs@f-MWCNTs hybrid material possesses tremendous superiority in the DA sensing is mainly due to the large surface area and numerous electroactive sites. The morphological and structural characteristics of the as-synthesized hybrid nanomaterial were examined by XRD, Raman, FE-SEM, HR-TEM, EDX. The electrochemical characteristics and catalytic behavior of the as-prepared Mo NPs@f-MWCNTs modified screen-printed carbon electrode for the determination of DA were systematically investigated via electrochemical impedance spectroscopy, cyclic voltammetry, and amperometry. The results demonstrate that the developed DA biosensor exhibit a low detection limit of 1.26 nM, excellent linear response of 0.01 µM to 1609 µM with good sensitivity of 4.925 µA µM−1 cm−2. We proposed outstanding appreciable stability sensor was expressed to the real-time detection of DA in the real sample analysis of rat brain, human blood serum, and DA hydrochloride injection.
ePath: an online database towards comprehensive essential gene annotation for prokaryotes
Authors: Kong Xiangzhen , Zhu Bin , Stone Victoria N. , Ge Xiuchun , El-Rami Fadi E. , Donghai Huangfu , Xu Ping
Published: September 2019

Experimental techniques for identification of essential genes (EGs) in prokaryotes are usually expensive, time-consuming and sometimes unrealistic. Emergingin silicomethods provide alternative methods for EG prediction, but often possess limitations including heavy computational requirements and lack of biological explanation. Here we propose a new computational algorithm for EG prediction in prokaryotes with an online database (ePath) for quick access to the EG prediction results of over 4,000 prokaryotes (https://www.pubapps.vcu.edu/epath/). In ePath, gene essentiality is linked to biological functions annotated by KEGG Ortholog (KO). Two new scoring systems, namely, E_score and P_score, are proposed for each KO as the EG evaluation criteria. E_score represents appearance and essentiality of a given KO in existing experimental results of gene essentiality, while P_score denotes gene essentiality based on the principle that a gene is essential if it plays a role in genetic information processing, cell envelope maintenance or energy production. The new EG prediction algorithm shows prediction accuracy ranging from 75% to 91% based on validation from five new experimental studies on EG identification. Our overall goal with ePath is to provide a comprehensive and reliable reference for gene essentiality annotation, facilitating the study of those prokaryotes without experimentally derived gene essentiality information.
Nucleation dynamics of single crystal WS2 from droplet precursors uncovered by in-situ monitoring
Authors: Li Chao , Kameyama Tomoya , Takahashi Tomoyuki , Kaneko Toshiro , Kato Toshiaki
Published: September 2019

Transition metal dichalcogenides (TMDs) attract intence attention due to its unique optoelectrical features. Recent progress in production stage of TMD enables us to synthesis uniform and large area TMD with mono layer thickness. Elucidation of growth mechanism is a challenge to improve the crystallinity of TMD, which is regargeded as a next crutial subject in the production stage. Here we report novel diffusion and nucleation dynamics during tungsten disulphide (WS2) growth. The diffusion length (Ld) of the precursors have been measured with unique nucleation control methods. It was revealed that the Ld reaches up to ~750 μm. This ultra-long diffusion can be attributed to precursor droplets observed during in-situ monitoring of WS2 growth. The integrated synthesis of >35,000 single crystals and monolayer WS2 was achieved at the wafer scale based on this model. Our findings are highly significant for both the fundamental study of droplet-mediated crystal growth and the industrial application of integrated single-crystal TMDs.
Glycine administration attenuates progression of dystrophic pathology in prednisolone-treated dystrophin/utrophin null mice
Authors: Ham Daniel J. , Gardner Anastasia , Kennedy Tahnee L. , Trieu Jennifer , Naim Timur , Chee Annabel , Alves Francesca M. , Caldow Marissa K. , Lynch Gordon S. , Koopman René
Published: September 2019

Duchenne muscular dystrophy (DMD) is an X-linked genetic disease characterized by progressive muscle wasting and weakness and premature death. Glucocorticoids (e.g. prednisolone) remain the only drugs with a favorable impact on DMD patients, but not without side effects. We have demonstrated that glycine preserves muscle in various wasting models. Since glycine effectively suppresses the activity of pro-inflammatory macrophages, we investigated the potential of glycine treatment to ameliorate the dystrophic pathology. Dystrophic mdx and dystrophin-utrophin null (dko) mice were treated with glycine or L-alanine (amino acid control) for up to 15 weeks and voluntary running distance (a quality of life marker and strong correlate of lifespan in dko mice) and muscle morphology were assessed. Glycine increased voluntary running distance in mdx mice by 90% (P < 0.05) after 2 weeks and by 60% (P < 0.01) in dko mice co-treated with prednisolone over an 8 week treatment period. Glycine treatment attenuated fibrotic deposition in the diaphragm by 28% (P < 0.05) after 10 weeks in mdx mice and by 22% (P < 0.02) after 14 weeks in dko mice. Glycine treatment augmented the prednisolone-induced reduction in fibrosis in diaphragm muscles of dko mice (23%, P < 0.05) after 8 weeks. Our findings provide strong evidence that glycine supplementation may be a safe, simple and effective adjuvant for improving the efficacy of prednisolone treatment and improving the quality of life for DMD patients.
Molecular form and concentration of serum α2-macroglobulin in diabetes
Authors: Yoshino Sonomi , Fujimoto Kazumi , Takada Tesshu , Kawamura Sayuki , Ogawa Junro , Kamata Yuji , Kodera Yoshio , Shichiri Masayoshi
Published: September 2019

α2-Macroglobulin is a highly abundant serum protein involved in the development of atherosclerosis and cardiac hypertrophy. However, its circulating molecular form and exact concentrations in human health/diseases are not known. Blue native-polyacrylamide gel electrophoresis of human serum was used to confirm the native conformation of α2-macroglobulin. We created an enzyme-linked immunosorbent assay suitable for quantifying its circulating molecular form and undertook a cross-sectional study to measure its serum levels in 248 patients with diabetes mellitus and 59 healthy volunteers. The predominant circulating molecular form of α2-macroglobulin was the tetramer, whereas its dimer was detectable in patients with high serum levels of α2-macroglobulin. The serum α2-macroglobulin concentration was not associated with glycated hemoglobin or any other glycemic variable as evaluated from 48-h continuous glucose monitoring, but showed close correlation with left ventricular posterior wall thickness, carotid artery intima-media thickness, urinary albumin:creatinine ratio (ACR) and brachial–ankle pulse wave velocity (baPWV). Multivariate analysis revealed only the ACR and baPWV to be independent variables influencing serum levels of α2-macroglobulin. Thus, an increased ACR and baPWV are associated with higher serum concentrations of α2-macroglobulin, and the latter may contribute to the mechanism by which albuminuria increases the risk of developing cardiovascular diseases.
Yellow fever in Brazil threatens successful recovery of endangered golden lion tamarins
Authors: Dietz James M. , Hankerson Sarah J. , Alexandre Brenda Rocha , Henry Malinda D. , Martins Andréia F. , Ferraz Luís Paulo , Ruiz-Miranda Carlos R.
Published: September 2019

The golden lion tamarin is an endangered primate endemic to Brazil’s Atlantic Forest. Centuries of deforestation reduced numbers to a few hundred individuals in isolated forest fragments 80 km from Rio de Janeiro city. Intensive conservation action including reintroduction of zoo-born tamarins into forest fragments 1984–2000, increased numbers to about 3,700 in 2014. Beginning in November 2016, southeastern Brazil experienced the most severe yellow fever epidemic/epizootic in the country in 80 years. In May 2018, we documented the first death of a golden lion tamarin due to yellow fever. We re-evaluated population sizes and compared them to results of a census completed in 2014. Tamarin numbers declined 32%, with ca. 2,516 individuals remainingin situ. Tamarin losses were significantly greater in forest fragments that were larger, had less forest edge and had better forest connectivity, factors that may favor the mosquito vectors of yellow fever. The future of golden lion tamarins depends on the extent of additional mortality, whether some tamarins survive the disease and acquire immunity, and the potential development of a vaccine to protect the species against yellow fever.
Mathematical modeling for bioprocess optimization of a protein drug, uricase, production by Aspergillus welwitschiae strain 1–4
Authors: El-Naggar Noura El-Ahmady , Haroun S. A. , El-Weshy Eman M. , Metwally E. A. , Sherief A. A.
Published: September 2019

Microbial uricase is effective protein drug used to treat hyperuricemia and its complications, including chronic gout, also in prophylaxis and treatment of tumor lysis and organ transplants hyperuricemia. Uricase is commonly used as diagnostic reagent in clinical analysis for quantification of uric acid in blood and other biological fluids. Also, it can be used as an additive in formulations of hair coloring agents. A newly isolated strain, Aspergillus sp. 1–4, was able to produce extracellular uricase on a medium containing uric acid as inducer. Phylogenetic analysis based on ITS region sequence analysis and phenotypic characteristics showed that Aspergillus sp. strain 1–4 is closely related to Aspergillus welwitschiae and its nucleotide sequence was deposited in the GenBank database and assigned sequence accession number MG323529. Statistical screening using Plackett-Burman design with 20 runs was applied to screen fifteen factors for their significance on uricase production by Aspergillus welwitschiae. Results of statistical analysis indicated that incubation time has the most significant positive effect on uricase production followed by yeast extract and inoculum size with the highest effect values of 13.48, 5.26 and 4.75; respectively. The interaction effects and optimal levels of these factors were evaluated using central composite design. The maximum uricase production was achieved at incubation time (5 days), yeast extract (2 g/L) and inoculum size (4 mL/50 mL medium) are the optimum levels for maximum uricase production (60.03 U/mL). After optimization, uricase production increased by 3.02-folds as compared with that obtained from the unoptimized medium (19.87 U/mL).
Analog simulator of integro-differential equations with classical memristors
Authors: Barrios G. Alvarado , Retamal J. C. , Solano E. , Sanz M.
Published: September 2019

An analog computer makes use of continuously changeable quantities of a system, such as its electrical, mechanical, or hydraulic properties, to solve a given problem. While these devices are usually computationally more powerful than their digital counterparts, they suffer from analog noise which does not allow for error control. We will focus on analog computers based on active electrical networks comprised of resistors, capacitors, and operational amplifiers which are capable of simulating any linear ordinary differential equation. However, the class of nonlinear dynamics they can solve is limited. In this work, by adding memristors to the electrical network, we show that the analog computer can simulate a large variety of linear and nonlinear integro-differential equations by carefully choosing the conductance and the dynamics of the memristor state variable. We study the performance of these analog computers by simulating integro-differential models related to fluid dynamics, nonlinear Volterra equations for population growth, and quantum models describing non-Markovian memory effects, among others. Finally, we perform stability tests by considering imperfect analog components, obtaining robust solutions with up to 13% relative error for relevant timescales.
Damped resonance for broadband acoustic absorption in one-port and two-port systems
Authors: Lee Taehwa , Nomura Tsuyoshi , Iizuka Hideo
Published: September 2019

We demonstrate broadband perfect acoustic absorption by damped resonances through inclusion of lossy porous media. By minimally placing the lossy materials around the necks of single-resonance Helmholtz resonators, where acoustic energy is concentrated, we show an increase in absorption bandwidths (>100% of the resonance frequency). Using the damped resonance, we demonstrate three types of broadband acoustic absorbers in one-port and two-port systems: broadband absorbers (one-port), broadband sparse absorbers (two-port), and broadband duct absorbers (two-port). Our approach for broadband absorption allows to minimize the number of resonances for compact absorbers, while it is beneficial for practical applications owing to the minimum use of porous materials.
Delocalisation of Majorana quasiparticles in plaquette–nanowire hybrid system
Authors: Kobiałka Aksel , Domański Tadeusz , Ptok Andrzej
Published: September 2019

Interplay between superconductivity, spin-orbit coupling and magnetic field can lead to realisation of the topologically non–trivial states which in finite one dimensional nanowires are manifested by emergence of a pair of zero-energy Majorana bound states. On the other hand, in two dimensional systems the chiral edge states can appear. We investigate novel properties of the bound states in a system of mixed dimensionality, composed of one-dimensional nanowire connected with two-dimensional plaquette. We study this system, assuming either its part or the entire structure to be in topologically non–trivial superconducting state. Our results show delocalisation of the Majorana modes, upon leaking from the nanowire to the plaquette with some tendency towards its corners.
Platelet-leukocyte aggregate is associated with adverse events after surgical intervention for rheumatic heart disease
Authors: Liu Chaonan , Yang Yang , Du Lei , Chen Si , Zhang Jie , Zhang Chongwei , Zhou Jing
Published: September 2019

Platelet-leukocyte aggregate (PLA) is implicated in the etiology of both vascular lesions and cardiovascular events. This prospective cohort study aimed to examine the prognostic value of PLA for major adverse cardiac and cerebrovascular events (MACCE) and perioperative adverse events (AEs) in patients with rheumatic heart disease undergoing surgical intervention by Cox proportional hazard regression and logistic regression. A total of 244 patients were included, of whom 7 were lost to follow-up. Among the analyzed 237 subjects who completed 3-year follow-up, 30 experienced MACCE and 38 experienced perioperative AEs. Preoperative PLA was higher in subjects who developed MACCE (13.32%) than in those who did not (8.69%, p = 0.040). In multivariate regression, elevated PLA was associated with increased MACCE (hazard ratio 1.51 for each quartile, 95% CI 1.07–2.13; p = 0.020), and perioperative AEs (odds ratio 1.61, 95% CI 1.14–2.26; p = 0.007). The optimal PLA cut-off for predicting MACCE was 6.8%. Subjects with PLA > 6.8% had a higher prevalence of MACCE (17.1% vs. 5.5%, p = 0.009) and perioperative AEs (19.9% vs. 8.6%, p = 0.018). Kaplan-Meier analysis showed shorter MACCE-free survival in patients with PLA > 6.8% (p = 0.007, log rank). Elevated preoperative PLA is associated with increased MACCE and perioperative AEs in patients with rheumatic valve disease undergoing surgical intervention.
Genomic and developmental characterisation of a novel bunyavirus infecting the crustacean Carcinus maenas
Authors: Bojko Jamie , Subramaniam Kuttichantran , Waltzek Thomas B. , Stentiford Grant D. , Behringer Donald C.
Published: September 2019

Carcinus maenas is in the top 100 globally invasive species and harbours a wide diversity of pathogens, including viruses. We provide a detailed description for a novel bunyavirus (Carcinus maenas Portunibunyavirus 1) infecting C. maenas from its native range in the Faroe Islands. The virus genome is tripartite, including large (L) (6766 bp), medium (M) (3244 bp) and small (S) (1608 bp) negative sense, single-stranded RNA segments. Individual genomic segments are flanked by 4 bp regions of similarity (CCUG). The segments encode an RNA-dependent RNA-polymerase, glycoprotein, non-structural protein with a Zinc-Finger domain and a nucleoprotein. Most show highest identity to the ‘Wenling Crustacean Virus 9’ from an unidentified crustacean host. Phylogenomics of crustacean-infecting bunyaviruses place them across multiple bunyavirus families. We discuss the diversity of crustacean bunyaviruses and provide an overview of how these viruses may affect the health and survival of crustacean hosts, including those inhabiting niches outside of their native range.
Novel Method for Rapid Assessment of Cognitive Impairment Using High-Performance Eye-Tracking Technology
Authors: Oyama Akane , Takeda Shuko , Ito Yuki , Nakajima Tsuneo , Takami Yoichi , Takeya Yasushi , Yamamoto Koichi , Sugimoto Ken , Shimizu Hideo , Shimamura Munehisa , Katayama Taiichi , Rakugi Hiromi , Morishita Ryuichi
Published: September 2019

A rapid increase in the number of patients with dementia has emerged as a global health challenge. Accumulating evidence suggests that early diagnosis and timely intervention can delay cognitive decline. The diagnosis of dementia is commonly performed using neuropsychological tests, such as the Mini-Mental State Examination (MMSE), administered by trained examiners. While these traditional neuropsychological tests are valid and reliable, they are neither simple nor sufficiently short as routine screening tools for dementia. Here, we developed a brief cognitive assessment utilizing an eye-tracking technology. The subject views a series of short (178 s) task movies and pictures displayed on a monitor while their gaze points are recorded by the eye-tracking device, and the cognitive scores are determined from the gaze plots data. The cognitive scores were measured by both an eye tracking-based assessment and neuropsychological tests in 80 participants, including 27 cognitively healthy controls (HC), 26 patients with mild cognitive impairment (MCI), and 27 patients with dementia. The eye tracking-based cognitive scores correlated well with the scores from the neuropsychological tests, and they showed a good diagnostic performance in detecting patients with MCI and dementia. Rapid cognitive assessment using eye-tracking technology can enable quantitative scoring and the sensitive detection of cognitive impairment.
Heteroplasmy concordance between mitochondrial DNA and RNA
Authors: Zhang Ruoyu , Nakahira Kiichi , Choi Augustine M. K. , Gu Zhenglong
Published: September 2019

Mitochondrial DNA (mtDNA) heteroplasmies are associated with various diseases but the transmission of heteroplasmy from mtDNA to mitochondrial RNA (mtRNA) remains unclear. We compared heteroplasmies in mtRNA from 446 human B-lymphoblastoid cell lines to their corresponding mtDNA using deep sequencing data from two independent studies. We observed 2786 heteroplasmies presenting in both DNA and RNA at 1% frequency cutoff. Among them, the frequencies of 2427 (87.1%) heteroplasmies were highly consistent (less than 5% frequency difference) between DNA and RNA. To validate these frequency consistencies, we isolated DNA and RNA simultaneously from GM12282 cell line used in those two sequencing studies, and resequenced its heteroplasmy sites. Interestingly, we also observed the rapid changes of heteroplasmy frequencies during 4 weeks of the cell culture: the frequencies at Day 14 increased by >25% than those at Day 0. However, the heteroplasmy frequencies from the same time point were highly consistent. In summary, our analysis on public data together within vitrostudy indicates that the heteroplasmies in DNA can be transcribed into RNA with high fidelity. Meanwhile, the observed rapid-changing heteroplasmy frequency can potentially disturb cell functions, which could be an overlooked confounding factor in cell line related studies.
Quantitative assessment of myelination patterns in preterm neonates using T2-weighted MRI
Authors: Wang Siying , Ledig Christian , Hajnal Joseph V. , Counsell Serena J. , Schnabel Julia A. , Deprez Maria
Published: September 2019

Myelination is considered to be an important developmental process during human brain maturation and closely correlated with gestational age. Quantitative assessment of the myelination status requires dedicated imaging, but the conventional T2-weighted scans routinely acquired during clinical imaging of neonates carry signatures that are thought to be associated with myelination. In this work, we develop a quatitative marker of progressing myelination for assessment preterm neonatal brain maturation based on novel automatic segmentation method for myelin-like signals on T2-weighted magnetic resonance images. Firstly we define a segmentation protocol for myelin-like signals. We then develop an expectation-maximization framework to obtain the automatic segmentations of myelin-like signals with explicit class for partial volume voxels whose locations are configured in relation to the composing pure tissues via second-order Markov random fields. The proposed segmentation achieves high Dice overlaps of 0.83 with manual annotations. The automatic segmentations are then used to track volumes of myelinated tissues in the regions of the central brain structures and brainstem. Finally, we construct a spatio-temporal growth models for myelin-like signals, which allows us to predict gestational age at scan in preterm infants with root mean squared error 1.41 weeks.
Genetic diversity, phylogenetic structure and development of core collections in Melilotus accessions from a Chinese gene bank
Authors: Zhang Hongxiang , Bai Rong , Wu Fan , Guo Wenli , Yan Zhuanzhuan , Yan Qi , Zhang Yufei , Ma Jinxing , Zhang Jiyu
Published: September 2019

Melilotus is an important forage legume, with high values as feed and medicine, and widely used as green manure, honey plant, and wildlife habitat enhancer. The genetic diversity, structure and subdivision of this forage crop remain unclear, and plant genetic resources are the basis of biodiversity and ecosystem diversity and have attracted increasing attention. In this study, the whole collection of 573 accessions from the National Gene Bank of Forage Germplasm (NGBFG, China) and 48 accessions from the National Plant Germplasm System (NPGS, USA) in genus Melilotus were measured with respect to five seed characters: seed length, width, width-to-length ratio, circumference and 100-seed weight. Shannon’ genetic diversity index (H’) and phenotypic differentiation (Pst) were calculated to better describe the genetic diversity. The ITS and matK sequences were used to construct phylogenetic trees and study the genetic relationships within genus Melilotu. Based on seed morphology and molecular marker data, we preliminarily developed core collections and the sampling rates of M. albus and M. officinalis were determined to be 15% and 25%, respectively. The results obtained here provide preliminary sorting and supplemental information for the Melilotus collections in NGBFG, China, and establish a reference for further genetic breeding and other related projects.
Omega-3 fatty acids decrease oxidative stress and inflammation in macrophages from patients with small abdominal aortic aneurysm
Authors: Meital Lara T. , Windsor Mark T. , Perissiou Maria , Schulze Karl , Magee Rebecca , Kuballa Anna , Golledge Jonathan , Bailey Tom G. , Askew Christopher D. , Russell Fraser D.
Published: September 2019

Abdominal aortic aneurysm (AAA) is associated with inflammation and oxidative stress, the latter of which contributes to activation of macrophages, a prominent cell type in AAA. Omega-3 polyunsaturated fatty acids (n-3 PUFAs) have been reported to limit oxidative stress in animal models of AAA. The aim of this study was to evaluate the effect of the n-3 PUFA docosahexaenoic acid (DHA) on antioxidant defence in macrophages from patients with AAA. Cells were obtained from men with small AAA (diameter 3.0–4.5 cm, 75 ± 6 yr, n = 19) and age- matched male controls (72 ± 5 yr, n = 41) and incubated with DHA for 1 h before exposure to 0.1 µg/mL lipopolysaccharide (LPS) for 24 h. DHA supplementation decreased the concentration of tumour necrosis factor-α (TNF-α; control, 42.1 ± 13.6 to 5.1 ± 2.1 pg/ml, p < 0.01; AAA, 25.2 ± 9.8 to 1.9 ± 0.9 pg/ml, p < 0.01) and interleukin-6 (IL-6; control, 44.9 ± 7.7 to 5.9 ± 2.0 pg/ml, p < 0.001; AAA, 24.3 ± 5.2 to 0.5 ± 0.3 pg/ml, p < 0.001) in macrophage supernatants. DHA increased glutathione peroxidase activity (control, 3.2 ± 0.3 to 4.1 ± 0.2 nmol/min/ml/μg protein, p = 0.004; AAA, 2.3 ± 0.5 to 3.4 ± 0.5 nmol/min/ml/μg protein, p = 0.008) and heme oxygenase-1 mRNA expression (control, 1.5-fold increase, p < 0.001). The improvements in macrophage oxidative stress status serve as a stimulus for further investigation of DHA in patients with AAA.
Highly c-axis orientated superconducting core and large critical current density in Ba0.6Na0.4Fe2As2 powder-in-tube tape
Authors: Imai S. , Itou S. , Ishida S. , Tsuchiya Y. , Iyo A. , Eisaki H. , Matsuzaki K. , Nishio T. , Yoshida Y.
Published: September 2019

Improvement of the critical current density (Jc) of superconducting wires/tapes is one of the key issues in the field of superconductivity applications. Here we report the fabrication of a silver-sheathed Ba1−xNaxFe2As2 (BaNa-122) superconducting tape by using a powder-in-tube technique and its superconducting properties, in particular transport Jc, as well as the tape-core texture. The optimally-doped BaNa-122 tape with Na concentration x = 0.4 exhibits the superconducting critical temperature (Tc) of 33.7 K and high transport Jc of 4 × 104 A/cm2 at 4.2 K in a magnetic field of 4 T. Patterns of x-ray diffraction for the superconducting core show that the degree of c-axis orientation is significantly enhanced through the tape fabrication process. The tendency of c-axis orientation is advantageous for achieving higher Jc, suggesting the high potential of BaNa-122 for superconducting wire/tape applications.
Aberrant Regulation of RAD51 Promotes Resistance of Neoadjuvant Endocrine Therapy in ER-positive Breast Cancer
Authors: Jia Yan , Song Yueshuai , Dong Guolei , Hao Chunfang , Zhao Weipeng , Li Shufen , Tong Zhongsheng
Published: September 2019

Breast cancer is one of the most common malignant cancers affecting females. Estrogen receptor (ER)-positive breast cancer is responsive to endocrine therapy. Although current therapies offer favorable prospects for improving survival, the development of resistance remains a severe problem. In this study, we explored the resistance mechanisms of ER-positive breast cancer to neoadjuvant endocrine therapy. Microarray data of GSE87411 contained 109 pairs of samples from Z1031 trial, including untreated samples and post-treated samples with neoadjuvant aromatase inhibitor (AI) therapy. The differentially expressed genes (DEGs) were obtained from two different comparisons: untreated samples versus post-treated samples with AIs, and post-treated samples sensitive versus resistant to AIs. Multiple bioinformatic methods were applied to evaluate biological function, protein-protein network and potential binding between target protein and aromatase inhibitor. Then, regulation of gene expression, DNA methylation and clinicopathological factors of breast cancer were further analyzed with TCGA data. From GSE87411 dataset, 30 overlapped DEGs were identified. Cell division was found to be the main function of overlapped DEGs by functional enrichment and gene ontology (GO) analysis. RAD51 recombinase (RAD51), a key protein of homologous recombination, was detected to interact with BReast CAncer genes 2 (BRCA2). Moreover, according to the docking simulation, RAD51 might potentially bind to AIs. Overexpressed RAD51 was associated with hypermethylation of BRCA2, resistance to AIs and poor overall survival of patients with ER-positive breast cancer. Furthermore, RAD51 was found to be a better indicator than MKI67 for predicting resistance in neoadjuvant setting. The results indicated that methylation of BRCA2 led to incomplete suppression on RAD51, which caused an increased expression of RAD51, subsequently AI-resistance and poor prognosis in ER-positive breast cancer. RAD51 could be a new candidate used as a predicative marker and therapeutic target in neoadjuvant endocrine treatment.
Generation of Broadband High-Purity Dual-Mode OAM Beams Using A Four-Feed Patch Antenna: Theory and Implementation
Authors: Huang Yuhan , Li Xiuping , Li Qingwen , Qi Zihang , Zhu Hua , Akram Zaid , Jiang Xing
Published: September 2019

A broadband four-feed circular patch antenna is demonstrated to generate high-purity dual-mode vortex beams carrying orbital angular momentum (OAM) for the first time. The electric field formula of the circularly polarized (CP) component is derived for analyzing radiation characteristics of different OAM modes, such as the CP property, phase and amplitude distributions. Theoretical calculation and numerical simulation results show that the four-feed patch antenna operating in the TMn1 mode can generate ±n OAM waves. A prototype of a four-feed circular TM21-mode patch antenna is fabricated and measured to verify the effectiveness of the theoretical analysis. The proposed antenna consists of a four-feed patch with an air-coupled parasitic patch and a four-way phase-shifting feeding network. Experimental results show that the proposed antenna can generate a left-hand CP OAM with mode l = +2 and a right-hand CP OAM with mode l = −2. The OAM beams are generated in a wide band from 5.50 to 6.50 GHz with a mode purity over 90%. The proposed method is very suitable for the generation of wideband, dual-mode and high-purity OAM beams in the microwave and millimeter wave bands.
Long-term stabilization of hydrogen peroxide by poly(vinyl alcohol) on paper-based analytical devices
Authors: Boonpoempoon Tuchpongpuch , Wonsawat Wanida , Kaneta Takashi
Published: September 2019

Stabilizing reagents that can be deposited onto paper is an important issue for researchers who depend on paper-based analytical devices (PADs), because long-term stability of the devices is essential in point-of-care testing. Here, we found that poly(vinyl alcohol) (PVA) would stabilize hydrogen peroxide placed on a paper substrate following exposure to air. Horseradish peroxidase was employed as a sample in colorimetric measurements of PADs after hydrogen peroxide and 3,3′,5,5′-tetramethylbenzidine were deposited as substrates in an enzymatic reaction. The addition of PVA to hydrogen peroxide significantly suppressed its degradation. Concentrations of PVA that ranged from 0.5 to 2%, increased the duration of the stability of hydrogen peroxide, and the results for a PVA concentration of 1% approximated those of 2% PVA. Storage of the PADs at 4 °C in a refrigerator extended the stability of the hydrogen peroxide containing 2% PVA by as much as 30 days. The stability of hydrogen peroxide without PVA was degraded after one day under room temperature.
Generative adversarial network based on chaotic time series
Authors: Naruse Makoto , Matsubara Takashi , Chauvet Nicolas , Kanno Kazutaka , Yang Tianyu , Uchida Atsushi
Published: September 2019

Generative adversarial networks (GANs) are becoming increasingly important in the artificial construction of natural images and related functionalities, wherein two types of networks called generators and discriminators evolve through adversarial mechanisms. Using deep convolutional neural networks and related techniques, high-resolution and highly realistic scenes, human faces, etc. have been generated. GANs generally require large amounts of genuine training data sets, as well as vast amounts of pseudorandom numbers. In this study, we utilized chaotic time series generated experimentally by semiconductor lasers for the latent variables of a GAN, whereby the inherent nature of chaos could be reflected or transformed into the generated output data. We show that the similarity in proximity, which describes the robustness of the generated images with respect to minute changes in the input latent variables, is enhanced, while the versatility overall is not severely degraded. Furthermore, we demonstrate that the surrogate chaos time series eliminates the signature of the generated images that is originally observed corresponding to the negative autocorrelation inherent in the chaos sequence. We also address the effects of utilizing chaotic time series to retrieve images from the trained generator.
Endemic diversity and distribution of the Iranian vascular flora across phytogeographical regions, biodiversity hotspots and areas of endemism
Authors: Noroozi Jalil , Talebi Amir , Doostmohammadi Moslem , Manafzadeh Sara , Asgarpour Zahra , Schneeweiss Gerald M.
Published: September 2019

Endemism is one of the most important concepts in biogeography and is of high relevance for conservation biology. Nevertheless, our understanding of patterns of endemism is still limited in many regions of high biodiversity. This is also the case for Iran, which is rich in biodiversity and endemism, but there is no up-to-date account of diversity and distribution of its endemic species. In this study, a comprehensive list of all endemic vascular plant species of Iran, their taxonomic composition and their geographical distribution are presented. To this end, a total of 2,597 (sub)endemic vascular plant species of Iran were documented and their distribution in three phytogeographical regions, two biodiversity hotspots and five areas of endemism were analysed. The Irano-Turanian phytogeographical region harbours 88% of the Iranian endemics, the majority of which are restricted to the Irano-Anatolian biodiversity hotspot (84%). Nearly three quarters of the endemic species are restricted to mountain ranges. The rate of endemism increases along an elevational gradient, causing the alpine zone to harbour a disproportionally high number of endemics. With increasing pastoralism, urbanization, road construction and ongoing climate change, the risk of biodiversity loss in the Iranian mountains is very high, and these habitats need to be more effectively protected.
Adipose cell size changes are associated with a drastic actin remodeling
Authors: Hansson Björn , Morén Björn , Fryklund Claes , Vliex Lars , Wasserstrom Sebastian , Albinsson Sebastian , Berger Karin , Stenkula Karin G.
Published: September 2019

Adipose tissue plays a major role in regulating whole-body insulin sensitivity and energy metabolism. To accommodate surplus energy, the tissue rapidly expands by increasing adipose cell size (hypertrophy) and cell number (hyperplasia). Previous studies have shown that enlarged, hypertrophic adipocytes are less responsive to insulin, and that adipocyte size could serve as a predictor for the development of type 2 diabetes. In the present study, we demonstrate that changes in adipocyte size correlate with a drastic remodeling of the actin cytoskeleton. Expansion of primary adipocytes following 2 weeks of high-fat diet (HFD)-feeding in C57BL6/J mice was associated with a drastic increase in filamentous (F)-actin as assessed by fluorescence microscopy, increased Rho-kinase activity, and changed expression of actin-regulating proteins, favoring actin polymerization. At the same time, increased cell size was associated with impaired insulin response, while the interaction between the cytoskeletal scaffolding protein IQGAP1 and insulin receptor substrate (IRS)-1 remained intact. Reversed feeding from HFD to chow restored cell size, insulin response, expression of actin-regulatory proteins and decreased the amount of F-actin filaments. Together, we report a drastic cytoskeletal remodeling during adipocyte expansion, a process which could contribute to deteriorating adipocyte function.
G-CSF and GM-CSF Modify Neutrophil Functions at Concentrations found in Cystic Fibrosis
Authors: Castellani Stefano , D’Oria Susanna , Diana Anna , Polizzi Angela Maria , Di Gioia Sante , Mariggiò Maria Addolorata , Guerra Lorenzo , Favia Maria , Vinella Angela , Leonetti Giuseppina , De Venuto Domenica , Gallo Crescenzio , Montemurro Pasqualina , Conese Massimo
Published: September 2019

The role of colony stimulating factors (CSFs) in cystic fibrosis (CF) circulating neutrophils has not been thoroughly evaluated, considering that the neutrophil burden of lung inflammation in these subjects is very high. The aim of this study was to assess granulocyte-CSF (G-CSF) and granulocyte-macrophage-CSF (GM-CSF) levels in CF patients in various clinical conditions and how these cytokines impact on activation and priming of neutrophils. G-CSF and GM-CSF levels were measured in sputum and serum samples of stable CF patients (n = 21) and in CF patients with acute exacerbation before and after a course of antibiotic therapy (n = 19). CSFs were tested on non CF neutrophils to investigate their effects on reactive oxygen species (ROS) production, degranulation (CD66b, elastase, lactoferrin, MMP-9), and chemotaxis. At very low concentrations found in CF patients (0.005–0.1 ng/ml), both cytokines inhibited ROS production, while higher concentrations (1–5 ng/ml) exerted a stimulatory effect. While either CSF induced elastase and MMP-9 secretion, lactoferrin levels were increased only by G-CSF. Chemotaxis was inhibited by GM-CSF, but was increased by G-CSF. However, when present together at low concentrations, CSFs increased basal and fMLP-stimulated ROS production and chemotaxis. These results suggest the CSF levels that circulating neutrophils face before extravasating into the lungs of CF patients may enhance their function contributing to the airway damage.
Multiscale analysis of hydrogen-induced softening in f.c.c. nickel single crystals oriented for multiple-slips: elastic screening effect
Authors: Ghermaoui I. M. A. , Oudriss A. , Metsue A. , Milet R. , Madani K. , Feaugas X.
Published: September 2019

Hydrogen-deformation interactions and their role in plasticity are well accepted as key features in understanding hydrogen embrittlement. In order to understand the nature of the hydrogen-induced softening process in f.c.c. metals, a substantial effort was made in this study to determine the effect of hydrogen on the tensile stress-strain behavior of nickel single crystal oriented for multiple-slips. It was clearly established that the hydrogen softening process was the result of a shielding of the elastic interactions at different scales. Hydrogen-induced softening was then formalized by a screening factor S of 0.8 ± 0.05 for 7 wppm of hydrogen, which can be incorporated into standard dislocation theory processes. The amplitude of softening suggests that the shielding process is mainly responsible for the stress softening through the formation of vacancy clusters, rather than a direct impact of hydrogen. This effect is expected to be of major importance when revisiting the impact of hydrogen on the processes causing damage to the structural alloys used in engineering.
Design, construction and characterisation of a novel nanovibrational bioreactor and cultureware for osteogenesis
Authors: Campsie Paul , Childs Peter G. , Robertson Shaun N. , Cameron Kenny , Hough James , Salmeron-Sanchez Manuel , Tsimbouri Penelope M. , Vichare Parag , Dalby Matthew J. , Reid Stuart
Published: September 2019

In regenerative medicine, techniques which control stem cell lineage commitment are a rapidly expanding field of interest. Recently, nanoscale mechanical stimulation of mesenchymal stem cells (MSCs) has been shown to activate mechanotransduction pathways stimulating osteogenesis in 2D and 3D culture. This has the potential to revolutionise bone graft procedures by creating cellular graft material from autologous or allogeneic sources of MSCs without using chemical induction. With the increased interest in mechanical stimulation of cells and huge potential for clinical use, it is apparent that researchers and clinicians require a scalable bioreactor system that provides consistently reproducible results with a simple turnkey approach. A novel bioreactor system is presented that consists of: a bioreactor vibration plate, calibrated and optimised for nanometre vibrations at 1 kHz, a power supply unit, which supplies a 1 kHz sine wave signal necessary to generate approximately 30 nm of vibration amplitude, and custom 6-well cultureware with toroidal shaped magnets incorporated in the base of each well for conformal attachment to the bioreactor’s magnetic vibration plate. The cultureware and vibration plate were designed using finite element analysis to determine the modal and harmonic responses, and validated by interferometric measurement. This helps ensure that the vibration plate and cultureware, and thus collagen and MSCs, all move as a rigid body, avoiding large deformations close to the resonant frequency of the vibration plate and vibration damping beyond the resonance. Assessment of osteogenic protein expression was performed to confirm differentiation of MSCs after initial biological experiments with the system, as well as atomic force microscopy of the 3D gel constructs during vibrational stimulation to verify that strain hardening of the gel did not occur. This shows that cell differentiation was the result of the nanovibrational stimulation provided by the bioreactor alone, and that other cell differentiating factors, such as stiffening of the collagen gel, did not contribute.