bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification and replication of RNA-Seq gene network modules associated with depression severity
Authors: Le Trang T. , Savitz Jonathan , Suzuki Hideo , Misaki Masaya , Teague T. Kent , White Bill C. , Marino Julie H. , Wiley Graham , Gaffney Patrick M. , Drevets Wayne C. , McKinney Brett A. , Bodurka Jerzy
Published: September 2018

Genomic variation underlying major depressive disorder (MDD) likely involves the interaction and regulation of multiple genes in a network. Data-driven co-expression network module inference has the potential to account for variation within regulatory networks, reduce the dimensionality of RNA-Seq data, and detect significant gene-expression modules associated with depression severity. We performed an RNA-Seq gene co-expression network analysis of mRNA data obtained from the peripheral blood mononuclear cells of unmedicated MDD (n = 78) and healthy control (n = 79) subjects. Across the combined MDD and HC groups, we assigned genes into modules using hierarchical clustering with a dynamic tree cut method and projected the expression data onto a lower-dimensional module space by computing the single-sample gene set enrichment score of each module. We tested the single-sample scores of each module for association with levels of depression severity measured by the Montgomery-Åsberg Depression Scale (MADRS). Independent of MDD status, we identified 23 gene modules from the co-expression network. Two modules were significantly associated with the MADRS score after multiple comparison adjustment (adjustedp = 0.009, 0.028 at 0.05 FDR threshold), and one of these modules replicated in a previous RNA-Seq study of MDD (p = 0.03). The two MADRS-associated modules contain genes previously implicated in mood disorders and show enrichment of apoptosis and B cell receptor signaling. The genes in these modules show a correlation between network centrality and univariate association with depression, suggesting that intramodular hub genes are more likely to be related to MDD compared to other genes in a module.
Inhibition of TRF2 accelerates telomere attrition and DNA damage in naïve CD4 T cells during HCV infection
Authors: Nguyen Lam Nhat , Zhao Juan , Cao Dechao , Dang Xindi , Wang Ling , Lian Jianqi , Zhang Ying , Jia Zhansheng , Wu Xiao Y. , Morrison Zheng , Xie Qian , Ji Yingjie , Zhang Zheng , El Gazzar Mohamed , Ning Shunbin , Moorman Jonathan P. , Yao Zhi Q.
Published: September 2018

T cells play a crucial role in viral clearance and vaccine responses; however, the mechanisms that regulate their homeostasis during viral infections remain unclear. In this study, we investigated the machineries of T-cell homeostasis and telomeric DNA damage using a human model of hepatitis C virus (HCV) infection. We found that naïve CD4 T cells in chronically HCV-infected patients (HCV T cells) were significantly reduced due to apoptosis compared with age-matched healthy subjects (HSs). These HCV T cells were not only senescent, as demonstrated by overexpression of aging markers and particularly shortened telomeres; but also DNA damaged, as evidenced by increased dysfunctional telomere-induced foci (TIF). Mechanistically, the telomere shelterin protein, in particular telomeric repeat binding factor 2 (TRF2) that functions to protect telomeres from DNA damage, was significantly inhibited posttranscriptionally via the p53-dependent Siah-1a ubiquitination. Importantly, knockdown of TRF2 in healthy T cells resulted in increases in telomeric DNA damage and T-cell apoptosis, whereas overexpression of TRF2 in HCV T cells alleviated telomeric DNA damage and T-cell apoptosis. To the best of our knowledge, this is the first report revealing that inhibition of TRF2 promotes T-cell telomere attrition and telomeric DNA damage that accelerates T-cell senescent and apoptotic programs, which contribute to naïve T-cell loss during viral infection. Thus, restoring the impaired T-cell telomeric shelterin machinery may offer a new strategy to improve immunotherapy and vaccine response against human viral diseases.
Polyphyllin I suppresses the formation of vasculogenic mimicry via Twist1/VE-cadherin pathway
Authors: Xiao Ting , Zhong Weilong , Zhao Jianmin , Qian Baoxin , Liu Huijuan , Chen Shuang , Qiao Kailiang , Lei Yueyang , Zong Shumin , Wang Hongzhi , Liang Yuan , Zhang Heng , Meng Jing , Zhou Honggang , Sun Tao , Liu Yanrong , Yang Cheng
Published: September 2018

Vasculogenic mimicry (VM) is a functional microcirculation pattern formed by aggressive tumor cells and is related to the metastasis and poor prognosis of many cancer types, including hepatocellular carcinoma (HCC). Thus far, no effective drugs have been developed to target VM. In this study, patients with liver cancer exhibited reduced VM in tumor tissues after treatment with Rhizoma Paridis. Polyphyllin I (PPI), which is the main component of Rhizoma Paridis, inhibited VM formation in HCC lines and transplanted hepatocellular carcinoma cells. Molecular mechanism analysis showed that PPI impaired VM formation by blocking the PI3k-Akt-Twist1-VE-cadherin pathway. PPI also displayed dual effects on Twist1 by inhibiting the transcriptional activation of the Twist1 promoter and interfering with the ability of Twist1 to bind to the promoter of VE-cadherin, resulting in VM blocking. This study is the first to report on the clinical application of the VM inhibitor. Results may contribute to the development of novel anti-VM drugs in clinical therapeutics.
BH3 mimetics induce apoptosis independent of DRP-1 in melanoma
Authors: Mukherjee Nabanita , Strosnider Andrew , Vagher Bay , Lambert Karoline A. , Slaven Sarah , Robinson William A. , Amato Carol M. , Couts Kasey L. , Bemis Judson G. T. , Turner Jacqueline A. , Norris David A. , Shellman Yiqun G.
Published: September 2018

Despite the recent advancement in treating melanoma, options are still limited for patients without BRAF mutations or in relapse from current treatments. BH3 mimetics against members of the BCL-2 family have gained excitement with the recent success in hematological malignancies. However, single drug BH3 mimetic therapy in melanoma has limited effectiveness due to escape by the anti-apoptotic protein MCL-1 and/or survival of melanoma-initiating cells (MICs). We tested the efficacy of the BH3 mimetic combination of A-1210477 (an MCL-1 inhibitor) and ABT-263 (a BCL-2/BCL-XL/BCL-W inhibitor) in killing melanoma, especially MICs. We also sought to better define Dynamin-Related Protein 1 (DRP-1)’s role in melanoma; DRP-1 is known to interact with members of the BCL-2 family and is a possible therapeutic target for melanoma treatment. We used multiple assays (cell viability, apoptosis, bright field, immunoblot, and sphere formation), as well as the CRISPR/Cas9 genome-editing techniques. For clinical relevance, we employed patient samples of different mutation status, including some relapsed from current treatments such as anti-PD-1 immunotherapy. We found the BH3 mimetic combination kill both the MICs and non-MICs (bulk of melanoma) in all cell lines and patient samples irrespective of the mutation status or relapsed state (p < 0.05). Unexpectedly, the major pro-apoptotic proteins, NOXA and BIM, are not necessary for the combination-induced cell death. Furthermore, the combination impedes the activation of DRP-1, and inhibition of DRP-1 further enhances apoptosis (p < 0.05). DRP-1 effects in melanoma differ from those seen in other cancer cells. These results provide new insights into BCL-2 family’s regulation of the apoptotic pathway in melanoma, and suggest that inhibiting the major anti-apoptotic proteins is sufficient to induce cell death even without involvement from major pro-apoptotic proteins. Importantly, our study also indicates that DRP-1 inhibition is a promising adjuvant for BH3 mimetics in melanoma treatment.
Gravimetry through non-linear optomechanics
Authors: Qvarfort Sofia , Serafini Alessio , Barker P. F. , Bose Sougato
Published: September 2018

Precision gravimetry is key to a number of scientific and industrial applications, including climate change research, space exploration, geological surveys and fundamental investigations into the nature of gravity.  A variety of quantum systems, such as atom interferometry and on-chip-Bose–Einstein condensates have thus far been investigated to this aim. Here, we propose a new method which involves using a quantum optomechanical system for measurements of gravitational acceleration. As a proof-of-concept, we investigate the fundamental sensitivity for gravitational accelerometry of a cavity optomechanical system with a trilinear radiation pressure light-matter interaction. The phase of the optical output encodes the gravitational acceleration g and is the only component which needs to be measured. We prove analytically that homodyne detection is the optimal readout method and we predict an ideal fundamental sensitivity of Δg = 10−15 ms−2 for state-of-the-art parameters of optomechanical systems, showing that they could, in principle, surpass the best atomic interferometers even for low optical intensities. Further, we show that the scheme is strikingly robust to the initial thermal state of the oscillator.
Phosphoproteomic-based kinase profiling early in influenza virus infection identifies GRK2 as antiviral drug target
Authors: Yángüez Emilio , Hunziker Annika , Dobay Maria Pamela , Yildiz Soner , Schading Simon , Elshina Elizaveta , Karakus Umut , Gehrig Peter , Grossmann Jonas , Dijkman Ronald , Schmolke Mirco , Stertz Silke
Published: September 2018

Although annual influenza epidemics affect around 10% of the global population, current treatment options are limited and development of new antivirals is needed. Here, using quantitative phosphoproteomics, we reveal the unique phosphoproteome dynamics that occur in the host cell within minutes of influenza A virus (IAV) infection. We uncover cellular kinases required for the observed signaling pattern and find that inhibition of selected candidates, such as the G protein-coupled receptor kinase 2 (GRK2), leads to decreased IAV replication. As GRK2 has emerged as drug target in heart disease, we focus on its role in IAV infection and show that it is required for viral uncoating. Replication of seasonal and pandemic IAVs is severely decreased by specific GRK2 inhibitors in primary human airway cultures and in mice. Our study reveals the IAV-induced changes to the cellular phosphoproteome and identifies GRK2 as crucial node of the kinase network that enables IAV replication.
The Swr1 chromatin-remodeling complex prevents genome instability induced by replication fork progression defects
Authors: Srivatsan Anjana , Li Bin-Zhong , Szakal Barnabas , Branzei Dana , Putnam Christopher D. , Kolodner Richard D.
Published: September 2018

Genome instability is associated with tumorigenesis. Here, we identify a role for the histone Htz1, which is deposited by the Swr1 chromatin-remodeling complex (SWR-C), in preventing genome instability in the absence of the replication fork/replication checkpoint proteins Mrc1, Csm3, or Tof1. When combined with deletion of SWR1 or HTZ1, deletion of MRC1, CSM3, or TOF1 or a replication-defective mrc1 mutation causes synergistic increases in gross chromosomal rearrangement (GCR) rates, accumulation of a broad spectrum of GCRs, and hypersensitivity to replication stress. The double mutants have severe replication defects and accumulate aberrant replication intermediates. None of the individual mutations cause large increases in GCR rates; however, defects in MRC1, CSM3 or TOF1 cause activation of the DNA damage checkpoint and replication defects. We propose a model in which Htz1 deposition and retention in chromatin prevents transiently stalled replication forks that occur in mrc1, tof1, or csm3 mutants from being converted to DNA double-strand breaks that trigger genome instability.
Materials structure genealogy and high-throughput topological classification of surfaces and 2D materials
Authors: Himanen Lauri , Rinke Patrick , Foster Adam Stuart
Published: September 2018

Automated and verifiable structural classification for atomistic structures is becoming necessary to cope with the vast amount of information stored in various computational materials databases. Here we present a general recursive scheme for the structural classification of atomistic systems and introduce a structural materials map that can be used to organize the materials structure genealogy. We also introduce our implementation for the automatic classification of two-dimensional structures, especially focusing on surfaces and 2D materials. This classification procedure can automatically determine the dimensionality of a structure, further categorize the structure as a surface or a 2D material, return the underlying unit cell and also identify the outlier atoms, such as adsorbates. The classification scheme does not require explicit search patterns and works even in the presence of defects and dislocations. The classification is tested on a wide variety of atomistic structures and provides a high-accuracy determination for all of the returned structural properties. A software implementation of the classification algorithm is freely available with an open-source license.
Rapid detection of tetracycline resistance in bovine Pasteurella multocida isolates by MALDI Biotyper antibiotic susceptibility test rapid assay (MBT-ASTRA)
Authors: Van Driessche Laura , Bokma Jade , Gille Linde , Ceyssens Pieter-Jan , Sparbier Katrin , Haesebrouck Freddy , Deprez Piet , Boyen Filip , Pardon Bart
Published: September 2018

Pasteurella multocida is notorious for its role as an opportunistic pathogen in infectious bronchopneumonia, the economically most important disease facing cattle industry and leading indication for antimicrobial therapy. To rationalize antimicrobial use, avoiding imprudent use of highly and critically important antimicrobials for human medicine, availability of a rapid antimicrobial susceptibility test is crucial. The objective of the present study was to design a MALDI Biotyper antibiotic susceptibility test rapid assay (MBT-ASTRA) procedure for tetracycline resistance detection in P. multocida. This procedure was validated on 100 clinical isolates with MIC-gradient strip test, and a comparison with disk diffusion was made. Sensitivity and specificity of the MBT-ASTRA procedure were 95.7% (95% confidence interval (CI) = 89.8–101.5) and 100% (95% CI = 100–100), respectively, classifying 98% of the isolates correctly after only three hours of incubation. Sensitivity and specificity of disk diffusion were 93.5% (95% CI = 86.3–100.6) and 96.3% (95% CI = 91.3–101.3) respectively, classifying 95% of the isolates correctly. In conclusion, this MBT-ASTRA procedure has all the potential to fulfil the need for a rapid and highly accurate tetracycline susceptibility testing in P. multocida to rationalize antimicrobial use in outbreaks of bronchopneumonia in cattle or other clinical presentations across species.
Interannual variability of leaf area index of an evergreen conifer stand was affected by carry-over effects from recent climate conditions
Authors: Sumida Akihiro , Watanabe Tsutomu , Miyaura Tomiyasu
Published: September 2018

Despite the relevance of leaf area index (LAI) to forest productivity, few studies have focused on the interannual variability of LAI of an evergreen stand and its relationship with stand growth and meteorological factors. We estimated the change in LAI of an evergreen conifer (Chamaecyparis obtusa) stand over 19 years from a dataset using allometric methods. The LAI varied between 7.1 and 8.8 m2 m−2, with a 95% confidence interval of <1.1 m2 m−2over the 19 years. This LAI range was maintained such that the gradual increase in leaf area (LA) of the largest trees counterbalanced the gradual loss in LA of the smallest trees. Meanwhile, more trees showed a temporary decrease in LA in years with low summer precipitation. The LAI and current-year mean temperature for July and August (TJA) were weakly correlated, whereas the correlation coefficient increased (r = 0.93) when LAI was correlated with the moving averageTJAover the previous 6 years, which agreed with the estimated turnover time of canopy foliage. The annual stem biomass growth rate was significantly positively correlated with summer precipitation, but not with LAI. These results will be useful for refining models in studies on forest growth and global climate change.
Neurotransmitter identity and electrophysiological phenotype are genetically coupled in midbrain dopaminergic neurons
Authors: Tapia Mónica , Baudot Pierre , Formisano-Tréziny Christine , Dufour Martial A. , Temporal Simone , Lasserre Manon , Marquèze-Pouey Béatrice , Gabert Jean , Kobayashi Kazuto , Goaillard Jean-Marc
Published: September 2018

Most neuronal types have a well-identified electrical phenotype. It is now admitted that a same phenotype can be produced using multiple biophysical solutions defined by ion channel expression levels. This argues that systems-level approaches are necessary to understand electrical phenotype genesis and stability. Midbrain dopaminergic (DA) neurons, although quite heterogeneous, exhibit a characteristic electrical phenotype. However, the quantitative genetic principles underlying this conserved phenotype remain unknown. Here we investigated the quantitative relationships between ion channels’ gene expression levels in midbrain DA neurons using single-cell microfluidic qPCR. Using multivariate mutual information analysis to decipher high-dimensional statistical dependences, we unravel co-varying gene modules that link neurotransmitter identity and electrical phenotype. We also identify new segregating gene modules underlying the diversity of this neuronal population. We propose that the newly identified genetic coupling between neurotransmitter identity and ion channels may play a homeostatic role in maintaining the electrophysiological phenotype of midbrain DA neurons.
ADAP1 limits neonatal cardiomyocyte hypertrophy by reducing integrin cell surface expression
Authors: Giguère Hugo , Dumont Audrey-Ann , Berthiaume Jonathan , Oliveira Vanessa , Laberge Gino , Auger-Messier Mannix
Published: September 2018

The ArfGAP with dual PH domains 1 (ADAP1) regulates the activation of the hypertrophic mitogen-activated protein kinase ERK1/2 pathway in non-cardiomyocytes. However, its role in cardiomyocytes is unknown. Our aim was to characterize the role of ADAP1 in the hypertrophic process of cardiomyocytes. We assessed the expression of ADAP1 in the hearts of adult and neonatal rats by RT-qPCR and Western blotting and showed that it is preferentially expressed in cardiomyocytes. Adenoviral-mediated ADAP1 overexpression in cultured rat neonatal ventricular cardiomyocytes limited their serum-induced hypertrophic response as measured by immunofluorescence microscopy. Furthermore, ADAP1 overexpression completely blocked phenylephrine- and Mek1 constitutively active (Mek1ca) mutant-induced hypertrophy in these cells. The anti-hypertrophic effect of ADAP1 was not caused by a reduction in protein synthesis, interference with the Erk1/2 pathway, or disruption of the fetal gene program activation, as assessed by nascent protein labeling, Western blotting, and RT-qPCR, respectively. An analysis of cultured cardiomyocytes by confocal microscopy revealed that ADAP1 partially re-organizes α-actinin into dense puncta, a phenomenon that is synergized by Mek1ca overexpression. Biotin labeling of cell surface proteins from cardiomyocytes overexpressing ADAP1 revealed that it reduces the surface expression of β1-integrin, an effect that is strongly potentiated by Mek1ca overexpression. Our findings provide insights into the anti-hypertrophic function of ADAP1 in cardiomyocytes.
Raman imaging as a new approach to identification of the mayenite group minerals
Authors: Środek D. , Dulski M. , Galuskina I.
Published: September 2018

The mayenite group includes minerals with common formula Ca12Al14O32−x(OH)3x[W6−3x], where W = F, Cl, OH, H2O and x = 0–2. This distinction in the composition is associated with W site which may remain unoccupied or be occupied by negatively charged ions: OH−, F−, Cl−, as well as neutral molecules like H2O. However, there is no experimental approach to easily detect or differentiate mineral species within the mayenite group. Electron micro-beam facilities with energy- or wavelength-dispersive X-ray detectors, as most common tools in mineralogy, appear to be insufficient and do not provide a definite identification, especially, of hydroxylated or hydrated phases. Some solution provides typical Raman analysis ensuring identification of minerals and 3D Raman imaging as an innovative approach to distinguish various co-existing minerals of the mayenite group within a small area of the rock sample. Raman spectroscopy has also been successfully used for a determination of water type incorporated into the mineral structure as well as for a spatial distribution of phases by cluster approach analysis and/or integrated intensity analysis of bands in the hydroxyl region. In this study, Raman technique was for the first time used to reconstruct a 3D model of mayenite group mineral zonation, as well as to determine a way of water incorporation in the structure of these minerals. Moreover, for the first time, Raman data were correlated with alterations during the mineral-forming processes and used for reconstruction of the thermal history of studied rock. As a result, the influence of combustion gases has been proposed as a crucial factor responsible for the transformation between fluormayenite and fluorkyuygenite.
Casein Kinase 1 Epsilon Regulates Glioblastoma Cell Survival
Authors: Varghese Robin T. , Young Sarah , Pham Lily , Liang Yanping , Pridham Kevin J. , Guo Sujuan , Murphy Susan , Kelly Deborah F. , Sheng Zhi
Published: September 2018

Glioblastoma is the most common malignant brain cancer with a dismal prognosis. The difficulty in treating glioblastoma is largely attributed to the lack of effective therapeutic targets. In our previous work, we identified casein kinase 1 ε (CK1ε, also known as CSNK1E) as a potential survival factor in glioblastoma. However, how CK1ε controls cell survival remains elusive and whether targeting CK1ε is a possible treatment for glioblastoma requires further investigation. Here we report that CK1ε was expressed at the highest level among six CK1 isoforms in glioblastoma and enriched in high-grade glioma, but not glia cells. Depletion of CK1ε remarkably inhibited the growth of glioblastoma cells and suppressed self-renewal of glioblastoma stem cells, while having limited effect on astrocytes. CK1ε deprivation activated β-catenin and induced apoptosis, which was further counteracted by knockdown of β-catenin. The CK1ε inhibitor IC261, but not PF-4800567, activated β-catenin and blocked the growth of glioblastoma cells and glioblastoma stem cells. Congruently, IC261 elicited a robust growth inhibition of human glioblastoma xenografts in mice. Together, our results demonstrate that CK1ε regulates the survival of glioblastoma cells and glioblastoma stem cells through β-catenin signaling, underscoring the importance of targeting CK1ε as an effective treatment for glioblastoma.
Independent adaptation mechanisms for numerosity and size perception provide evidence against a common sense of magnitude
Authors: Anobile Giovanni , Burr David C. , Iaia Marika , Marinelli Chiara V. , Angelelli Paola , Turi Marco
Published: September 2018

How numerical quantity is processed is a central issue for cognition. On the one hand the “number sense theory” claims that numerosity is perceived directly, and may represent an early precursor for acquisition of mathematical skills. On the other, the “theory of magnitude” notes that numerosity correlates with many continuous properties such as size and density, and may therefore not exist as an independent feature, but be part of a more general system of magnitude. In this study we examined interactions in sensitivity between numerosity and size perception. In a group of children, we measured psychophysically two sensory parameters: perceptual adaptation and discrimination thresholds for both size and numerosity. Neither discrimination thresholds nor adaptation strength for numerosity and size correlated across participants. This clear lack of correlation (confirmed by Bayesian analyses) suggests that numerosity and size interference effects are unlikely to reflect a shared sensory representation. We suggest these small interference effects may rather result from top-down phenomena occurring at late decisional levels rather than a primary “sense of magnitude”.
Cardiac magnetic resonance using late gadolinium enhancement and atrial T1 mapping predicts poor outcome in patients with atrial fibrillation after catheter ablation therapy
Authors: Luetkens Julian A. , Wolpers Anne C. , Beiert Thomas , Kuetting Daniel , Dabir Darius , Homsi Rami , Meendermann Hendrik , Dayé Natalie Abou , Knappe Vincent , Karsdal Morten , Nielsen Signe H. , Genovese Federica , Stöckigt Florian , Linhart Markus , Thomas Daniel , Nickenig Georg , Schild Hans H. , Schrickel Jan W. , Andrié René P.
Published: September 2018

To determine the pre-procedural value of different fibrotic biomarkers and comprehensive cardiac magnetic resonance (CMR) for the prediction of poor response to ablation therapy in patients with atrial fibrillation (AF). Left atrial (LA) late gadolinium enhancement (LGE) and native LA T1 relaxation times were assessed using CMR. Plasma levels of relaxin, myeloperoxidase and serum levels of matrix metalloproteinase (MMP)-mediated cardiac specific titin fragmentation and MMP-mediated type IV collagen degradation were obtained. Poor outcome was defined by the recurrence of AF during 1-year follow-up. 61 patients were included in final analysis. Twenty (32.8%) patients had recurrence of AF. Patients with a recurrence of AF had a higher percentage of LA LGE (26.7 ± 12.5% vs. 17.0 ± 7.7%; P < 0.001), higher LA T1 relaxation times (856.7 ± 112.2 ms vs. 746.8 ± 91.0 ms; P < 0.001) and higher plasma levels of relaxin (0.69 ± 1.34 pg/ml vs. 0.37 ± 0.88 pg/ml; P = 0.035). In the multivariate Cox regression analysis, poor ablation outcome was best predicted by advanced LGE stage (hazard ratio (HR):5.487; P = 0.001) and T1 relaxation times (HR:1.007; P = 0.001). Pre-procedural CMR is a valuable tool for prediction of poor response to catheter ablation therapy in patients with AF. It offers various imaging techniques for outcome prediction and might be valuable for a better patient selection prior to ablation therapy.
Accretionary prism collapse: a new hypothesis on the source of the 1771 giant tsunami in the Ryukyu Arc, SW Japan
Authors: Okamura Yukinobu , Nishizawa Azusa , Fujii Yushiro , Yanagisawa Hideaki
Published: September 2018

The giant 1771 Yaeyama tsunami occurred in the southwestern part of the Ryukyu Arc, a region on an obliquely subducting plate boundary, which shows no direct evidence of inter-plate coupling. Studies of tsunami boulders and deposits suggest that the recurrence interval of comparably giant tsunamis is roughly 500 to 1000 years. Tsunami source models, which include either slip on a shallow plate boundary or active faulting plus a landslide on the overriding plate, are controversial because of inconsistencies in the geophysical and geological data. We discovered a seafloor depression that is approximately 30 km wide and 80 km long extending in the ESE-WNW direction. This depression is accompanied by a seaward bulge on the accretionary prism along the Ryukyu Trench, which is based on detailed bathymetric data and interpreted to be the result of accretionary prism collapse and seaward displacement by rotational slide. A simple tsunami simulation shows that the slide is a plausible source of the 1771 tsunami. We propose a collapse model, in which the accretionary prism remained over-steepened as strike-slip faulting removed the prism toe. Our model indicates that some oblique subduction zones are capable of generating giant tsunamis regardless of weak or strong coupling.
Investigation of hindbrain activity during active locomotion reveals inhibitory neurons involved in sensorimotor processing
Authors: Severi Kristen E. , Böhm Urs L. , Wyart Claire
Published: September 2018

Locomotion in vertebrates relies on motor circuits in the spinal cord receiving inputs from the hindbrain to execute motor commands while dynamically integrating proprioceptive sensory feedback. The spatial organization of the neuronal networks driving locomotion in the hindbrain and role of inhibition has not been extensively investigated. Here, we mapped neuronal activity with single-cell resolution in the hindbrain of restrained transgenic Tg(HuC:GCaMP5G) zebrafish larvae swimming in response to whole-field visual motion. We combined large-scale population calcium imaging in the hindbrain with simultaneous high-speed recording of the moving tail in animals where specific markers label glycinergic inhibitory neurons. We identified cells whose activity preferentially correlates with the visual stimulus or motor activity and used brain registration to compare data across individual larvae. We then morphed calcium imaging data onto the zebrafish brain atlas to compare with known transgenic markers. We report cells localized in the cerebellum whose activity is shut off by the onset of the visual stimulus, suggesting these cells may be constitutively active and silenced during sensorimotor processing. Finally, we discover that the activity of a medial stripe of glycinergic neurons in the domain of expression of the transcription factor engrailed1b is highly correlated with the onset of locomotion. Our efforts provide a high-resolution, open-access dataset for the community by comparing our functional map of the hindbrain to existing open-access atlases and enabling further investigation of this population’s role in locomotion.
Emerging role of precision medicine in biliary tract cancers
Authors: Bogenberger James M. , DeLeon Thomas T. , Arora Mansi , Ahn Daniel H. , Borad Mitesh J.
Published: September 2018

Biliary tracts cancers (BTCs) are a diverse group of aggressive malignancies with an overall poor prognosis. Genomic characterization has uncovered many putative clinically actionable aberrations that can also facilitate the prognostication of patients. As such, comprehensive genomic profiling is playing a growing role in the clinical management of BTCs. Currently however, there is only one precision medicine approved by the US Food and Drug Administration (FDA) for the treatment of BTCs. Herein, we highlight the prevalence and prognostic, diagnostic, and predictive significance of recurrent mutations and other genomic aberrations with current clinical implications or emerging relevance to clinical practice. Some ongoing clinical trials, as well as future areas of exploration for precision oncology in BTCs are highlighted.
Pushing the frontiers: boron-11 NMR as a method for quantitative boron analysis and its application to determine boric acid in commercial biocides
Authors: Aguilera-Sáez Luis Manuel , Belmonte-Sánchez José Raúl , Romero-González Roberto , Martínez Vidal José Luis , Arrebola Francisco Javier , Garrido Frenich Antonia , Fernández Ignacio
Published: September 2018

We present herein the application of a qNMR method that employs for the first time a quadrupolar nucleus such as boron-11 in commercial biocides.
Identifying the acceptor state in NiO hole collection layers: direct observation of exciton dissociation and interfacial hole transfer across a Fe2O3/NiO heterojunction
Authors: Biswas Somnath , Husek Jakub , Londo Stephen , Fugate Elizabeth A. , Baker L. Robert
Published: September 2018

Ultrafast XUV reflection–absorption identifies interfacial charge transfer mechanism and the hole acceptor state in a Fe2O3/NiO model heterojunction
Homochiral coordination polymers constructed from V-shaped oxybisbenzoyl-based amino acid derivatives: structures, magnetic and photoluminescence properties
Authors: Guan Guo-Xiu , Guo Wei-Xiao , Liu Xu , Yue Qi , Gao En-Qing
Published: September 2018

Five novel amino acid-modified HCPs have been prepared using the V-shaped semi-rigid 4,4′-oxybis(benzoic acid) instead of usual rigid polycarboxylate units.
Conformational twisting of a formate-bridged diiridium complex enables catalytic formic acid dehydrogenation
Authors: Lauridsen Paul J. , Lu Zhiyao , Celaje Jeff J. A. , Kedzie Elyse A. , Williams Travis J.
Published: September 2018

Catalytic reactivity is switched on for formic acid dehydrogenation by a single precursor's unique ability to form a geometrically twisted dimer.
Polarization-based super-resolution imaging of surface-enhanced Raman scattering nanoparticles with orientational information
Authors: Wang Miaoyan , Chen Min , Zhanghao Karl , Zhang Xu , Jing Zhenli , Gao Juntao , Zhang Michael Q. , Jin Dayong , Dai Zhifei , Xi Peng , Dai Qionghai
Published: September 2018

Super-resolution imaging and orientation detection of surface enhanced Raman scattering nanoparticles using polarization modulation.
Bi2Se3 nanoplates for contrast-enhanced photoacoustic imaging at 1064 nm
Authors: Park Sara , Park Gyeongbae , Kim Jeesu , Choi Wonseok , Jeong Unyong , Kim Chulhong
Published: September 2018

Bi2Se3 nanoplates can be a promising PA contrast agent at 1064 nm that offers a high optical absorbance in the second NIR region providing a high contrast imaging and increased depth of penetration.
MOF–cation exchange resin composites and their use for water decontamination
Authors: He Ping , Haw Kok-Giap , Ren Jiawang , Fang Qianrong , Qiu Shilun , Valtchev Valentin
Published: September 2018

Cation exchange resin–ZIF-8 composite beads were prepared and used for the decontamination of water from dye and medical pollutants.
Mass production of Mn2+-doped CsPbCl3 perovskite nanocrystals with high quality and enhanced optical performance
Authors: Liu Wenna , Zheng Jinju , Cao Sheng , Wang Lin , Gao Fengmei , Chou Kuo-Chih , Hou Xinmei , Yang Weiyou
Published: September 2018

A novel microwave-assisted hot injection strategy for mass production of high quality Mn2+:CsPbCl3 NCs was reported.
Atomic-scale investigation of MgO growth on fused quartz using angle-dependent NEXAFS measurements
Authors: Singh Jitendra Pal , Kim So Hee , Won Sung Ok , Lee Ik-Jae , Chae Keun Hwa
Published: September 2018

Near edge X-ray absorption fine structure measurements reveal the formation of MgO on fused quartz substrate.
Twist sense control in terminally functionalized ortho-phenylenes
Authors: Vemuri Gopi Nath , Pandian Rathiesh R. , Spinello Brian J. , Stopler Erika B. , Kinney Zacharias J. , Hartley C. Scott
Published: September 2018

Chiral groups induce opposite twist senses of o-phenylene helices depending on their positions in dynamic mixtures.
TSC1 deletion in fibroblasts alleviates lipopolysaccharide-induced acute kidney injury
Authors: Shen Junhui , Cui Zhong-Kai , Yao Fang , Li Kai , Zhang Yue , Chen Zhenguo , Zhou Yuxia , Xu Song , Zhang Yuwei , Jiang Wenqing , Zhang Hanbin , Tan Kaifen , Liu Anling , Bai Xiaochun
Published: September 2018

Mechanistic target of rapamycin complex 1 (mTORC1) signaling is active in inflammation, but its involvement in septic acute kidney injury (AKI) has not been shown. mTORC1 activation (p-S6) in renal fibroblasts was increased in a mouse AKI model induced by 1.5 mg/kg lipopolysaccharide (LPS). Deletion of tuberous sclerosis complex 1 (TSC1), an mTORC1 negative regulator, in fibroblasts (Fibro-TSC1−/−) inhibited the elevation of serum creatinine and blood urea nitrogen in AKI compared with that in TSC1fl/fl control mice. Endothelin-1 (EDN1) and phospho-Jun-amino-terminal kinase (p-JNK) were up-regulated in Fibro-TSC1−/− renal fibroblasts after LPS challenge. Rapamycin, an mTORC1 inhibitor, and bosentan, an EDN1 antagonist, eliminated the difference in renal function between TSC1fl/fl and Fibro-TSC1−/− mice after LPS injection. Rapamycin restored LPS-induced up-regulation of EDN1, endothelin converting enzyme-1 (ECE1), and p-JNK in TSC1-knockdown mouse embryonic fibroblasts (MEFs). SP600125, a Jun-amino-terminal kinase (JNK) inhibitor, attenuated LPS-induced enhancement of EDN1 and ECE1 in TSC1-knockdown MEFs without a change in phospho-S6 ribosomal protein (p-S6) level. The results indicate that mTORC1–JNK-dependent up-regulation of ECE1 elevated EDN1 in TSC1-knockout renal fibroblasts and contributed to improvement of renal function in Fibro-TSC1−/− mice with LPS-induced AKI. Renal fibroblast mTORC1 plays an important role in septic AKI.
Platelet communication with the vascular wall: role of platelet-derived microparticles and non-coding RNAs
Authors: Randriamboavonjy Voahanginirina , Fleming Ingrid
Published: September 2018

Platelets play an important role in vascular homeostasis through their interaction with circulating blood cells as well as the vascular wall. Platelet-mediated communication with other cells can take the form of direct cell–cell interactions via membrane receptors or indirectly through the release of different soluble factors stored in their granules as well as through the release of microparticles. The latter carry different proteins and RNAs which are transferred to the target cells. The aim of this review is to discuss the role of platelet-derived factors, adhesion molecules as well as RNAs as mediators of the cross-talk between platelets and the vessel wall.
Field and laboratory trials of 400GBASE‐LR8 over fibre distances up to 35 km
Authors: Zhou Y.R. , Smith K. , Gilson M. , Brooks P. , Cole C. , Yu C.
Published: September 2018

Successful experimental demonstration and field trial of 400GBASE‐LR8 is reported based on 4‐level pulse amplitude modulation format over standard G.652 single‐mode fibre using CFP8 pluggable optical transceivers. Stable long‐term error‐free performance of 400GBASE‐LR8 optical signal over fibre spools of varying lengths up to 35 km is demonstrated, which is significantly longer than the IEEE standard 802.3bs specification of 10 km reach. For the first time, error‐free full throughput performance of 400GBASE‐LR8 over a 27 km field fibre link including optical patch panels through operational exchanges is also demonstrated. The results demonstrate that this early 400GBASE‐LR8 client technology is suitable for practical network deployment scenarios and has potential for even longer reach beyond the 10 km specification.
Discriminatively learned network for i‐vector based speaker recognition
Authors: Yao Shengyu , Zhou Ruohua , Zhang Pengyuan , Yan Yonghong
Published: September 2018

In many i‐vector based speaker recognition frameworks, the key challenge is to develop effective channel compensation methods for enlarging inter‐class differences while reducing intra‐class variations. This challenge is handled with a discriminatively learned network (DLN), which uses both speaker classification and verification signals as supervision. The speaker classification task forces the embeddings (vectors mapped from i‐vectors) of different identities drawing apart to increase the inter‐class variation, while the verification task pulls the embeddings of the same identity together to reduce the intra‐class variation. DLN projects i‐vectors to a more discriminative embedding space. However, the verification scores are cosine similarities between these embeddings. The learned DLN can be well generalised to new speakers unseen in the training data. On the text‐dependent challenging Robust Speaker Recognition (RSR2015) database, the performance is significantly improved when compared with the linear discriminant analysis (LDA) and Gaussian probabilistic LDAmethods.
Augmenting Microsoft's HoloLens with vuforia tracking for neuronavigation
Authors: Frantz Taylor , Jansen Bart , Duerinck Johnny , Vandemeulebroucke Jef
Published: September 2018

Major hurdles for Microsoft's HoloLens as a tool in medicine have been accessing tracking data, as well as a relatively high‐localisation error of the displayed information; cumulatively resulting in its limited use and minimal quantification. The following work investigates the augmentation of HoloLens with the proprietary image processing SDK Vuforia, allowing integration of data from its front‐facing RGB camera to provide more spatially stable holograms for neuronavigational use. Continuous camera tracking was able to maintain hologram registration with a mean perceived drift of 1.41 mm, as well as a mean sub 2‐mm surface point localisation accuracy of 53%, all while allowing the researcher to walk about a test area. This represents a 68% improvement for the later and a 34% improvement for the former compared with a typical HoloLens deployment used as a control. Both represent a significant improvement on hologram stability given the current state‐of‐the‐art, and to the best of the authors knowledge are the first example of quantified measurements when augmenting hologram stability using data from the RGB sensor.
Power flow control scheme for multiport power electronics transformers
Authors: Zhang Huaitian , Jing Long , Wu Xuezhi , Jiang Jiuchun , Wickramasinghe Harith R. , Konstantinou Georgios
Published: September 2018

Development of power electronics transformers (PETs) has made dc distribution and hybrid ac/dc systems a competitive solution for future network expansion. This study focuses on the functions of a multiport PET interfacing medium‐voltage and low‐voltage networks. A comprehensive power flow control scheme based on a globalised multiport transmission model of the PET and droop control is derived. This allows for a coordinated energy exchange between the ports of the PET, which enables autonomous operation. Simulations of the proposed approach in a hybrid ac/dc distribution network with different levels of distributed generation and loads verify the effectiveness of the method.
Overshoot and settling time assignment with PID for first‐order and second‐order systems
Authors: Nguyen Nam Hoai , Nguyen Phuoc Doan
Published: September 2018

Many methods have been proposed to design proportional–integral–derivative (PID) controllers for various classes of linear systems. However, there has not yet been any method that deals concurrently with assignments of both overshoot and settling time of closed‐loop systems. In this study, a PID controller design method is proposed to achieve both desired overshoot and expected settling time at the same time for certain classes of linear systems. Some examples are given to illustrate the proposed method and compare it with the other existing methods in terms of performance. The obtained results from the examples are based on simulation.
Stability of fractional‐order nonlinear systems by Lyapunov direct method
Authors: Tuan Hoang T. , Trinh Hieu
Published: September 2018

In this study, by using a characterisation of functions having a fractional derivative, the authors propose a rigorous fractional Lyapunov function candidate method to analyse the stability of fractional‐order nonlinear systems. First, they prove an inequality concerning the fractional derivatives of convex Lyapunov functions without the assumption of the existence of the derivative of pseudo‐states. Second, they establish fractional Lyapunov functions to fractional‐order systems without the assumption of the global existence of solutions. Their theorems fill the gaps and strengthen results in some existing papers.
Split ratio optimisation of high‐speed permanent magnet brushless machines considering mechanical constraints
Authors: Feng Jianghua , Wang Yu , Guo Shuying , Chen Zhichu , Wang Yu , Zhu Zi‐Qiang
Published: September 2018

The split ratio of rotor outer diameter to stator outer diameter is one of the most important design parameters due to its significant impact on machine torque density and efficiency. It has been optimised analytically in existing papers with due account given only for the thermal limitations. Here, the optimised split ratio for high‐speed permanent magnet machines (HSPMM) with consideration of the mechanical constraints is investigated analytically. In addition, the influences of flux density ratio, maximum operating speed and sleeve material on the optimised split ratio are discussed in detail. The analytical results are verified by finite‐element analyses. It is demonstrated that the optimised split ratio as well as the achievable torque of HSPMM is significantly reduced when the mechanical constraints are taken into consideration. The experimental results on a 6/slot‐4pole HSPMM confirm the validity of previous analyses.
Optimal flux‐weakening control of a new five‐phase FT‐IPM motor based on DTC and SVPWM for electric vehicle applications
Authors: Zhang Li , Zhu Xiaoyong , Fan Ying , Li Chenxue
Published: September 2018

This study proposes two flux‐weakening control strategies for a new five‐phase fault‐tolerant interior‐permanent‐magnet (FT‐IPM) motor, in which direct torque flux‐weakening control (DTFWC) and space vector pulse width modulation (SVPWM)‐based vector flux‐weakening control (SVMFWC) are adopted. To achieve the reduced computation and the good operating performance such as minimised copper loss, improved dynamic response performance, and constant power operation in FW region, the multi‐objective optimisation without complex non‐linear optimisation algorithms for the DTFWC and SVMFWC are developed. In addition, the two proposed strategies have the same control objective but realised with two different ways. The reducing copper loss is obtained in DTFWC by reducing flux‐weakening current with the full utilisation of DC‐link voltage, while the reducing copper loss is gained in SVMFWC by decreasing the required current amplitude with maximum output torque per ampere current. Furthermore, the effectiveness of the proposed DTFWC and SVMFWC strategies is verified by simulation and experimental results.
Scene invariant crowd counting using multi‐scales head detection in video surveillance
Authors: Ma Tianjun , Ji Qingge , Li Ning
Published: September 2018

With a soaring increase in the application of video surveillance in daily life, the estimation of crowd density has already become a hot field. Crowd counting has a very close relationship with traffic planning, pedestrian analysing and emergency warning. Here, a novel crowd counting method based on multi‐scales head detection is proposed. The authors’ approach first uses gradients difference to extract the foreground of the images and apply the overlapped patches in different scales to split the input images. Then, the patches are selected and classified into different groups corresponding to their gradient distributions, and features are extracted for training. Finally, with the predicting result, density maps of different scales are computed and summed with the perspective map. In particular, the authors’ method overcomes the traditional detecting method's deficiencies of low accuracy when facing perspective transformation. Also, experiments demonstrate that this proposed method not only achieved high accuracy in counting but also has outstanding robustness in our data sets.
Time/frequency domain modelling for grid‐connected MMC sub‐synchronous/super‐synchronous oscillation in PV MVDC power collection and integration system
Authors: Wang Jianhua , Gao Shang , Ji Zhendong , Sun Yichao , Hong Lucheng , Luo Fangfang , Gu Wei
Published: September 2018

This study proposes a comprehensive PWM‐based modular multilevel converter (MMC) model in both time and frequency domain at the same time. The time‐domain model not only accelerates simulation speed but also describe the characteristics of sub‐modules, such as the dynamic voltage‐balancing process of sub‐module capacitors. The frequency‐domain model provides the output impedance of the grid‐connected MMC inverter in positive‐sequence and negative‐sequence coordinates. The proposed model, validated by results of different scenarios listed, at last, predicts and eliminates sub‐synchronous/super‐synchronous oscillations with impedance shaping method.