bluuebunny/crossref_metadata_2025 huggingface dataset:
Dynamics, Radiation, and Overall Energy Budget of Earthquake Rupture With Coseismic Off‐Fault Damage
Authors: Okubo Kurama , Bhat Harsha S. , Rougier Esteban , Marty Samson , Schubnel Alexandre , Lei Zhou , Knight Earl E. , Klinger Yann
Published: August 2019

Earthquake ruptures dynamically activate coseismic off‐fault damage around fault cores. Systematic field observation efforts have shown the distribution of off‐fault damage around main faults, while numerical modeling using elastic‐plastic off‐fault material models have demonstrated the evolution of coseismic off‐fault damage during earthquake ruptures. Laboratory‐scale microearthquake experiments have pointed out the enhanced high‐frequency radiation due to the coseismic off‐fault damage. However, the detailed off‐fault fracturing mechanisms, subsequent radiation, and its contribution to the overall energy budget remain to be fully understood because of limitations of current observational techniques and model formulations. Here, we constructed a new physics‐based dynamic earthquake rupture modeling framework, based on the combined finite‐discrete element method, to investigate the fundamental mechanisms of coseismic off‐fault damage, and its effect on the rupture dynamics, the radiation and the overall energy budget. We conducted a 2‐D systematic case study with depth and showed the mechanisms of dynamic activation of the coseismic off‐fault damage. We found the decrease in rupture velocity and the enhanced high‐frequency radiation in near field due to the coseismic off‐fault damage. We then evaluated the overall energy budget, which shows a significant contribution of the coseismic off‐fault damage to the overall energy budget even at depth, where the damage zone width becomes narrower. The present numerical framework for the dynamic earthquake rupture modeling thus provides new insights into earthquake rupture dynamics with the coseismic off‐fault damage.
Impact of Atmospheric Rivers on Surface Hydrological Processes in Western U.S. Watersheds
Authors: Chen Xiaodong , Leung L. Ruby , Wigmosta Mark , Richmond Marshall
Published: August 2019

Atmospheric rivers (ARs) can significantly modulate surface hydrological processes through the extreme precipitation they produce. However, there is a lack of comprehensive evaluation of ARs' impact on surface hydrology. This study uses a high‐resolution regional climate simulation to quantify the impact of ARs on surface hydrological processes across the western U.S. watersheds. The model performance is evaluated through extensive comparison against observations. Our analysis indicates that ARs produce heavy precipitation but suppress evapotranspiration. Snowpack ablates more during ARs, with higher air temperature and increased longwave radiation playing the primary and secondary roles, respectively. At the 0 °C to 10 °C temperature range, ARs increase the probability of snow ablation from 0.33 to 0.57. The runoff‐to‐precipitation ratio is primarily controlled by antecedent soil moisture, but it almost doubles in the northwestern watersheds due to the intensification of snow ablation during AR events. From the analysis of the relationship between the hydrological responses and different meteorological factors, precipitation, temperature, and radiation are identified as the key drivers that distinguish the hydrologic responses between AR and non‐AR events. Lastly, analysis of ARs and total runoff at annual scale and 1 April snowpack and winter precipitation shows that ARs explain 30% to 60% of the variability of annual total runoff and sharpen the seasonality of water resources availability in the west coast mountain watersheds.
Structure and Deformation History of the Rapidly Growing Tainan Anticline at the Deformation Front of the Taiwan Mountain Belt
Authors: Le Béon Maryline , Marc Odin , Suppe John , Huang Mong‐Han , Huang Shiuh‐Tsann , Chen Wen‐Shan
Published: August 2019

This study aims at further documenting the mechanisms of shortening at the front of fold‐and‐thrust belts. We focus on an actively growing anticline located at the deformation front of the Taiwan fold‐and‐thrust belt. Based on a multidisciplinary approach combining mainly subsurface data and geodetic techniques, we show that the Tainan anticline is a pure‐shear fault‐bend fold growing above a 38–45° west dipping back thrust, the Houchiali fault, rooted on a 3.8‐km‐deep detachment. The cumulative shortening is estimated at 2–3 km since 310 ± 50 ka, including ~30–50% of horizontal compaction shortening. The significance of the fold is little in terms of total shortening at the scale of the mountain piedmont, yet the Holocene shortening rate of 10.3 ± 1.0 mm/a accounts for 25% of the present‐day shortening rate across the piedmont. Earthquake scaling relationships applied to the Houchiali fault predict Mw~6 earthquakes that would occur a lot more frequently than indicated from historical earthquake catalogs. Hence, the aseismic slip behavior observed from geodetic measurements since two decades is a representative behavior of the fault at least at the scale of a few centuries. Our results bear out the dominance of pure‐shear folding at the front of fold‐and‐thrust belts and support horizontal compaction as a significant shortening mechanism. In contrast, the back thrust wedge structure and the aseismic slip are peculiar characteristics that likely arise from the combination of low friction and high‐pore pressure related to the thick mudstone formation hosting the wedge and of high syntectonic sedimentation rates.
The pore-forming subunit Kir6.1 of the K-ATP channel negatively regulates the NLRP3 inflammasome to control insulin resistance by interacting with NLRP3
Authors: Du Ren-Hong , Lu Ming , Wang Cong , Ding Jian-Hua , Wu Guangyu , Hu Gang
Published: August 2019

Excessive activation of the NLRP3 inflammasome is a key component contributing to the pathogenesis of various inflammatory diseases. However, the molecular mechanisms underlying its activation and regulation remain poorly defined. The objective of this study was to explore the possible function of the K+ channel pore-forming subunit Kir6.1 in regulating NLRP3 inflammasome activation and insulin resistance. Here, we demonstrate that Kir6.1 depletion markedly activates the NLRP3 inflammasome, whereas enhanced Kir6.1 expression produces opposing effects both in mice in vivo and in primary cells in vitro. We also demonstrate that Kir6.1 controls insulin resistance by inhibiting NLRP3 inflammasome activation in mice. We further show that Kir6.1 physically associates with NLRP3 and thus inhibits the interactions between the NLRP3 inflammasome subunits. Our results reveal a previously unrecognized function of Kir6.1 as a negative regulator of the NLRP3 inflammasome and insulin resistance, which is mediated by virtue of its ability to inhibit NLRP3 inflammasome assembly. These data provide novel insights into the regulatory mechanism of NLRP3 inflammasome activation and suggest that Kir6.1 is a promising therapeutic target for inflammasome-mediated inflammatory diseases.
Mutational processes contributing to the development of multiple myeloma
Authors: Hoang Phuc H. , Cornish Alex J. , Dobbins Sara E. , Kaiser Martin , Houlston Richard S.
Published: August 2019

To gain insight into multiple myeloma (MM) tumorigenesis, we analyzed the mutational signatures in 874 whole-exome and 850 whole-genome data from the CoMMpass Study. We identified that coding and non-coding regions are differentially dominated by distinct single-nucleotide variant (SNV) mutational signatures, as well as five de novo structural rearrangement signatures. Mutational signatures reflective of different principle mutational processes—aging, defective DNA repair, and apolipoprotein B editing complex (APOBEC)/activation-induced deaminase activity—characterize MM. These mutational signatures show evidence of subgroup specificity—APOBEC-attributed signatures associated withMAFtranslocation t(14;16) and t(14;20) MM; potentially DNA repair deficiency with t(11;14) and t(4;14); and aging with hyperdiploidy. Mutational signatures beyond that associated with APOBEC are independent of established prognostic markers and appear to have relevance to predicting high-risk MM.
Tens of thousands additional deaths annually in cities of China between 1.5 °C and 2.0 °C warming
Authors: Wang Yanjun , Wang Anqian , Zhai Jianqing , Tao Hui , Jiang Tong , Su Buda , Yang Jun , Wang Guojie , Liu Qiyong , Gao Chao , Kundzewicz Zbigniew W. , Zhan Mingjin , Feng Zhiqiang , Fischer Thomas
Published: August 2019

The increase in surface air temperature in China has been faster than the global rate, and more high temperature spells are expected to occur in future. Here we assess the annual heat-related mortality in densely populated cities of China at 1.5 °C and 2.0 °C global warming. For this, the urban population is projected under five SSPs, and 31 GCM runs as well as temperature-mortality relation curves are applied. The annual heat-related mortality is projected to increase from 32.1 per million inhabitants annually in 1986–2005 to 48.8–67.1 per million for the 1.5 °C warming and to 59.2–81.3 per million for the 2.0 °C warming, taking improved adaptation capacity into account. Without improved adaptation capacity, heat-related mortality will increase even stronger. If all 831 million urban inhabitants in China are considered, the additional warming from 1.5 °C to 2 °C will lead to more than 27.9 thousand additional heat-related deaths, annually.
Rhodium-catalysed direct hydroarylation of alkenes and alkynes with phosphines through phosphorous-assisted C−H activation
Authors: Wang Dingyi , Dong Ben , Wang Yandong , Qian Jiasheng , Zhu Jinjun , Zhao Yue , Shi Zhuangzhi
Published: August 2019

Biarylphosphines have been widely applied as ligands in various synthetic methods, especially in transition-metal-catalysed carbon-carbon and carbon-heteroatom bond cross-coupling reactions. Based on the outstanding properties of the parent scaffolds, a general method for in situ modification of the commercial tertiary phosphine ligands to access a series of ligands is in high demand. Here we show that a rhodium-catalysed system is introduced for the hydroarylation of alkenes and alkynes with tertiary phosphines through P(III)-chelation assisted C-H activation. A series of ligand libraries containing alkyl and alkenyl substituted groups with different steric and electronic properties are obtained in high yields. Furthermore, several experimental studies are performed to uncover the key mechanistic features of the linear-selective hydroarylation of alkenes and branch-selective hydroarylation of alkynes.
Tailoring the photoelectrochemistry of catalytic metal-insulator-semiconductor (MIS) photoanodes by a dissolution method
Authors: Loget G. , Mériadec C. , Dorcet V. , Fabre B. , Vacher A. , Fryars S. , Ababou-Girard S.
Published: August 2019

Apart from being key structures of modern microelectronics, metal-insulator-semiconductor (MIS) junctions are highly promising electrodes for artificial leaves, i.e. photoelectrochemical cells that can convert sunlight into energy-rich fuels. Here, we demonstrate that homogeneous Si/SiOx/Ni MIS junctions, employed as photoanodes, can be functionalized with a redox-active species and simultaneously converted into high-photovoltage inhomogeneous MIS junctions by electrochemical dissolution. We also report on the considerable enhancement of performance towards urea oxidation, induced by this process. Finally, we demonstrate that both phenomena can be employed synergistically to design highly-efficient Si-based photoanodes. These findings open doors for the manufacturing of artificial leaves that can generate H2 under solar illumination using contaminated water.
Haploinsufficiency in the ANKS1B gene encoding AIDA-1 leads to a neurodevelopmental syndrome
Authors: Carbonell Abigail U. , Cho Chang Hoon , Tindi Jaafar O. , Counts Pamela A. , Bates Juliana C. , Erdjument-Bromage Hediye , Cvejic Svetlana , Iaboni Alana , Kvint Ifat , Rosensaft Jenny , Banne Ehud , Anagnostou Evdokia , Neubert Thomas A. , Scherer Stephen W. , Molholm Sophie , Jordan Bryen A.
Published: August 2019

Neurodevelopmental disorders, including autism spectrum disorder, have complex polygenic etiologies. Single-gene mutations in patients can help define genetic factors and molecular mechanisms underlying neurodevelopmental disorders. Here we describe individuals with monogenic heterozygous microdeletions in ANKS1B, a predicted risk gene for autism and neuropsychiatric diseases. Affected individuals present with a spectrum of neurodevelopmental phenotypes, including autism, attention-deficit hyperactivity disorder, and speech and motor deficits. Neurons generated from patient-derived induced pluripotent stem cells demonstrate loss of the ANKS1B-encoded protein AIDA-1, a brain-specific protein highly enriched at neuronal synapses. A transgenic mouse model of Anks1b haploinsufficiency recapitulates a range of patient phenotypes, including social deficits, hyperactivity, and sensorimotor dysfunction. Identification of the AIDA-1 interactome using quantitative proteomics reveals protein networks involved in synaptic function and the etiology of neurodevelopmental disorders. Our findings formalize a link between the synaptic protein AIDA-1 and a rare, previously undefined genetic disease we term ANKS1B haploinsufficiency syndrome.
Rapid fabrication of vascularized and innervated cell-laden bone models with biomimetic intrafibrillar collagen mineralization
Authors: Thrivikraman Greeshma , Athirasala Avathamsa , Gordon Ryan , Zhang Limin , Bergan Raymond , Keene Douglas R. , Jones James M. , Xie Hua , Chen Zhiqiang , Tao Jinhui , Wingender Brian , Gower Laurie , Ferracane Jack L. , Bertassoni Luiz E.
Published: August 2019

Bone tissue, by definition, is an organic–inorganic nanocomposite, where metabolically active cells are embedded within a matrix that is heavily calcified on the nanoscale. Currently, there are no strategies that replicate these definitive characteristics of bone tissue. Here we describe a biomimetic approach where a supersaturated calcium and phosphate medium is used in combination with a non-collagenous protein analog to direct the deposition of nanoscale apatite, both in the intra- and extrafibrillar spaces of collagen embedded with osteoprogenitor, vascular, and neural cells. This process enables engineering of bone models replicating the key hallmarks of the bone cellular and extracellular microenvironment, including its protein-guided biomineralization, nanostructure, vasculature, innervation, inherent osteoinductive properties (without exogenous supplements), and cell-homing effects on bone-targeting diseases, such as prostate cancer. Ultimately, this approach enables fabrication of bone-like tissue models with high levels of biomimicry that may have broad implications for disease modeling, drug discovery, and regenerative engineering.
The antimicrobial peptide thanatin disrupts the bacterial outer membrane and inactivates the NDM-1 metallo-β-lactamase
Authors: Ma Bo , Fang Chao , Lu Linshan , Wang Mingzhi , Xue Xiaoyan , Zhou Ying , Li Mingkai , Hu Yue , Luo Xiaoxing , Hou Zheng
Published: August 2019

New Delhi metallo-β-lactamase-1 (NDM-1) is the most prevalent type of metallo-β-lactamase and hydrolyzes almost all clinically used β-lactam antibiotics. Here we show that the antimicrobial peptide thanatin disrupts the outer membrane of NDM-1-producing bacteria by competitively displacing divalent cations on the outer membrane and inducing the release of lipopolysaccharides. In addition, thanatin inhibits the enzymatic activity of NDM-1 by displacing zinc ions from the active site, and reverses carbapenem resistance in NDM-1-producing bacteria in vitro and in vivo. Thus, thanatin’s dual mechanism of action may be useful for combating infections caused by NDM-1-producing pathogens.
Direct atomic insight into the role of dopants in phase-change materials
Authors: Zhu Min , Song Wenxiong , Konze Philipp M. , Li Tao , Gault Baptiste , Chen Xin , Shen Jiabin , Lv Shilong , Song Zhitang , Wuttig Matthias , Dronskowski Richard
Published: August 2019

Doping is indispensable to tailor phase-change materials (PCM) in optical and electronic data storage. Very few experimental studies, however, have provided quantitative information on the distribution of dopants on the atomic-scale. Here, we present atom-resolved images of Ag and In dopants in Sb2Te-based (AIST) PCM using electron microscopy and atom-probe tomography. Combing these with DFT calculations and chemical-bonding analysis, we unambiguously determine the dopants’ role upon recrystallization. Composition profiles corroborate the substitution of Sb by In and Ag, and the segregation of excessive Ag into grain boundaries. While In is bonded covalently to neighboring Te, Ag binds ionically. Moreover, In doping accelerates the crystallization and hence operation while Ag doping limits the random diffusion of In atoms and enhances the thermal stability of the amorphous phase.
Structural basis for the target specificity of actin histidine methyltransferase SETD3
Authors: Dai Shaobo , Horton John R. , Woodcock Clayton B. , Wilkinson Alex W. , Zhang Xing , Gozani Or , Cheng Xiaodong
Published: August 2019

SETD3 is an actin histidine-N3 methyltransferase, whereas other characterized SET-domain enzymes are protein lysine methyltransferases. We report that in a pre-reactive complex SETD3 binds the N3-protonated form (N3-H) of actin His73, and in a post-reactive product complex, SETD3 generates the methylated histidine in an N1-protonated (N1-H) and N3-methylated form. During the reaction, the imidazole ring of His73 rotates ~105°, which shifts the proton from N3 to N1, thus ensuring that the target atom N3 is deprotonated prior to the methyl transfer. Under the conditions optimized for lysine deprotonation, SETD3 has weak lysine methylation activity on an actin peptide in which the target His73 is substituted by a lysine. The structure of SETD3 with Lys73-containing peptide reveals a bent conformation of Lys73, with its side chain aliphatic carbons tracing along the edge of imidazole ring and the terminal ε-amino group occupying a position nearly identical to the N3 atom of unmethylated histidine.
Publisher Correction: Development of an immunodeficient pig model allowing long-term accommodation of artificial human vascular tubes
Authors: Itoh Manabu , Mukae Yosuke , Kitsuka Takahiro , Arai Kenichi , Nakamura Anna , Uchihashi Kazuyoshi , Toda Shuji , Matsubayashi Kumika , Oyama Jun-ichi , Node Koichi , Kami Daisuke , Gojo Satoshi , Morita Shigeki , Nishida Takahiro , Nakayama Koichi , Kobayashi Eiji
Published: August 2019

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
3D non-isothermal phase-field simulation of microstructure evolution during selective laser sintering
Authors: Yang Yangyiwei , Ragnvaldsen Olav , Bai Yang , Yi Min , Xu Bai-Xiang
Published: August 2019

During selective laser sintering (SLS), the microstructure evolution and local temperature variation interact mutually. Application of conventional isothermal sintering model is thereby insufficient to describe SLS. In this work, we construct our model from entropy level, and derive the non-isothermal kinetics for order parameters along with the heat transfer equation coupled with microstructure evolution. Influences from partial melting and laser-powder interaction are also addressed. We then perform 3D finite element non-isothermal phase-field simulations of the SLS single scan. To confront the high computation cost, we propose a novel algorithm analogy to minimum coloring problem and manage to simulate a system of 200 grains with grain tracking algorithm using as low as 8 non-conserved order parameters. Specifically, applying the model to SLS of the stainless steel 316L powder, we identify the influences of laser power and scan speed on microstructural features, including the porosity, surface morphology, temperature profile, grain geometry, and densification. We further validate the first-order kinetics of the transient porosity during densification, and demonstrate the applicability of the developed model in predicting the linkage of densification factor to the specific energy input during SLS.
Evaluating relevance and redundancy to quantify how binary node metadata interplay with the network structure
Authors: Cinelli Matteo , Ferraro Giovanna , Iovanella Antonio
Published: August 2019

Networks are real systems modelled through mathematical objects made up of nodes and links arranged into peculiar and deliberate (or partially deliberate) topologies. Studying these real-world topologies allows for several properties of interest to be revealed. In real networks, nodes are also identified by a certain number of non-structural features or metadata. Given the current possibility of collecting massive quantity of such metadata, it becomes crucial to identify automatically which are the most relevant for the observed structure. We propose a new method that, independently from the network size, is able to not only report the relevance of binary node metadata, but also rank them. Such a method can be applied to networks from any domain, and we apply it in two heterogeneous cases: a temporal network of technology transfer and a protein-protein interaction network. Together with the relevance of node metadata, we investigate the redundancy of these metadata displaying by the results on a Redundancy-Relevance diagram, which is able to highlight the differences among vectors of metadata from both a structural and a non-structural point of view. The obtained results provide insights of a practical nature into the importance of the observed node metadata for the actual network structure.
Electro-haptic enhancement of speech-in-noise performance in cochlear implant users
Authors: Fletcher Mark D. , Hadeedi Amatullah , Goehring Tobias , Mills Sean R.
Published: August 2019

Cochlear implant (CI) users receive only limited sound information through their implant, which means that they struggle to understand speech in noisy environments. Recent work has suggested that combining the electrical signal from the CI with a haptic signal that provides crucial missing sound information (“electro-haptic stimulation”; EHS) could improve speech-in-noise performance. The aim of the current study was to test whether EHS could enhance speech-in-noise performance in CI users using: (1) a tactile signal derived using an algorithm that could be applied in real time, (2) a stimulation site appropriate for a real-world application, and (3) a tactile signal that could readily be produced by a compact, portable device. We measured speech intelligibility in multi-talker noise with and without vibro-tactile stimulation of the wrist in CI users, before and after a short training regime. No effect of EHS was found before training, but after training EHS was found to improve the number of words correctly identified by an average of 8.3%-points, with some users improving by more than 20%-points. Our approach could offer an inexpensive and non-invasive means of improving speech-in-noise performance in CI users.
Strong genetic isolation of the black-lipped pearl oyster (Pinctada margaritifera) in the Marquesas archipelago (French Polynesia)
Authors: Reisser Céline , Lo Cédrik , Schikorski David , Sham Koua Manaarii , Planes Serge , Ky Chin-Long
Published: August 2019

The French Polynesian islands are internationally known for their black pearls, produced by culture of the black lipped pearl oysterPinctada margaritifera. The ongoing development of hatcheries forP.margaritiferain French Polynesia poses new challenges for the industry, particularly regarding the maintenance of genetic diversity in the hatchery stocks. This emphasizes the necessity to characterize the genetic diversity and differentiation within natural and exploited populations, to carefully select putative parental populations. The present study aimed at validating the phylogenetic status and investigating genetic attributes of populations from the only two non-exploited archipelagos of French Polynesia, the Marquesas archipelago, and the Australes archipelago, never analysed before. We found that individuals from both archipelagos belonged toP.margaritiferaspecies. However, while the Australes population was genetically similar to non-exploited populations of the Tuamotu, the Marquesas populations were highly differentiated from the rest of the populations. This differentiation cannot not be only attributed to geographic distance and aquaculture status, but likely to hydrodynamic barriers allowing vicariant events to take place. Our results add up to other studies describing the Marquesas archipelago as a hotspot for biodiversity and differentiation, with some of the highest levels of endemism and vicariance found among marine species worldwide and provide precious information on available genetic resources for the implementation ofP.margaritiferaselective breeding and its genetic conservation in French Polynesia.
Efficient Alpha Radiation Detector using Low Temperature Hydrothermally Grown ZnO:Ga Nanorod Scintillator
Authors: Sahani R. M. , Kumari Chandni , Pandya Arun , Dixit Ambesh
Published: August 2019

We report efficient detection of alpha radiation on highly textured and vertically aligned along (002) Gallium-doped Zinc Oxide (ZnO:Ga) nanorods on a glass substrate with an average diameter ~150 ± 10 nm. Photoluminescence measurement showed near band emission 393 nm, in agreement with the bandgap value ~3.22 eV, measured by UV-Vis spectroscopy. The developed ZnO:Ga nanorod scintillator is coupled with a commercially available photomultiplier tube and 1K Multichannel Analyser to fabricate an alpha radiation detector. The performance of the alpha radiation detector is evaluated using various activities alpha radiation sources. A large pulse height spectrum is recorded by the detector for different alpha sources against the background spectrum. The calculated detection efficiency and Minimum Detectable Activity (MDA) showed that the detector is highly sensitive to alpha radiation. The repeatability and reproducibility of the performance are studied by evaluating the response of a single scintillator for numerous exposures and by studying inter-batch response variations, respectively. The response is repeatable within ±1% whereas reproducibility varies from ±20% for extremely low activity alpha sources to ±5% for high activity alpha sources. The performance of ZnO:Ga nanorod scintillator grown on glass substrate demonstrates that it can be a promising material system for the detection of alpha radiation.
The role of ESCO2, SALL4 and TBX5 genes in the susceptibility to thalidomide teratogenesis
Authors: Gomes Julia do Amaral , Kowalski Thayne Woycinck , Fraga Lucas Rosa , Macedo Gabriel S. , Sanseverino Maria Teresa Vieira , Schuler-Faccini Lavínia , Vianna Fernanda Sales Luiz
Published: August 2019

Thalidomide is widely used for several diseases; however, it causes malformations in embryos exposed during pregnancy. The complete understanding of the mechanisms by which thalidomide affects the embryo development has not yet been obtained. The phenotypic similarity makes TE a phenocopy of syndromes caused by mutations in ESCO2, SALL4 and TBX5 genes. Recently, SALL4 and TBX5 were demonstrated to be thalidomide targets. To understand if these genes act in the TE development, we sequenced them in 27 individuals with TE; we verified how thalidomide affect them in human pluripotent stem cells (hPSCs) through a differential gene expression (DGE) analysis from GSE63935; and we evaluated how these genes are functionally related through an interaction network analysis. We identified 8 variants in ESCO2, 15 in SALL4 and 15 in TBX5. We compared allelic frequencies with data from ExAC, 1000 Genomes and ABraOM databases; eight variants were significantly different (p < 0.05). Eleven variants in SALL4 and TBX5 were previously associated with cardiac diseases or malformations; however, in TE sample there was no association. Variant effect prediction tools showed 97% of the variants with potential to influence in these genes regulation. DGE analysis showed a significant reduction of ESCO2 in hPSCs after thalidomide exposure.
Dual-active antifungal agents containing strobilurin and SDHI-based pharmacophores
Authors: Zuccolo Marco , Kunova Andrea , Musso Loana , Forlani Fabio , Pinto Andrea , Vistoli Giulio , Gervasoni Silvia , Cortesi Paolo , Dallavalle Sabrina
Published: August 2019

Crop disease management often implies repeated application of fungicides. However, the increasing emergence of fungicide-resistant pathogens requires their rotation or combined use. Tank-mix combinations using fungicides with different modes of action are often hard to manage by farmers. An alternative and unexploited strategy are bifunctional fungicides, i.e. compounds resulting from conjugation of the pharmacophores of fungicides with different mechanisms of action. In this paper we describe a new approach to antifungal treatments based on the synthesis of dual agents, obtained by merging the strobilurin and succinate dehydrogenase inhibitor pharmacophores into a new entity. The compounds were tested against important fungal plant pathogens and showed good inhibition of Pyricularia oryzae and Sclerotinia sclerotiorum with activity comparable to commercial fungicides. The inhibition of the cytochrome bc1 and the succinate dehydrogenase enzyme activity confirmed that the new molecules are endowed with a dual mechanism of action. These results were further supported by molecular modelling which showed that selected compounds form stable complexes with both cytochrome b subunit and succinate dehydrogenase enzyme. This work can be considered an important first step towards the development of novel dual-action agents with optimized structure and improved interaction with the targets.
DeepInsight: A methodology to transform a non-image data to an image for convolution neural network architecture
Authors: Sharma Alok , Vans Edwin , Shigemizu Daichi , Boroevich Keith A. , Tsunoda Tatsuhiko
Published: August 2019

It is critical, but difficult, to catch the small variation in genomic or other kinds of data that differentiates phenotypes or categories. A plethora of data is available, but the information from its genes or elements is spread over arbitrarily, making it challenging to extract relevant details for identification. However, an arrangement of similar genes into clusters makes these differences more accessible and allows for robust identification of hidden mechanisms (e.g. pathways) than dealing with elements individually. Here we propose, DeepInsight, which converts non-image samples into a well-organized image-form. Thereby, the power of convolution neural network (CNN), including GPU utilization, can be realized for non-image samples. Furthermore, DeepInsight enables feature extraction through the application of CNN for non-image samples to seize imperative information and shown promising results. To our knowledge, this is the first work to apply CNN simultaneously on different kinds of non-image datasets: RNA-seq, vowels, text, and artificial.
Water versus Asphaltenes; Liquid–Liquid and Solid–Liquid Molecular Interactions Unravel the Mechanisms behind an Improved Oil Recovery Methodology
Authors: Joonaki Edris , Buckman Jim , Burgass Rod , Tohidi Bahman
Published: August 2019

Understanding of possible molecular interactions at liquid-liquid and solid-liquid interfaces can shed lights onto the nature’s design and authorise fine manipulation aptitude in biological, manufacturing, microfluidic and oil recovery applications. Of particular interest is the capability to control the aggregation of organic and biological macromolecules, which typically poses significant challenges for oil industry and human life, respectively. Following asphaltene aggregation phenomenon through π-stacking and hydrogen bonding interactions, asphaltene aggregates can form a thin layer at the crude oil-brine interface through noncovalent interactions such as -O-H···O hydrogen bonds and/or alter the wettability state of the solid surface from initially water-wet into mixed-oil wetting. Here, we probe the impact of water with variety of salinities and ion types on formation of water in oil micro-emulsions, asphaltene deposition, and induced water wettability transition at micro scale. For the first time we investigate the influence of water in oil micro-emulsions on asphaltene aggregation and deposition phenomena at elevated pressure and temperature conditions. We also monitor the micro-wettability alterations of gold surface of the QCM owing to ion valency/concentration changes using state of the art ESEM imaging facility. Our results depict that owing to the substitution of divalent cations with monovalent ones, asphaltene deposition is repelled and the solid surface becomes more hydrophilic, proposing a generalizable strategy to control wettability and an elucidation for the profitability of so-called low salinity water flooding, an enhanced oil recovery methodology. For the biological applications, this study provides insights into the potential roles of ions and hydrogen bonds in the protein deposition in tissues and self-assembly interactions and efficiency of drugs against protein aggregation drivers.
Parenting Stress Undermines Mother-Child Brain-to-Brain Synchrony: A Hyperscanning Study
Authors: Azhari A. , Leck W. Q. , Gabrieli G. , Bizzego A. , Rigo P. , Setoh P. , Bornstein M. H. , Esposito G.
Published: August 2019

Synchrony refers to the coordinated interplay of behavioural and physiological signals that reflect the bi-directional attunement of one partner to the other’s psychophysiological, cognitive, emotional, and behavioral state. In mother-child relationships, a synchronous pattern of interaction indicates parental sensitivity. Parenting stress has been shown to undermine mother-child behavioural synchrony. However, it has yet to be discerned whether parenting stress affects brain-to-brain synchrony during everyday joint activities. Here, we show that greater parenting stress is associated with less brain-to-brain synchrony in the medial left cluster of the prefrontal cortex when mother and child engage in a typical dyadic task of watching animation videos together. This brain region overlaps with the inferior frontal gyrus, the frontal eye field, and the dorsolateral prefrontal cortex, which are implicated in inference of mental states and social cognition. Our result demonstrates the adverse effect of parenting stress on mother-child attunement that is evident at a brain-to-brain level. Mother-child brain-to-brain asynchrony may underlie the robust association between parenting stress and poor dyadic co-regulation. We anticipate our study to form the foundation for future investigations into mechanisms by which parenting stress impairs the mother-child relationship.
Insects to feed insects - feeding Aedes mosquitoes with flies for laboratory rearing
Authors: Bimbilé Somda Nanwintoum Séverin , Maïga Hamidou , Mamai Wadaka , Yamada Hanano , Ali Adel , Konczal Anna , Gnankiné Olivier , Diabaté Abdoulaye , Sanon Antoine , Dabiré Kounbobr Roch , Gilles Jérémie R. L. , Bouyer Jérémy
Published: August 2019

The black soldier fly, yellow mealworm and house fly are known for their wide distribution, ease of breeding, and environmental and nutritional attributes. Diets based on these fly proteins for the rearing of mosquito larvae are more accessible and affordable when compared to the reference IAEA diet which consists largely of costly livestock products such as bovine liver powder. Following a step-by-step assessment, we developed diet mixtures based on insect meal for the optimal mass production of Aedes albopictus and Ae. aegypti. Based on the assessed parameters including mosquito egg hatch, body size, flight ability, longevity and diet cost reduction, two mixtures are recommended: 1/2 tuna meal (TM) + 7/20 black soldier fly (BSF) + 3/20 brewer’s yeast and 1/2 TM + 1/2 BSF. These findings, which could be adapted to other mosquito species, provide alternative protein sources for mass rearing insects for genetic control strategies.
European propolis is highly active against trypanosomatids including Crithidia fasciculata
Authors: Alotaibi Abdullah , Ebiloma Godwin U. , Williams Roderick , Alenezi Samya , Donachie Anne-Marie , Guillaume Selome , Igoli John O. , Fearnley James , de Koning Harry P. , Watson David G.
Published: August 2019

Extracts of 35 samples of European propolis were tested against wild type and resistant strains of the protozoal pathogens Trypanosoma brucei, Trypanosoma congolense and Leishmania mexicana. The extracts were also tested against Crithidia fasciculata a close relative of Crithidia mellificae, a parasite of bees. Crithidia, Trypanosoma and Leishmania are all members of the order Kinetoplastida. High levels of activity were obtained for all the samples with the levels of activity varying across the sample set. The highest levels of activity were found against L. mexicana. The propolis samples were profiled by using liquid chromatography with high resolution mass spectrometry (LC-MS) and principal components analysis (PCA) of the data obtained indicated there was a wide variation in the composition of the propolis samples. Orthogonal partial least squares (OPLS) associated a butyrate ester of pinobanksin with high activity against T. brucei whereas in the case of T. congolense high activity was associated with methyl ethers of chrysin and pinobanksin. In the case of C. fasciculata highest activity was associated with methyl ethers of galangin and pinobanksin. OPLS modelling of the activities against L. mexicana using the mass spectrometry produced a less successful model suggesting a wider range of active components.
Multiplexed Adaptive RT-PCR Based on L-DNA Hybridization Monitoring for the Detection of Zika, Dengue, and Chikungunya RNA
Authors: Euliano Erin M. , Hardcastle Austin N. , Victoriano Christia M. , Gabella William E. , Haselton Frederick R. , Adams Nicholas M.
Published: August 2019

Reverse transcription polymerase chain reaction (RT-PCR) is the gold standard for the molecular diagnosis of many infectious diseases, including RNA viruses, but is generally limited to settings with access to trained personnel and laboratory resources. We have previously reported a fundamentally simpler thermal cycling platform called Adaptive PCR, which dynamically controls thermal cycling conditions during each cycle by optically monitoring the annealing and melting of mirror-image L-DNA surrogates of the PCR primers and targets. In this report, we integrate optically-controlled reverse transcription and single-channel monitoring of L-DNAs to develop a multiplexed Adaptive RT-PCR instrument and assay for the detection of Zika, dengue, and chikungunya virus RNA with high target specific and low limits of detection. The assay is demonstrated to detect as low as 5 copies/reaction of Zika or chikungunya RNA and 50 copies/reaction of dengue RNA. The multiplexed Adaptive RT-PCR instrument is robust and has many of the features required to implement diagnostic assays for RNA viruses in settings that lack traditional laboratory resources.
Identification of alkaline pH optimum of human glucokinase because of ATP-mediated bias correction in outcomes of enzyme assays
Authors: Šimčíková Daniela , Heneberg Petr
Published: August 2019

Adenosine triphosphate (ATP) is a crucial substrate and energy source commonly used in enzyme reactions. However, we demonstrated that the addition of this acidic compound to enzyme assay buffers can serve as a source of unnoticed pH changes. Even relatively low concentrations of ATP (up to 5 mM) shifted pH of reaction mixtures to acidic values. For example, Tris buffer lost buffering capacity at pH 7.46 by adding ATP at a concentration higher than 2 mM. In addition to the buffering capacity, the pH shifts differed with respect to the buffer concentration. High ATP concentrations are commonly used in hexokinase assays. We demonstrated how the presence of ATP affects pH of widely used enzyme assay buffers and inversely affected KM of human hexokinase 2 and S0.5 of human glucokinase. The pH optimum of human glucokinase was never reported before. We found that previously reported optimum of mammalian glucokinase was incorrect, affected by the ATP-induced pH shifts. The pH optimum of human glucokinase is at pH 8.5–8.7. Suggested is the full disclosure of reaction conditions, including the measurement of pH of the whole reaction mixtures instead of measuring pH prior to the addition of all the components.
ABCG1 contributes to suberin formation in Arabidopsis thaliana roots
Authors: Shanmugarajah Kalpana , Linka Nicole , Gräfe Katharina , Smits Sander H. J. , Weber Andreas P. M. , Zeier Jürgen , Schmitt Lutz
Published: August 2019

Diffusion barriers enable plant survival under fluctuating environmental conditions. They control internal water potential and protect against biotic or abiotic stress factors. How these protective molecules are deposited to the extracellular environment is poorly understood. We here examined the role of the Arabidopsis ABC half-size transporter AtABCG1 in the formation of the extracellular root suberin layer. Quantitative analysis of extracellular long-chain fatty acids and aliphatic alcohols in the atabcg1 mutants demonstrated altered root suberin composition, specifically a reduction in longer chain dicarboxylic acids, fatty alcohols and acids. Accordingly, the ATP-hydrolyzing activity of heterologous expressed and purified AtABCG1 was strongly stimulated by fatty alcohols (C26–C30) and fatty acids (C24–C30) in a chain length dependent manner. These results are a first indication for the function of AtABCG1 in the transport of longer chain aliphatic monomers from the cytoplasm to the apoplastic space during root suberin formation.
Inhibition of Francisella tularensis phagocytosis using a novel anti-LPS scFv antibody fragment
Authors: Mechaly Adva , Elia Uri , Alcalay Ron , Cohen Hila , Epstein Eyal , Cohen Ofer , Mazor Ohad
Published: August 2019

Francisella tularensis (Ft), the causative agent of lethal tularemia, is classified as a category A biological warfare threat agent. While Ft infection is treatable by antibiotics, many failed antibiotic treatments were reported, highlighting the need for effective new treatments. It has been demonstrated that binding of antibody-coated bacteria to the Fc receptor located on phagocytic cells is a key process needed for efficient protection against Ft. Yet, Ft utilizes the same receptor to enter the phagocytic cells in order to escape the immune system. To address the question whether an anti-Ft LPS antibody lacking the ability to bind the Fc receptor may inhibit the entry of Ft into host cells, a soluble scFv (TL1-scFv) was constructed from an anti Ft-LPS antibody (TL1) that was isolated from an immune single-chain (scFv) phage-display library. Bacterial uptake was assessed upon infection of macrophages with Ft live attenuated strain (LVS) in the presence of either TL1 or TL1-scFv. While incubation of LVS in the presence of TL1 greatly enhanced bacterial uptake, LVS uptake was significantly inhibited in the presence of TL1-scFv. These results prompt further experiments probing the therapeutic efficacy of TL1-scFv, alone or in combination with antibiotic treatment.
Nonlinear optical characterization of copper oxide nanoellipsoids
Authors: Boltaev Ganjaboy S. , Ganeev Rashid A. , Krishnendu P. S. , Zhang Ke , Guo Chunlei
Published: August 2019

Recently, nonspherical nanoparticles took attention due to advanced properties of these structures. We report the study of the nonlinear optical properties of copper oxide nanoellipsoids using 800 nm and 400 nm, 60 fs pulses. The optical limiting effect of copper oxide nanoellipsoids is analyzed. The influence of band gap of copper nanoparticles and copper oxide nanoellipsoids on their nonlinear optical response was studied. For the first time, the low- and high-order nonlinear optical responses of copper nanoellipsoids were studied. The magnitudes of nonlinear optical parameters of the suspension of copper oxide nanoellipsoids were measured to be γ = 1.23 × 10−15 cm2 W−1, and β = 1.0 × 10−11 cm W−1 respectively. We observed the four-fold enhancement of the nonlinear optical refraction of copper oxide nanoellipsoids at the wavelength of 400 nm, 60 fs probe pulses compared to 800 nm radiation. We also analyzed the high-order nonlinear response of CuO nanoellipsoids through generation of high-order harmonics of 800 nm, 60 fs pulses in the plasmas produced during laser ablation of the nanoellipsoid-contained targets. We demonstrated the harmonics up to the 35th order (E = 50 eV) in case of single-color pump and 24th (30 eV) in case of two-color pump.
Xeno-free and feeder-free culture and differentiation of human embryonic stem cells on recombinant vitronectin-grafted hydrogels
Authors: Chen Li-Hua , Sung Tzu-Cheng , Lee Henry Hsin-Chung , Higuchi Akon , Su Huan-Chiao , Lin Kuan-Ju , Huang Yu-Ru , Ling Qing-Dong , Kumar S. Suresh , Alarfaj Abdullah A. , Munusamy Murugan A. , Nasu Michiyo , Chen Da-Chung , Hsu Shih-Tien , Chang Yung , Lee Kuei-Fang , Wang Han-Chow , Umezawa Akihiro
Published: August 2019

Xeno-free culture and cardiomyocyte differentiation of human embryonic stem cells on vitronectin-grafted hydrogels by adjusting surface charge and elasticity.
The topography of fibrous scaffolds modulates the paracrine function of Ad-MSCs in the regeneration of skin tissues
Authors: Huang Ruiying , Wang Jian , Chen Haoxiang , Shi Xuelei , Wang Xiaocheng , Zhu Yonghua , Tan Zhikai
Published: August 2019

A tissue engineered skin is designed and fabricated by 3D printing, which has a therapeutic effect on wound healing and skin tissue regeneration.
Self-assembly of M4L4tetrahedral cages incorporating pendant PS and PSe functionalised ligands
Authors: Butler Patrick W. V. , Kruger Paul E. , Ward Jas S.
Published: August 2019

The synthesis and study of metal–organic tetrahedral cages incorporating flexible thio- and selenophosphate-based ligands.
Wrinkling and failure behavior of single-layer MoS2 sheets under in-plane shear
Authors: Li Yao , Chen Peijian , Liu Hao , Peng Juan , Gao Feng , Luo Ning
Published: August 2019

In this paper, the wrinkling and failure behavior of single layer MoS2 (SLMoS2) sheets under in-plane shear is investigated using molecular simulations and the nonlocal model.
A proton transfer mechanism along the PO4 anion chain in the [Zn(HPO4)(H2PO4)]2− coordination polymer
Authors: Dong Hieu C. , Hoang Hieu T. , Tran Dinh Manh , Phan Thang B. , Bureekaew Sareeya , Kawazoe Yoshiyuki , Le Hung M.
Published: August 2019

In this study, we revisit the proton transfer mechanism in [Zn(HPO4)(H2PO4)]2−, a coordination polymer possessing high proton conductivity.
MXene as a non-metal charge mediator in 2D layered CdS@Ti3C2@TiO2 composites with superior Z-scheme visible light-driven photocatalytic activity
Authors: Liu Qiaoran , Tan Xiaoyao , Wang Shaobin , Ma Fang , Znad Hussin , Shen Zhangfeng , Liu Lihong , Liu Shaomin
Published: August 2019

Z-Scheme CdS@Ti3C2@TiO2 nanohybrids using MXene Ti3C2 as a non-metal charge carrier mediator exhibited superior performance in sulfachloropyridazine degradation.
Exploring variability in detection thresholds of microparticles through participant characteristics
Authors: Santagiuliana Marco , Marigómez Inés Sampedro , Broers Layla , Hayes John E. , Piqueras-Fiszman Betina , Scholten Elke , Stieger Markus
Published: August 2019

This study investigated how product familiarity and physiological characteristics of participants affect detectability of microparticles in viscous and semi-solid foods.
Impact of different roasting conditions on chemical composition, sensory quality and physicochemical properties of waxy-barley products
Authors: Schlörmann W. , Zetzmann S. , Wiege B. , Haase N. U. , Greiling A. , Lorkowski S. , Dawczynski C. , Glei M.
Published: August 2019

Roasting improves sensory properties and differentially modulates health-related compounds of barley products.