bluuebunny/crossref_metadata_2025 huggingface dataset:
Parental conflicts and materialism in adolescents: Emotional insecurity as a mediator
Authors: Ching Boby Ho‐Hong , Wu Xiaohan
Published: November 2018

Introduction

This longitudinal study investigated whether and how parental conflicts contributed to adolescents' endorsement of materialistic values.

Method

Two hundred and fourteen Chinese adolescents in Hong Kong (102 boys; mean age = 16.52 years) completed a set of questionnaires including materialism, emotional insecurity, parental conflict behaviour, and perceptions of parents (warmth, autonomy, and involvement).

Results

Consistent with the psychological insecurity hypothesis and the emotional security theory, emotional insecurity mediated the connection between parental conflict behaviour and adolescents' materialism. Adolescents who had their parents dealing with their conflicts in destructive ways reported higher levels of emotional insecurity, which was in turn associated with higher levels of materialism. By contrast, adolescents who had their parents dealing with their conflicts constructively reported lower levels of emotional insecurity, which was linked to lower levels of materialism.

Conclusion

Parental conflict behaviour contributes to adolescents' materialism through its influence on emotional insecurity.
Development and Evaluation of a Competency-Based Anatomy Rotation for Diagnostic Radiology Residents during Internship Year: A Canadian Experience
Authors: Darras Kathryn E. , Spouge Rebecca , de Bruin Anique , Hu Jeff , Guest Will , Mar Colin , Hatala Rose , Hague Cameron , Forster Bruce B. , Chang Silvia D.
Published: November 2018

Rationale and Aim

As medical schools reduce the hours of anatomy teaching, residents in anatomy-intensive residency programs like radiology must independently acquire the anatomy knowledge needed to achieve competency. The purpose of this study was to develop and evaluate a 4-week competency-based self-directed anatomy rotation for junior residents.

Methods

Seven post-graduate year 1 (PGY-1) radiology residents completed a 4-week rotation of radiologic anatomy. The objectives were developed from standards, senior residents, and expert opinion, and the competency-based curriculum included self-directed modules. Pre-course and post-course tests were administered and test scores were compared using an unpaired t test. In addition, PGY-1 residents completed a course evaluation and survey regarding their anatomy knowledge and anatomy exposure prior to completing the course.

Results

Out of the 25 points available, the average pre-test score was 10.79 ± 2.78 (range 8–16.5), and the average post-test score was 21.64 ± 2.23 (range 18.5–25). This difference was statistically significant ( P < .0001). The PGY-1 residents reported receiving < 10% of dedicated radiologic anatomy teaching prior to residency and felt unprepared for the anatomy required in residency. Overall, residents felt more confident in looking at images after completing the self-directed radiologic anatomy course.

Conclusion

This study demonstrates the feasibility of creating a self-directed course for radiology residents that significant improves their anatomy knowledge. Given the trend in medical undergraduate education away from dedicated anatomy teaching, residency programs should consider addressing anatomy education more formally for junior residents to ensure that trainees receive the foundational knowledge required for residency.
Essentials on Oncological Imaging: Postoperative Computed Tomography and Magnetic Resonance Imaging of Oral Tongue Cancer
Authors: Baba Akira , Ojiri Hiroya , Ikeda Koshi , Yamauchi Hideomi , Ogino Nobuhiro , Seto Yuki , Kobashi Yuko , Yamazoe Shinji , Mogami Takuji
Published: November 2018

The contribution of diagnostic imaging in evaluating the pre- and postoperative status of tongue cancer is essential. Interpretation of postoperative images is made difficult by deformation; therefore, it is necessary to know how surgical technique, biological reaction, postoperative anatomy, and local recurrence are reflected on the images. This study explains the postoperative imaging features of tongue cancer to help in the early detection of local recurrence and avoid inappropriate treatment. We review schematic drawings of representative surgical procedures for tongue carcinoma, variable radiological features in postoperative conditions with or without complications, and typical features of local failures and their mimics. This article clarifies the important tasks of radiologists and clinicians in the postoperative evaluation of tongue carcinoma.
Girl Scouts Can Now Earn Space Science Badges
Authors: Cartier Kimberly
Published: November 2018

Young Girl Scouts can be explorers, adventurers, and investigators as they work toward badges that teach them about the Sun, the solar system, and the stars.
Bruning Receives 2018 Atmospheric and Space Electricity Early Career Award
Authors:   AGU
Published: November 2018

Eric C. Bruning will receive the 2018 Atmospheric and Space Electricity Early Career Award at AGU’s Fall Meeting 2018, to be held 10–14 December in Washington, D. C. The award recognizes “outstanding early career contributions to atmospheric and space electricity.”
Free Flight Time for Projects in Atmospheric Sciences
Authors: Bedford Bailey
Published: November 2018

Got an urgent or innovative project that involves collecting airborne data? A research flight company is donating an estimated $100,000 of its resources to help you.
Blind Signal Separation Methods for InSAR: The Potential to Automatically Detect and Monitor Signals of Volcanic Deformation
Authors: Gaddes M. E. , Hooper A. , Bagnardi M. , Inman H. , Albino F.
Published: November 2018

There are some 1,500 volcanoes with the potential to erupt, but most are not instrumentally monitored. However, routine acquisition by the Sentinel‐1 satellites now fulfils the requirements needed for interferometric synthetic aperture radar (InSAR) to progress from a retrospective analysis tool to one used for near‐real‐time monitoring globally. However, global monitoring produces vast quantities of data, and consequently, an automatic detection algorithm is therefore required that is able to identify signs of new deformation, or changes in rate, in a time series of interferograms. On the basis that much of the signal contained in a time series of interferograms can be considered as a linear mixture of several latent sources, we explore the use of blind source separation methods to address this issue. We consider principal component analysis and independent component analysis (ICA) which have previously been applied to InSAR data and nonnegative matrix factorization which has not. Our systematic analysis of the three methods shows ICA to be best suited for most applications with InSAR data. However, care must be taken in the dimension reduction step of ICA not to remove important smaller magnitude signals. We apply ICA to the 2015 Wolf Volcano eruption (Galapagos Archipelago, Ecuador) and automatically isolate three signals, which are broadly similar to those manually identified in other studies. Finally, we develop a prototype detection algorithm based on ICA to identify the onset of the eruption.
Ion Escape From Mars Through Time: An Extrapolation of Atmospheric Loss Based on 10 Years of Mars Express Measurements
Authors: Ramstad Robin , Barabash Stas , Futaana Yoshifumi , Nilsson Hans , Holmström Mats
Published: November 2018

Solar wind‐driven atmospheric ion escape has long been hypothesized as a major influence on the evolution of the Martian atmosphere due to the lack of a Martian global dipole magnetic field. We use 10 years (2007–2017) of Mars Express data to quantify the ion escape rate over the fully sampled parameter space of upstream solar wind dynamic pressure, pdyn, and solar photoionizing flux, FXUV. The modeled dependence on the upstream parameters indicates a near‐linear dependence on FXUV and weak negative correlation with pdyn. Integrating total heavy ion escape back through time, considering the evolution of the upstream parameters and the modeled trends, can only account for an estimated 4.8 ± 1.1 mbar of atmosphere lost as ions since the middle to late Hesperian (∼3.3 Ga ago). Accounting for the recently reported stability of ion escape through the energetic oxygen ion plume provides an upper estimate of ∼6 mbar lost. Extending the extrapolation to the late Noachian (3.9 Ga ago) accounts for 6.3 ± 1.9 mbar, and analogously up to ∼9 mbar, lost through ion escape since that time. Thus, the ion escape trends observed by Mars Express indicate that atmospheric ion escape contributed only a minor role in the evolution of the Martian atmosphere. We also report solar wind control of the cold ion outflow channel, providing a tentative explanation for the low response of the ion escape rate to upstream solar wind.
A Configuration Space Model for Intermediate‐Scale Ionospheric Structure
Authors: Rino Charles , Carrano Charles , Groves Keith , Yokoyama Tatsuhiro
Published: November 2018

Stochastic ionospheric structure is characterized by spectral density functions (SDFs), which are formally the average intensity of Fourier transformations of the electron density structure. Structure elongation along magnetic field lines is typically accommodated by constraining contours of constant spatial correlation to field‐aligned ellipsoidal surfaces. Structure realizations are generated by imposing the square root of the SDF onto uncorrelated random Fourier modes. The approach has been used successfully for interpreting both in situ and remote propagation diagnostics. However, the only connection to the field‐aligned structures generated by the underlying instability mechanism is the correlation scale. This paper introduces a configuration space model that constructs realizations as summations of field‐aligned elemental striations with a prescribed scale and peak electron density. We show that by choosing the contributing scales according to a bifurcation rule and imposing a power law intensity scaling, the corresponding SDF closely approximates an inverse power law. Thus, configuration space realizations can be structured to reproduce prescribed or measured SDFs from one‐dimensional scans. Stochastic variation comes from an imposed random distribution of striation locations, which are defined by their intercept in a reference slice plane. To conform more directly to physics‐based simulations, the striations can be interpreted as voids in the background electron density. The model is designed to support propagation simulations with arbitrary propagation angles relative to the local magnetic field direction. Relations between in situ structure and diagnostic measurements as well as phase screen equivalence can be explored.
Development and evaluation of a novel series of Nitroxoline-derived BET inhibitors with antitumor activity in renal cell carcinoma
Authors: Chen Wei , Zhang Hao , Chen Zhifeng , Jiang Hao , Liao Liping , Fan Shijie , Xing Jing , Xie Yiqian , Chen Shijie , Ding Hong , Chen Kaixian , Jiang Hualiang , Luo Cheng , Zheng Mingyue , Yao Zhiyi , Huang Yiran , Zhang Yuanyuan
Published: November 2018

Small molecular inhibitors targeting BRD4 family proteins are emerging as promising therapies in many types of human malignancies. However, whether BRD4, as well as other BET family members, may serve as therapeutic targets in renal cell carcinoma (RCC) remains unknown. In this study, we found that both BRD2 and BRD4 were over-expressed in RCC tissues, knock-down both of which achieved potent anti-proliferative effects in RCC cells. A novel category of BET inhibitors, originated from an approved drug Nitroxoline, were synthesized and evaluated with biochemical and cellular assays, as well as the method of crystallography. The complex crystal structures of several compounds in this category with the first bromodomain of BRD4 (BRD4-BD1) were solved, revealing the binding mechanism and facilitating further structural optimizations. Among them, compound BDF-1253 showed an approximately four-fold improvement in BRD4 inhibition compared with the prototype Nitroxoline and had good selectivity for BET proteins against other bromodomain proteins or epi-enzymes in biochemical assays. Compound BDF-1253 efficiently suppressed the expression of BET downstream genes, impaired RCC cells viability via inducing cell cycle arrest and apoptosis, and decreased tumor growth in RCC xenografts. In summary, these results suggest that inhibition of BET family members has great therapeutic potentials in the treatment of RCC, and the novel series of BET inhibitors reported here are promising to become RCC drug candidates.
CDC20B is required for deuterosome-mediated centriole production in multiciliated cells
Authors: Revinski Diego R. , Zaragosi Laure-Emmanuelle , Boutin Camille , Ruiz-Garcia Sandra , Deprez Marie , Thomé Virginie , Rosnet Olivier , Gay Anne-Sophie , Mercey Olivier , Paquet Agnès , Pons Nicolas , Ponzio Gilles , Marcet Brice , Kodjabachian Laurent , Barbry Pascal
Published: November 2018

Multiciliated cells (MCCs) harbor dozens to hundreds of motile cilia, which generate hydrodynamic forces important in animal physiology. In vertebrates, MCC differentiation involves massive centriole production by poorly characterized structures called deuterosomes. Here, single-cell RNA sequencing reveals that human deuterosome stage MCCs are characterized by the expression of many cell cycle-related genes. We further investigated the uncharacterized vertebrate-specific cell division cycle 20B (CDC20B) gene, which hosts microRNA-449abc. We show that CDC20B protein associates to deuterosomes and is required for centriole release and subsequent cilia production in mouse and Xenopus MCCs. CDC20B interacts with PLK1, a kinase known to coordinate centriole disengagement with the protease Separase in mitotic cells. Strikingly, over-expression of Separase rescues centriole disengagement and cilia production in CDC20B-deficient MCCs. This work reveals the shaping of deuterosome-mediated centriole production in vertebrate MCCs, by adaptation of canonical and recently evolved cell cycle-related molecules.
Establishment and characterization of new tumor xenografts and cancer cell lines from EBV-positive nasopharyngeal carcinoma
Authors: Lin Weitao , Yip Yim Ling , Jia Lin , Deng Wen , Zheng Hong , Dai Wei , Ko Josephine Mun Yee , Lo Kwok Wai , Chung Grace Tin Yun , Yip Kevin Y. , Lee Sau-Dan , Kwan Johnny Sheung-Him , Zhang Jun , Liu Tengfei , Chan Jimmy Yu-Wai , Kwong Dora Lai-Wan , Lee Victor Ho-Fun , Nicholls John Malcolm , Busson Pierre , Liu Xuefeng , Chiang Alan Kwok Shing , Hui Kwai Fung , Kwok Hin , Cheung Siu Tim , Cheung Yuk Chun , Chan Chi Keung , Li Bin , Cheung Annie Lai-Man , Hau Pok Man , Zhou Yuan , Tsang Chi Man , Middeldorp Jaap , Chen Honglin , Lung Maria Li , Tsao Sai Wah
Published: November 2018

The lack of representative nasopharyngeal carcinoma (NPC) models has seriously hampered research on EBV carcinogenesis and preclinical studies in NPC. Here we report the successful growth of five NPC patient-derived xenografts (PDXs) from fifty-eight attempts of transplantation of NPC specimens into NOD/SCID mice. The take rates for primary and recurrent NPC are 4.9% and 17.6%, respectively. Successful establishment of a new EBV-positive NPC cell line, NPC43, is achieved directly from patient NPC tissues by including Rho-associated coiled-coil containing kinases inhibitor (Y-27632) in culture medium. Spontaneous lytic reactivation of EBV can be observed in NPC43 upon withdrawal of Y-27632. Whole-exome sequencing (WES) reveals a close similarity in mutational profiles of these NPC PDXs with their corresponding patient NPC. Whole-genome sequencing (WGS) further delineates the genomic landscape and sequences of EBV genomes in these newly established NPC models, which supports their potential use in future studies of NPC.
The deubiquitinase MYSM1 dampens NOD2-mediated inflammation and tissue damage by inactivating the RIP2 complex
Authors: Panda Swarupa , Gekara Nelson O.
Published: November 2018

NOD2 is essential for antimicrobial innate immunity and tissue homeostasis, but require tight regulation to avert pathology. A focal point of NOD2 signaling is RIP2, which upon polyubiquitination nucleates the NOD2:RIP2 complex, enabling signaling events leading to inflammation, yet the precise nature and the regulation of the polyubiquitins coordinating this process remain unclear. Here we show that NOD2 signaling involves conjugation of RIP2 with lysine 63 (K63), K48 and M1 polyubiquitin chains, as well as with non-canonical K27 chains. In addition, we identify MYSM1 as a proximal deubiquitinase that attenuates NOD2:RIP2 complex assembly by selectively removing the K63, K27 and M1 chains, but sparing the K48 chains. Consequently, MYSM1 deficient mice have unrestrained NOD2-mediated peritonitis, systemic inflammation and liver injury. This study provides a complete overview of the polyubiquitins in NOD2:RIP2 signaling and reveal MYSM1 as a central negative regulator restricting these polyubiquitins to prevent excessive inflammation.
Cohort-wide deep whole genome sequencing and the allelic architecture of complex traits
Authors: Gilly Arthur , Suveges Daniel , Kuchenbaecker Karoline , Pollard Martin , Southam Lorraine , Hatzikotoulas Konstantinos , Farmaki Aliki-Eleni , Bjornland Thea , Waples Ryan , Appel Emil V. R. , Casalone Elisabetta , Melloni Giorgio , Kilian Britt , Rayner Nigel W. , Ntalla Ioanna , Kundu Kousik , Walter Klaudia , Danesh John , Butterworth Adam , Barroso Inês , Tsafantakis Emmanouil , Dedoussis George , Moltke Ida , Zeggini Eleftheria
Published: November 2018

The role of rare variants in complex traits remains uncharted. Here, we conduct deep whole genome sequencing of 1457 individuals from an isolated population, and test for rare variant burdens across six cardiometabolic traits. We identify a role for rare regulatory variation, which has hitherto been missed. We find evidence of rare variant burdens that are independent of established common variant signals (ADIPOQ and adiponectin, P = 4.2 × 10−8; APOC3 and triglyceride levels, P = 1.5 × 10−26), and identify replicating evidence for a burden associated with triglyceride levels in FAM189B (P = 2.2 × 10−8), indicating a role for this gene in lipid metabolism.
Integrating chemical and mechanical signals through dynamic coupling between cellular protrusions and pulsed ERK activation
Authors: Yang Jr-Ming , Bhattacharya Sayak , West-Foyle Hoku , Hung Chien-Fu , Wu T.-C. , Iglesias Pablo A. , Huang Chuan-Hsiang
Published: November 2018

The Ras-ERK signaling pathway regulates diverse cellular processes in response to environmental stimuli and contains important therapeutic targets for cancer. Recent single cell studies revealed stochastic pulses of ERK activation, the frequency of which determines functional outcomes such as cell proliferation. Here we show that ERK pulses are initiated by localized protrusive activities. Chemically and optogenetically induced protrusions trigger ERK activation through various entry points into the feedback loop involving Ras, PI3K, the cytoskeleton, and cellular adhesion. The excitability of the protrusive signaling network drives stochastic ERK activation in unstimulated cells and oscillations upon growth factor stimulation. Importantly, protrusions allow cells to sense combined signals from substrate stiffness and the growth factor. Thus, by uncovering the basis of ERK pulse generation we demonstrate how signals involved in cell growth and differentiation are regulated by dynamic protrusions that integrate chemical and mechanical inputs from the environment.
Author Correction: A comprehensive map coupling histone modifications with gene regulation in adult dopaminergic and serotonergic neurons
Authors: Södersten Erik , Toskas Konstantinos , Rraklli Vilma , Tiklova Katarina , Björklund Åsa K. , Ringnér Markus , Perlmann Thomas , Holmberg Johan
Published: November 2018

In the originally published version of this Article, financial support was not fully acknowledged. The PDF and HTML versions of the Article have now been corrected to include support to Thomas Perlmann provided by Knut and Alice Wallenberg Foundation (grant 2013.0075) and Swedish Research Council (VR; grant 2016-02506).
Author Correction: The structure of the ubiquitin-like modifier FAT10 reveals an alternative targeting mechanism for proteasomal degradation
Authors: Aichem Annette , Anders Samira , Catone Nicola , Rößler Philip , Stotz Sophie , Berg Andrej , Schwab Ricarda , Scheuermann Sophia , Bialas Johanna , Schütz-Stoffregen Mira C. , Schmidtke Gunter , Peter Christine , Groettrup Marcus , Wiesner Silke
Published: November 2018

The original version of the Supplementary Information associated with this Article inadvertently omitted Supplementary Table 3. The HTML version of the Article has been updated to include a corrected version of the Supplementary Information.
Author Correction: Parallels between experimental and natural evolution of legume symbionts
Authors: Clerissi Camille , Touchon Marie , Capela Delphine , Tang Mingxing , Cruveiller Stéphane , Genthon Clémence , Lopez-Roques Céline , Parker Matthew A. , Moulin Lionel , Masson-Boivin Catherine , Rocha Eduardo P. C.
Published: November 2018

Clémence Genthon and Céline Lopez-Roques, who performed sequencing, were inadvertently omitted from the author list. This has now been corrected in the PDF and HTML versions of the Article.
Modeling glass corrosion with GRAAL
Authors: Frugier Pierre , Minet Yves , Rajmohan Natarajan , Godon Nicole , Gin Stéphane
Published: November 2018

Computational codes are necessary tools for geochemical modeling of the alteration of minerals due to their ability to handle key mechanisms, such as dissolution, precipitation, diffusion, and convection at many temporal and spatial resolutions. Modeling glass corrosion specifically requires a description of the amorphous layer that forms on the surface of the glass and its effect on glass alteration kinetics. The objective of the GRAAL model (glass reactivity in allowance of the alteration layer) is both to provide a simple implementation of the passivation process in a reactive transport code and to provide data relative to the composition and the solubility of the amorphous layer. The size and properties of the protective amorphous layer drives the glass alteration rate, with regard to passivation; the greater the quantity of the protective amorphous layer, the lower the dissolution rate of the primary mineral. Here, concepts, equations, and implementation of GRAAL are reported. Simple glass alteration experiments are used to apply the model and measure parameters. The International Simple Glass used for nuclear glass long-term behavior studies is at the center of the glass compositions studied.
Growth Mechanisms and Electronic Properties of Vertically Aligned MoS2
Authors: Stern Chen , Grinvald Shmuel , Kirshner Moshe , Sinai Ofer , Oksman Mark , Alon Hadas , Meiron Oren E. , Bar-Sadan Maya , Houben Lothar , Naveh Doron
Published: November 2018

Thin films of layered semiconductors emerge as highly promising materials for energy harvesting and storage, optoelectronics and catalysis. Their natural propensity to grow as oriented crystals and films is one of their distinct properties under recent focal interest. Specifically, the reaction of transition metal films with chalcogen vapor can result in films of vertically aligned (VA) layers, while metal-oxides react with chalcogens in vapor phase to produce horizontally aligned crystals and films. The growth mechanisms of vertically oriented films are not yet fully understood, as well as their dependence on the initial metal film thickness and growth conditions. Moreover, the resulting electronic properties and the role of defects and disorder had not yet been studied, despite their critical influence on catalytic and device performance. In this work, we study the details of oriented growth of MoS2 with complementary theoretical and experimental approaches. We present a general theoretical model of diffusion-reaction growth that can be applied to a large variety of layered materials synthesized by solid-vapor reaction. Moreover, we inspect the relation of electronic properties to the structure of vertically aligned MoS2 and shed light on the density and character of defects in this material. Our measurements on Si-MoS2 p-n hetero-junction devices point to the existence of polarizable defects that impact applications of vertical transition-metal dichalcogenide materials.
Maternal High-Fat Diet Programs Offspring Liver Steatosis in a Sexually Dimorphic Manner in Association with Changes in Gut Microbial Ecology in Mice
Authors: Wankhade Umesh D. , Zhong Ying , Kang Ping , Alfaro Maria , Chintapalli Sree V. , Piccolo Brian D. , Mercer Kelly E. , Andres Aline , Thakali Keshari M. , Shankar Kartik
Published: November 2018

The contributions of maternal diet and obesity in shaping offspring microbiome remain unclear. Here we employed a mouse model of maternal diet-induced obesity via high-fat diet feeding (HFD, 45% fat calories) for 12 wk prior to conception on offspring gut microbial ecology. Male and female offspring were provided access to control or HFD from weaning until 17 wk of age. Maternal HFD-associated programming was sexually dimorphic, with male offspring from HFD dams showing hyper-responsive weight gain to postnatal HFD. Likewise, microbiome analysis of offspring cecal contents showed differences in α-diversity, β-diversity and higher Firmicutes in male compared to female mice. Weight gain in offspring was significantly associated with abundance of Lachnospiraceae and Clostridiaceae families and Adlercreutzia, Coprococcus and Lactococcus genera. Sex differences in metagenomic pathways relating to lipid metabolism, bile acid biosynthesis and immune response were also observed. HFD-fed male offspring from HFD dams also showed worse hepatic pathology, increased pro-inflammatory cytokines, altered expression of bile acid regulators (Cyp7a1, Cyp8b1 and Cyp39a1) and serum bile acid concentrations. These findings suggest that maternal HFD alters gut microbiota composition and weight gain of offspring in a sexually dimorphic manner, coincident with fatty liver and a pro-inflammatory state in male offspring.
Surface potential and thin film quality of low work function metals on epitaxial graphene
Authors: DeJarld Matthew , Campbell Paul M. , Friedman Adam L. , Currie Marc , Myers-Ward Rachael L. , Boyd Anthony K. , Rosenberg Samantha G. , Pavunny Shojan P. , Daniels Kevin M. , Gaskill D. K.
Published: November 2018

Metal films deposited on graphene are known to influence its electronic properties, but little is known about graphene’s interactions with very low work function rare earth metals. Here we report on the work functions of a wide range of metals deposited on n-type epitaxial graphene (EG) as measured by Kelvin Probe Force Microscopy (KPFM). We compare the behaviors of rare earth metals (Pr, Eu, Er, Yb, and Y) with commonly used noble metals (Cr, Cu, Rh, Ni, Au, and Pt). The rare earth films oxidize rapidly, and exhibit unique behaviors when on graphene. We find that the measured work function of the low work function group is consistently higher than predicted, unlike the noble metals, which is likely due to rapid oxidation during measurement. Some of the low work function metals interact with graphene; for example, Eu exhibits bonding anomalies along the metal-graphene perimeter. We observe no correlation between metal work function and photovoltage, implying the metal-graphene interface properties are a more determinant factor. Yb emerges as the best choice for future applications requiring a low-work function electrical contact on graphene. Yb films have the strongest photovoltage response and maintains a relatively low surface roughness, ~5 nm, despite sensitivity to oxidation.
Communicating Two States in Perovskite Revealed by Time-Resolved Photoluminescence Spectroscopy
Authors: Chen Yanwen , Wang Tianmeng , Li Zhipeng , Li Huanbin , Ye Tao , Wetzel Christian , Li Hanying , Shi Su-Fei
Published: November 2018

Organic-inorganic perovskite as a promising candidate for solar energy harvesting has attracted immense interest for its low-cost preparation and extremely high quantum efficiency. However, the fundamental understanding of the photophysics in perovskite remains elusive. In this work, we have revealed two distinct states in MAPbI3 thin films at low temperature through time-resolved photoluminescence spectroscopy (TRPL). In particular, we observed a photo-induced carrier injection from the high energy (HE) state to the low energy (LE) state which has a longer lifetime. The strong interaction between the two states, evidenced by the injection kinetics, can be sensitively controlled through the excitation power. Understanding of the interacting two-states not only sheds light on the long PL lifetime in perovskite but also helps to understand the different behavior of perovskite in response to different excitation power. Further efforts in modifying the low energy state could significantly improve the quantum efficiency and lead to novel application in optoelectronics based on perovskite.
Scaffold-Hopping from Synthetic Drugs by Holistic Molecular Representation
Authors: Grisoni Francesca , Merk Daniel , Byrne Ryan , Schneider Gisbert
Published: November 2018

The discovery of novel ligand chemotypes allows to explore uncharted regions in chemical space, thereby potentially improving synthetic accessibility, potency, and the drug-likeness of molecules. Here, we demonstrate the scaffold-hopping ability of the new Weighted Holistic Atom Localization and Entity Shape (WHALES) molecular descriptors compared to seven state-of-the-art molecular representations on 30,000 compounds and 182 biological targets. In a prospective application, we apply WHALES to the discovery of novel retinoid X receptor (RXR) modulators. WHALES descriptors identified four agonists with innovative molecular scaffolds, populating uncharted regions of the chemical space. One of the agonists, possessing a rare non-acidic chemotype, revealed high selectivity on 12 nuclear receptors and comparable efficacy as bexarotene on induction of ATP-binding cassette transporter A1, angiopoietin like protein 4 and apolipoprotein E. The outcome of this research supports WHALES as an innovative tool to explore novel regions of the chemical space and to detect novel bioactive chemotypes by straightforward similarity searching.
Microbiome shifts with onset and progression of Sea Star Wasting Disease revealed through time course sampling
Authors: Lloyd Melanie M. , Pespeni Melissa H.
Published: November 2018

The recent outbreak of Sea Star Wasting Disease (SSWD) is one of the largest marine epizootics in history, but the host-associated microbial community changes specific to disease progression have not been characterized. Here, we sampled the microbiomes of ochre sea stars, Pisaster ochraceus, through time as animals stayed healthy or became sick and died with SSWD. We found community-wide differences in the microbiomes of sick and healthy sea stars, changes in microbial community composition through disease progression, and a decrease in species richness of the microbiome in late stages of SSWD. Known beneficial taxa (Pseudoalteromonas spp.) decreased in abundance at symptom onset and through disease progression, while known pathogenic (Tenacibaculum spp.) and putatively opportunistic bacteria (Polaribacter spp. and Phaeobacter spp.) increased in abundance in early and late disease stages. Functional profiling revealed microbes more abundant in healthy animals performed functions that inhibit growth of other microbes, including pathogen detection, biosynthesis of secondary metabolites, and degradation of xenobiotics. Changes in microbial composition with disease onset and progression suggest that a microbial imbalance of the host could lead to SSWD or be a consequence of infection by another pathogen. This work highlights the importance of the microbiome in SSWD and also suggests that a healthy microbiome may help confer resistance to SSWD.
Dnmt1 has an essential function despite the absence of CpG DNA methylation in the red flour beetle Tribolium castaneum
Authors: Schulz Nora K. E. , Wagner C. Isabel , Ebeling Julia , Raddatz Günter , Diddens-de Buhr Maike F. , Lyko Frank , Kurtz Joachim
Published: November 2018

Epigenetic mechanisms, such as CpG DNA methylation enable phenotypic plasticity and rapid adaptation to changing environments. CpG DNA methylation is established by DNA methyltransferases (DNMTs), which are well conserved across vertebrates and invertebrates. There are insects with functional DNA methylation despite lacking a complete set of Dnmts. But at least one of the enzymes, DNMT1, appears to be required to maintain an active DNA methylation system. The red flour beetle, Tribolium castaneum, lacks Dnmt3 but possesses Dnmt1 and it has been controversial whether it has a functional DNA methylation system. Using whole genome bisulfite sequencing, we did not find any defined patterns of CpG DNA methylation in embryos. Nevertheless, we found Dnmt1 expressed throughout the entire life cycle of the beetle, with mRNA transcripts significantly more abundant in eggs and ovaries. A maternal knockdown of Dnmt1 caused a developmental arrest in offspring embryos. We show that Dnmt1 plays an essential role in T. castaneum embryos and that its downregulation leads to an early developmental arrest. This function appears to be unrelated to DNA methylation, since we did not find any evidence for this modification. This strongly suggests an alternative role of this protein.
Hyponatremia in children with respiratory infections: a cross-sectional analysis of a cohort of 3938 patients
Authors: Park Sung Won , Shin Son Moon , Jeong Moonsun , Cho Dong-Hee , Lee Keum Hwa , Eisenhut Michael , Kronbichler Andreas , Moritz Michael , Il Shin Jae
Published: November 2018

Hyponatremia can be a life-threatening illness among hospitalized children. The aims of this study were to evaluate the incidence and risk factors of hyponatremia in 3938 children who were admitted to the Cheil General Hospital and Women’s Health Care Center with respiratory infections. Clinical data were collected, and multiplex RT-PCR analyses were done for various microorganisms. Hyponatremia was observed in 531 (13.5%) patients. The incidence of hyponatremia differed according to the respiratory tract infection (P < 0.0001) and microorganism (P = 0.001). In children with hyponatremia, the age at admission was significantly older (P < 0.0001), male gender was more frequent (P = 0.019), CRP was higher (P < 0.0001), and coinfection with multiple organisms was more common (P = 0.001) than in children without hyponatremia. In multivariate analyses, an older age at admission (P = 0.006), male gender (P = 0.004), and increased CRP (P < 0.0001) were independent risk factors. Sodium levels correlated negatively with WBC (P = 0.037), CRP (P < 0.0001), and number of hospital days (P = 0.020). The AUC values of age (0.586, P < 0.0001), CRP (0.599, P < 0.0001), and blood urea nitrogen (0.559, P < 0.0001) were all significant predictors of hyponatremia. This study is the first to show that the incidence of hyponatremia differs according to infecting microorganism and radiological findings.
Disease severity enhancement by an esterase from non-phytopathogenic yeast Pseudozyma antarctica and its potential as adjuvant for biocontrol agents
Authors: Ueda Hirokazu , Kurose Daisuke , Kugimiya Soichi , Mitsuhara Ichiro , Yoshida Shigenobu , Tabata Jun , Suzuki Ken , Kitamoto Hiroko
Published: November 2018

The phylloplane yeast Pseudozyma antarctica secretes an esterase, named PaE, and xylanase when cultivated with xylose. We previously observed that the lipophilic layer of Micro-Tom tomato leaves became thinner after the culture filtrate treatment. The leaves developed reduced water-holding ability and became wilted. In this study, the purified enzymes were spotted on Micro-Tom leaves. PaE, but not xylanase, thinned the lipophilic layer of leaves and decreased leaf resistance to the phytopathogenic fungus Botrytis cinerea. Disease severity increased significantly in detached leaves and potted plants treated with the culture filtrate and B. cinerea spores compared with those treated with inactivated enzyme and B. cinerea alone. Spore germination ratios, numbers of penetrating fungal hyphae in the leaves, and fungal DNA contents also increased significantly on the detached leaves. Japanese knotweed (Fallopia japonica), a serious invasive alien weed in Europe and North America, also became susceptible to infection by the rust pathogen Puccinia polygoni-amphibii var. tovariae following the culture filtrate treatment. The culture filtrate treatment increased disease development in plants induced by both phytopathogenic fungi. Our results suggest that P. antarctica culture filtrate could be used as an adjuvant for sustainable biological weed control using phytopathogenic fungi.
Magnetoresistive biosensors with on-chip pulsed excitation and magnetic correlated double sampling
Authors: Kim Kyunglok , Hall Drew A. , Yao Chengyang , Lee Jung-Rok , Ooi Chin C. , Bechstein Daniel J. B. , Guo Yue , Wang Shan X.
Published: November 2018

Giant magnetoresistive (GMR) sensors have been shown to be among the most sensitive biosensors reported. While high-density and scalable sensor arrays are desirable for achieving multiplex detection, scalability remains challenging because of long data acquisition time using conventional readout methods. In this paper, we present a scalable magnetoresistive biosensor array with an on-chip magnetic field generator and a high-speed data acquisition method. The on-chip field generators enable magnetic correlated double sampling (MCDS) and global chopper stabilization to suppress 1/f noise and offset. A measurement with the proposed system takes only 20 ms, approximately 50× faster than conventional frequency domain analysis. A corresponding time domain temperature correction technique is also presented and shown to be able to remove temperature dependence from the measured signal without extra measurements or reference sensors. Measurements demonstrate detection of magnetic nanoparticles (MNPs) at a signal level as low as 6.92 ppm. The small form factor enables the proposed platform to be portable as well as having high sensitivity and rapid readout, desirable features for next generation diagnostic systems, especially in point-of-care (POC) settings.
Ultrafast laser printing of self-organized bimetallic nanotextures for multi-wavelength biosensing
Authors: Pavlov D. , Syubaev S. , Cherepakhin A. , Sergeev A. , Vitrik O. , Zakharenko A. , Danilov P. , Saraeva I. , Kudryashov S. , Porfirev A. , Kuchmizhak A.
Published: November 2018

Surface-enhanced spectroscopy (SES) techniques, including surface-enhanced photoluminescence (SEPL), Raman scattering (SERS) and infrared absorption (SEIRA), represent powerful biosensing modalities, allowing non-invasive label-free identification of various molecules and quantum emitters in the vicinity of nanotextured surfaces. Enhancement of multi-wavelength (vis-IR) excitation of analyte molecules of interest atop a single textured substrate could pave the way toward ultimate chemosensing performance and further widespread implementation of the SES-based approaches in various crucial areas, such as point-ofcare diagnostics. In this paper, an easy-to-implement ultrafast direct laser printing via partial spallation of thermally-thick silver films and subsequent large-scale magnetron deposition of nanometer-thick Au layers of variable thickness was implemented to produce bimetallic textured surfaces with the cascaded nanotopography. The produced bimetallic textures demonstrate the strong broadband plasmonic response over the entire visible spectral range. Such plasmonic performance was confirmed by convenient spectroscopy-free Red-Green-Blue (RGB) color analysis of the dark-field (DF) scattering images supported by numerical calculations of the electromagnetic (EM) “near-fields”, as well as comprehensive DF spectroscopic characterization. Bimetallic laser-printed nanotextures, which can be easily printed at ultrafast (square millimeters per second) rate, using galvanometric scanning, exhibited strong enhancement of the SEPL (up to 75-fold) and SERS (up to 106 times) yields for the organic dye molecules excited at various wavelengths. Additionally, comprehensive optical and sensing characterization of the laser-printed bimetallic surface structures allows substantiating the convenient spectroscopy-free RGB color analysis as a valuable tool for predictive assessment of the plasmonic properties of the various irregularly and quasi-periodically nanotextured surfaces.
Loss of Sirt2 increases and prolongs a caerulein-induced pancreatitis permissive phenotype and induces spontaneous oncogenic Kras mutations in mice
Authors: Quan Songhua , Principe Daniel R. , Dean Angela E. , Park Seong-Hoon , Grippo Paul J. , Gius David , Horikoshi Nobuo
Published: November 2018

Mice lacking Sirt2 spontaneously develop tumors in multiple organs, as well as when expressed in combination with oncogenic KrasG12D, leading to pancreatic tumors. Here, we report that after caerulein-induced pancreatitis, Sirt2-deficient mice exhibited an increased inflammatory phenotype and delayed pancreatic tissue recovery. Seven days post injury, the pancreas of Sirt2−/− mice display active inflammation, whereas wild-type mice had mostly recovered. In addition, the pancreas from the Sirt2−/− mice exhibited extensive tissue fibrosis, which was still present at six weeks after exposure. The mice lacking Sirt2 also demonstrated an enhanced whole body pro-inflammatory phenotype that was most obvious with increasing age. Importantly, an accumulation of a cell population with spontaneous cancerous KrasG12D mutations was observed in the Sirt2−/− mice that is enhanced in the recovering pancreas after exposure to caerulein. Finally, transcriptome analysis of the pancreas of the Sirt2−/− mice exhibited a pro-inflammatory genomic signature. These results suggest that loss of Sirt2, as well as increased age, enhanced the immune response to pancreatic injury and induced an inflammatory phenotype permissive for the accumulation of cells carrying oncogenic Kras mutations.
Piezoelectric Accelerator
Authors: Ivashchuk O. O. , Shchagin A. V. , Kubankin A. S. , Nikulin I. S. , Oleinik A. N. , Miroshnik V. S. , Volkov V. I.
Published: November 2018

Here we propose the conception of small-size piezoelectric accelerator of charged particles that operates due to the piezoelectric effect at varying mechanical force applied to piezoelectrics in vacuum. The accelerating voltage and the energy of accelerated particles are estimated. In the proof-of-principle experiment we demonstrate the effect of the emission of X-ray radiation at the mechanical compression of piezoelectric ceramics in vacuum. The compression leads to the appearance of charges and potentials on the surfaces of the piezoelectrics and also to the arising of the electric field in vacuum. Electrons are accelerated in the electric field, strike the matter and produce the X-ray radiation. In the experiment, we have observed emission of the characteristic and bremsstrahlung X-ray radiation of energy up to 60 keV due to the compression of piezoelectric ceramics in vacuum. This means that electrons are accelerated in the piezoelectric accelerator up to the energy at least of 60 keV. The agreement of calculated and experimental data confirms the conception. Advantages of the piezoelectric accelerator and possibilities of its development and applications are discussed.
Cellular signaling and gene expression profiles evoked by a bivalent macrocyclic peptide that serves as an artificial MET receptor agonist
Authors: Miao Wenyu , Sakai Katsuya , Ozawa Naoya , Nishiuchi Takumi , Suzuki Yoshinori , Ito Kenichiro , Morioka Tomomi , Umitsu Masataka , Takagi Junichi , Suga Hiroaki , Matsumoto Kunio
Published: November 2018

Non-native ligands for growth factor receptors that are generated by chemical synthesis are applicable to therapeutics. However, non-native ligands often regulate cellular signaling and biological responses in a different manner than native ligands. Generation of surrogate ligands comparable to native ligands is a challenging need. Here we investigated changes in signal transduction and gene expression evoked by a bivalent macrocyclic peptide (aMD5-PEG11) capable of high-affinity binding to the MET/hepatocyte growth factor (HGF) receptor. Binding of aMD5-PEG11 to the MET extracellular region was abolished by deletion of the IPT3−IPT4 domain, indicating the involvement of IPT3−IPT4 in the binding of aMD5-PEG11 to the MET receptor. aMD5-PEG11 induced dimerization and activation of the MET receptor and promoted cell migration that was comparable to induction of these activities by HGF. Signal activation profiles indicated that aMD5-PEG11 induced phosphorylation of intracellular signaling molecules, with a similar intensity and time dependency as HGF. In 3-D culture, aMD5-PEG11 as well as HGF induced epithelial tubulogenesis and up-regulated the same sets of functionally classified genes involved in multicellular organism development. Thus, a non-native surrogate ligand that consisted of a bivalent macrocyclic peptide can serve as an artificial MET receptor agonist that functionally substitutes for the native ligand, HGF.
Brain structural connectivity and neuroticism in healthy adults
Authors: Ueda Issei , Kakeda Shingo , Watanabe Keita , Sugimoto Koichiro , Igata Natsuki , Moriya Junji , Takemoto Kazuhiro , Katsuki Asuka , Yoshimura Reiji , Abe Osamu , Korogi Yukunori
Published: November 2018

Understanding the neural correlates of the neurotic brain is important because neuroticism is a risk factor for the development of psychopathology. We examined the correlation between brain structural networks and neuroticism based on NEO Five-Factor Inventory (NEO-FFI) scores. Fifty-one healthy participants (female, n = 18; male, n = 33; mean age, 38.5 ± 11.7 years) underwent the NEO-FFI test and magnetic resonance imaging (MRI), including diffusion tensor imaging and 3D T1WI. Using MRI data, for each participant, we constructed whole-brain interregional connectivity matrices by deterministic tractography and calculated the graph theoretical network measures, including the characteristic path length, global clustering coefficient, small-worldness, and betweenness centrality (BET) in 83 brain regions from the Desikan-Killiany atlas with subcortical segmentation using FreeSurfer. In relation to the BET, neuroticism score had a negative correlation in the left isthmus cingulate cortex, left superior parietal, left superior temporal, right caudal middle frontal, and right entorhinal cortices, and a positive correlation in the bilateral frontal pole, left caudal anterior cingulate cortex, and left fusiform gyrus. No other measurements showed significant correlations. Our results imply that the brain regions related to neuroticism exist in various regions, and that the neuroticism trait is likely formed as a result of interactions among these regions. This work was supported by a Grant-in-Aid for Scientific Research on Innovative Areas (Comprehensive Brain Science Network) from the Ministry of Education, Science, Sports and Culture of Japan.