bluuebunny/crossref_metadata_2025 huggingface dataset:
The Relationship between Long-Duration Gamma-Ray Flares and Solar Cosmic Rays
Authors: Hudson Hugh S.
Published: July 2018

A characteristic pattern of solar hard X-ray emission, first identified in SOL1969-03-30 by Frost & Dennis (1971), turns out to have a close association with the prolonged high-energy gamma-ray emission originally observed by Forrestet al.(1985). This identification has become clear via the observations of long-duration γ-ray flares by theFermi/LAT experiment, for example in the event SOL2014-09-01. The distinctive features of these events include flat hard X-ray spectra extending well above 100 keV, a characteristic pattern of time development, low-frequency gyrosynchrotron peaks, CME association, and gamma-rays identifiable with pion decay originating in GeV ions. The identification of these events with otherwise known solar structures nevertheless remains elusive, in spite of the wealth of EUV imagery available from SDO/AIA. The quandary is that these events have a clear association with SEPs in the high corona, and yet the gamma-ray production implicates the photosphere itself, despite the strong mirror force that should focus the particlesawayfrom the Sun We discuss the morphology of these phenomena and propose a solution to this problem.
PFSS-Based Solar Wind Forecast and the Radius of the Source-Surface
Authors: Nikolić Ljubomir
Published: July 2018

The potential-field source-surface (PFSS) model of the solar corona is a widely used tool in the space weather research and operations. In particular, the PFSS model is used in solar wind forecast models which empirically associate solar wind properties with the numerically derived coronal magnetic field. In the PFSS model, the spherical surface where magnetic field lines are forced to open is typically placed at 2.5 solar radii. However, the results presented here suggest that setting this surface (the source-surface) to lower heights can provide a better agreement between observed and modelled coronal holes during the current solar cycle. Furthermore, the lower heights of the source-surface provide a better match between observed and forecasted solar wind speed.
Structure of the Power Spectral Density of Galactic Cosmic Ray Variation during 1953-2016
Authors: Väisänen Pauli , Usoskin Ilya , Mursula Kalevi
Published: July 2018

Fluxes of galactic cosmic rays (GCR) observed at 1 AU are modulated inside the heliosphere at different time scales. Here we study the properties of the power spectral density (PSD) of galactic cosmic ray variability using hourly data from 31 neutron monitors (NM) from 1953 to 2016. We pay particular attention to the reliability of the used datasets and methods. We present the overall PSD and discuss different parts of the spectrum and the related periodicities. We find significant spectral peaks at the periods of 11 years, 1.75 years, 155 days, 27 days and 24 hours and the harmonics of the latter two peaks. We calculate a power law slope of −1.79 ± 0.13 for the period range between 50 and 130 hours and a slope of −1.34 ± 0.17 for the period range between 40 days and 3.4 years (1000 − 30000 h).
Geomagnetopause Position and Shape Dependence on Solar Wind Plasma and IMF Parameters: Analytic Model Comparison with Observations and 3-D MHD Runs
Authors: Verigin M. I. , Kotova G. A. , Bezrukikh V. V.
Published: July 2018

It is generally accepted to use the solar wind ram pressure ρV2 and the IMF Bz component for empirical description of the geo-magnetopause position and shape. A specific feature of the present paper is not to use the solar wind ρV2 but the thermal Pth and magnetic field Pmag pressures adjacent to the magnetopause for proper modelling. These pressures are deduced from the results of 3-D MHD runs and analytic solutions for post bow shock MHD flow in Lagrangian variables. The magnetopause shape variation due to Bz component changes the so called ‘doubling factor’ fd, which can be analytically deduced from a Tsyganenko magnetospheric field ellipsoidal model. Including all the above effects in our analytical model leads to a good description of ‘rapid’ magnetopause approach to the Earth for southward IMF and to its ‘stagnant’ behaviour with the increase of northward IMF component.
Reinforcing a Double Dynamo Model with Solar-Terrestrial Activity in the Past Three Millennia
Authors: Zharkova V. V. , Shepherd S. J. , Popova E. , Zharkov S. I.
Published: July 2018

By applying Principal Components Analysis (PCA) to solar magnetic synoptic maps in cycle 21-23 obtained with Wilcox Solar Observatory we derived analytical expressions for two principal components and their summary curve of solar magnetic field oscillations defined by dipole magnetic sources. In this paper we extrapolate backwards three millennia the summary curve describing solar activity and compare it with the relevant historic data. The extrapolated summary curve shows a remarkable resemblance to the sunspot and terrestrial activity reported in the past millennia: the Maunder Minimum (1645-1715), Wolf minimum (1200), Oort minimum (1010-1050), Homer minimum (800-900 BC), the medieval warm period (900-1200), the Roman warm period (400-10BC). We note that Sporer minimum (1460-1550) derived from the increased abundance of isotope Δ14C is likely produced by a strong increase of galactic cosmic rays caused by a supernova Vela Junior occurred in the Southern hemisphere.
Excitation and Evolution of Transverse Loop Oscillations by Coronal Rain
Authors: Verwichte Erwin , Kohutova Petra , Antolin Patrick , Rowlands George , Neukirch Thomas
Published: July 2018

We present evidence of the excitation of vertically polarised transverse loop oscillations triggered by a catastrophic cooling of a coronal loop with two thirds of the loop mass comprising of cool rain mass. The nature and excitation of oscillations associated with coronal rain is not well understood. We consider observations of coronal rain using data from IRIS, SOT/Hinode and AIA/SDO in a bid to elucidate the excitation mechanism and evolution of wave characteristics. We apply an analytical model of wave-rain interaction, that predicts the inertial excitation amplitude of transverse loop oscillations as a function of the rain mass, to deduce the relative rain mass. It is consistent with the evolution of the oscillation period showing the loop losing a third of its mass due to falling coronal rain in a 10-15 minute time period.
A New Technique to Provide Realistic Input to CME Forecasting Models
Authors: Gopalswamy Nat , Akiyama Sachiko , Yashiro Seiji , Xie Hong
Published: July 2018

We report on a technique to construct a flux rope (FR) from eruption data at the Sun. The technique involves line-of-sight magnetic fields, post-eruption arcades in the corona, and white-light coronal mass ejections (CMEs) so that the FR geometric and magnetic properties can be fully defined in addition to the kinematic properties. We refer to this FR as FRED (Flux Rope from Eruption Data). We illustrate the FRED construction using the 2012 July 12 eruption and compare the coronal and interplanetary properties of the FR. The results indicate that the FRED input should help make realistic predictions of the components of the FR magnetic field in the heliosphere.
High Speed Solar Wind Forecast Model from the Solar Surface to 1AU Using Global 3D MHD Simulation
Authors: Den Mitsue , Tanaka Takashi , Kubo Yuki , Watari Shinichi
Published: July 2018

Emanating from coronals holes (CHs), high speed streams (HSSs) cause recurrent geomagnetic disturbances in the Earth’s magnetosphere. For this reason being able to predict the occurrence and timing of the high speed solar wind is one of the more important issues in space weather forecasting. Currently, it is still difficult to estimate the effect of a CH in case that it extends from high latitudes to lower ones. To monitor the global solar wind condition we have therefore developed a three-dimensional MHD simulation code, the REProduce Plasma Universe (REPPU) code, that is driven by the solar magnetic field from the solar surface to 1AU. The connectivity of magnetic field lines from CHs to Earth’s orbit via HSSs has been investigated. Simulation results are presented and the usefulness of our model is discussed.
Data Handling and Assimilation for Solar Event Prediction
Authors: Martens Petrus C. , Angryk Rafal A.
Published: July 2018

The prediction of solar flares, eruptions, and high energy particle storms is of great societal importance. The data mining approach to forecasting has been shown to be very promising. Benchmark datasets are a key element in the further development of data-driven forecasting. With one or more benchmark data sets established, judicious use of both the data themselves and the selection of prediction algorithms is key to developing a high quality and robust method for the prediction of geo-effective solar activity. We review here briefly the process of generating benchmark datasets and developing prediction algorithms.
Four-Spacecraft Magnetic Curvature Analysis on Kelvin-Helmholtz Waves in MHD Simulations
Authors: Kieokaew R. , Foullon C. , Lavraud B.
Published: July 2018

Four-spacecraft missions are probing the Earth’s magnetospheric environment with high potential for revealing spatial and temporal scales of a variety of in-situ phenomena. Magnetic curvature is intrinsic to curved magnetic fields where the magnetic energy is stored in the form of magnetic tension. In-situ magnetic curvature has been resolved by the four-spacecraft technique called “magnetic curvature analysis” (MCA). We test the MCA on 2.5D MHD simulations of curved magnetic structures induced by Kelvin-Helmholtz (KH) waves, with increasing (regular) tetrahedron sizes of virtual spacecraft. We have found variations of the curvature vectors both in radii and orientations depending on the sizes of the tetrahedron. This is helpful to better understand the MCA measures when the technique is applied to in-situ data without knowing the scale sizes of plasma structures under consideration. This study lends support for cross-scale observations to better understand the nature of curvature and its role in plasma phenomena.
Numerical Short-Term Solar Activity Forecasting
Authors: Wang Huaning , Yan Yihua , He Han , Huang Xin , Dai Xinghua , Zhu Xiaoshuai , Du Zhanle , Zhao Hui , Yan Yan
Published: July 2018

It is well known that the energy for solar eruptions comes from magnetic fields in solar active regions. Magnetic energy storage and dissipation are regarded as important physical processes in the solar corona. With incomplete theoretical modeling for eruptions in the solar atmosphere, activity forecasting is mainly supported with statistical models. Solar observations with high temporal and spatial resolution continuously from space well describe the evolution of activities in the solar atmosphere, and combined with three dimensional reconstruction of solar magnetic fields, makes numerical short-term (within hours to days) solar activity forecasting possible. In the current report, we propose the erupting frequency and main attack direction of solar eruptions as new forecasts and present the prospects for numerical short-term solar activity forecasting based on the magnetic topological framework in solar active regions.
Analysis of Magnetic Field Variations Produced by Equatorial Electro-Jets
Authors: López Ericson , Aldás Franklin , Yoshikawa Akimasa
Published: July 2018

The Equatorial Electrojet (EEJ) is a narrow band of electrons flowing from east to west at daytime at low latitudes. The electron current produces a magnetic field variation that can be measured at different latitudes. In this work, we have used the data analysis in order to quantify the solar and lunar contributions to those variations and study the morphology of the EEJ current.
JUSTIFYING THE WORLD AS AN AESTHETIC PHENOMENON
Authors: Halliwell Stephen
Published: July 2018

This article scrutinises one of the most challenging theses of Nietzsche'sBirth of Tragedy, that only as an aesthetic phenomenon can existence and the world be (or appear to be) ‘justified’. Through a close examination of the work's frequently masked revaluation of a series of Greek sources of thinking, not least its ‘inversion’ of both the metaphysics and the aesthetics of Plato'sRepublic, the article shows how the thesis of aesthetic ‘justification’ is caught up in a tension between Apolline and Dionysian interpretations, the first entailing a quasi-Homeric sense that the Olympians justify human existence by living a transfigured form of it themselves, the second involving a tragic insight into reality as itself the creative work of a ‘world-artist’, the latter allusively associated by Nietzsche with the philosophy of Heraclitus.
Pornography Consumption and Sexual Satisfaction in a Korean	Sample
Authors: Wright Paul J. , Miezan Ekra , Sun Chyng
Published: July 2018

Abstract. This research report assessed pornography consumption and sexual satisfaction in a heterosexual sample of Korean adults. Consistent with prior studies, the linear association between pornography consumption and satisfaction was negative and significant. However, the addition of a quadratic term to the equation increased model fit. Interaction effect analyses revealed an inverted U relationship for both men and women, such that occasional pornography consumption was associated with higher satisfaction, while consumption with any degree of regularity was associated with lower satisfaction. Further assessments showed that the negative relationship between more regular pornography consumption and lower satisfaction was slightly more marked for women, while the positive relationship between intermittent pornography consumption and higher satisfaction was slightly more marked for men. The nature of the relationship between pornography consumption and satisfaction was similar for religious and nonreligious people and for people in a relationship and not in a relationship.
The Advective‐Diffusive Morphodynamics of Mixed Bedrock‐Alluvial Rivers Subjected to Spatiotemporally Varying Sediment Supply
Authors: Zhang Li , Stark Colin , Schumer Rina , Kwang Jeffrey , Li Tiejian , Fu Xudong , Wang Guangqian , Parker Gary
Published: July 2018

Mountain rivers subject to earthquakes and intense precipitation have highly variable sediment supply rates. Here we consider the morphodynamics of 1‐D mixed bedrock‐alluvial rivers with temporally varying sediment supply rates. We use a periodic sedimentograph, characterized by short periods of high sediment feed rate and longer periods of low sediment feed rate. We study the problem with a corrected Macroroughness Saltation‐Abrasion‐Alluviation model. In this model, incision is driven by bedload colliding with bedrock, but incision can be turned off by either zero sediment transport or complete alluviation. The formulation is advective‐diffusive, the former capturing upstream‐migrating knickpoints and the latter capturing smearing of the sedimentograph downstream. The steady state balance between incision and uplift is characterized by a bedrock slope that varies downstream, exhibiting low values at the upstream end of the domain and higher values farther downstream. Sufficiently far downstream, the bedrock slope approaches that predicted for constant feed rates. The zone of low slope near the feed point corresponds to a pocket (zone of locally depressed bedrock slope) in the longitudinal profile, which is repeatedly drowned in and flushed of sediment. The steady state slope profile of a shorter reach is a truncated version of that of a longer reach. A limiting reach length including the pocket defines a sedimentograph boundary layer, where the effects of sediment feed fluctuation are felt.
Ten Steps to a Successful Career Launch
Authors: Waterman Makeda , Balbes Lisa , Harwell David
Published: July 2018

How to use your first months on the job strategically to explore your new role and make the connections that will carry you onward and upward.
Toward a Robust Elastic Geobarometry of Kyanite Inclusions in Eclogitic Diamonds
Authors: Nestola F. , Prencipe M. , Nimis P. , Sgreva N. , Perritt S. H. , Chinn I. L. , Zaffiro G.
Published: July 2018

Here we report the first results from elastic geobarometry applied to a kyanite inclusion entrapped within an eclogitic diamond (from Voorspoed mine, South Africa) using micro‐Raman and Fourier transform infrared spectroscopy, electron microprobe analysis, ab initio calculations, and finite element modeling. Application of elastic geobarometry to very elastically anisotropic kyanite inclusions is challenging, as current models do not allow for elastic anisotropy. In order to minimize the effects of anisotropy, we have explored the effects of deviatoric stress on Raman modes via ab initio density functional theory. The results allowed us to select the Raman mode (at ca. 638 cm−1) that is the least sensitive to deviatoric stress. The shift of this band in the inclusion while still trapped within the diamond relative to the inclusion in air (once liberated) was used under hydrostatic approximation to determine a residual pressure on the inclusion of 0.184 ± 0.045 GPa and an entrapment pressure of 5.2 ± 0.3 GPa (~160 km depth) for an FTIR N‐aggregation residence temperature of 1119 ± 50 °C. This is the first geothermobarometric determination for a diamond from the Voorspoed kimberlite. It overlaps with P–T estimates obtained by traditional chemical geobarometry for diamonds from other kimberlites from the Kaapvaal craton, suggesting that the hydrostatic approximation does not introduce significant errors in the geobarometric evaluation. Our protocol of Raman peak selection can be used for geobarometry of further kyanite‐bearing diamonds and may provide a guide for more robust geobarometry of other types of mineral inclusions in diamonds, both eclogitic and peridotitic.
Microbiome functioning depends on individual and interactive effects of the environment and community structure
Authors: Orland Chloé , Emilson Erik J S , Basiliko Nathan , Mykytczuk Nadia C S , Gunn John M , Tanentzap Andrew J
Published: July 2018

How ecosystem functioning changes with microbial communities remains an open question in natural ecosystems. Both present-day environmental conditions and historical events, such as past differences in dispersal, can have a greater influence over ecosystem function than the diversity or abundance of both taxa and genes. Here, we estimated how individual and interactive effects of microbial community structure defined by diversity and abundance, present-day environmental conditions, and an indicator of historical legacies influenced ecosystem functioning in lake sediments. We studied sediments because they have strong gradients in all three of these ecosystem properties and deliver important functions worldwide. By characterizing bacterial community composition and functional traits at eight sites fed by discrete and contrasting catchments, we found that taxonomic diversity and the normalized abundance of oxidase-encoding genes explained as much variation in CO2 production as present-day gradients of pH and organic matter quantity and quality. Functional gene diversity was not linked to CO2 production rates. Surprisingly, the effects of taxonomic diversity and normalized oxidase abundance in the model predicting CO2 production were attributable to site-level differences in bacterial communities unrelated to the present-day environment, suggesting that colonization history rather than habitat-based filtering indirectly influenced ecosystem functioning. Our findings add to limited evidence that biodiversity and gene abundance explain patterns of microbiome functioning in nature. Yet we highlight among the first time how these relationships depend directly on present-day environmental conditions and indirectly on historical legacies, and so need to be contextualized with these other ecosystem properties.
Macrophages confer resistance to PI3K inhibitor GDC-0941 in breast cancer through the activation of NF-κB signaling
Authors: Usman Muhammad Waqas , Gao Jing , Zheng Tiezheng , Rui Chunhua , Li Ting , Bian Xing , Cheng Hailing , Liu Pixu , Luo Fuwen
Published: July 2018

The PI3K pathway is one of the most dysregulated signaling pathways in epithelial cancers and has become an attractive therapeutic target under active preclinical and clinical development. However, recent clinical trial studies revealed that blockade of PI3K activity in advanced cancer often leads to the development of resistance and relapse of the diseases. Intense efforts have been made to elucidate resistance mechanisms and identify rational drug combinations with PI3K inhibitors in solid tumors. In the current study, we found that PI3K inhibition by GDC-0941 increased macrophage infiltration and induced the expression of macrophage-associated cytokines and chemokines in the mouse 4T1 breast tumor model. Using the in vitro co-culture system, we showed that the presence of macrophages led to the activation of NF-κB signaling in 4T1 tumor cells, rendering tumor cells resistant to PI3K inhibition by GDC-0941. Furthermore, we found that Aspirin could block the activation of NF-κB signaling induced by PI3K inhibition, and combined use of GDC-0941 and Aspirin resulted in attenuated cell growth and enhanced apoptosis of 4T1 cells in the in vitro co-culture system with the presence of macrophages. Consistently, the combination treatment also effectively reduced tumor burden, macrophage infiltration and pulmonary metastasis in in vivo 4T1 breast tumor model. Together, our results suggested macrophages in microenvironment may contribute to the resistance of breast cancer cells to PI3K inhibition and reveal a new combination paradigm to improve the efficacy of PI3K-targeted therapy.
Oxidative stress and autophagy-related changes during retinal degeneration and development
Authors: Trachsel-Moncho Laura , Benlloch-Navarro Soledad , Fernández-Carbonell Ángel , Ramírez-Lamelas Dolores Tania , Olivar Teresa , Silvestre Dolores , Poch Enric , Miranda María
Published: July 2018

Retinitis pigmentosa (RP) is an inherited retinopathy that leads to photoreceptor loss. RP has been related to oxidative stress, autophagy, and inflammation. This study aimed to identify changes in the levels of oxidative stress and autophagy markers in the retina of control and rd10 mice during different phases of retinal development. Changes in the retinal oxidation system were investigated by measuring the levels of oxidized and reduced glutathione (GSH/GSSG), retinal avidin-positive cells, and 4-hydroxynonenal (4-HNE) staining intensity. Autophagy characterization was explored by measuring the levels of microtubule-associated protein 1 light chain 3 (LC3), beclin, autophagy-related proteins 5 and 7 (Atg5 and Atg7), and lysosomal associated membrane protein-2A (LAMP-2A). At P28 retinal GSH concentrations decreased in rd10 mice compared to the controls. No differences were found in retinal GSSG concentrations between the control and rd10 mice. There was an increase in retinal GSSG concentrations and a decrease in the GSH/GSSG ratio in the control and rd10 mice at P21 and P28 compared to P13. We observed an increase in avidin-positive cells in rd10 retinas. 4-HNE was increased in rd10 retinas at P13, and it also increased in control mice with age. We did not observe any differences in the retinal levels of LC3II/I ratio, Beclin, Atg5, or Atg7 in the rd10 mice compared to the controls. There was an increase in the LAMP-2A concentrations in the control and rd10 mice with development age (P28 concentrations vs. P13). Although only slight differences were found in the oxidative stress and autophagy markers between the control and rd10 mice, there were increases in the GSSG, 4-HNE, and LAMP-2A with age. This increase in the oxidative stress and chaperone-mediated autophagy has not been described before and occurred just after the mice opened their eyes, potentially indicating a retinal response to light exposure.
Spontaneously opening GABAA receptors play a significant role in neuronal signal filtering and integration
Authors: O’Neill Nathanael , Sylantyev Sergiy
Published: July 2018

Continuous (tonic) charge transfer through ionotropic receptors of γ-aminobutyric acid (GABAARs) is an important mechanism of inhibitory signalling in the brain. The conventional view has been that tonic GABA-ergic inhibitory currents are mediated by low concentrations of ambient GABA. Recently, however, it was shown that the GABA-independent, spontaneously opening GABAARs (s-GABAARs), may contribute significantly to the tonic GABAAR current. One of the common approaches to temporal lobe epilepsy (TLE) therapy is an increase of GABA concentration in the cerebrospinal fluid to augment tonic current through GABAARs. Such an increase, however, generates multiple side effects, which impose significant limitations on the use of correspondent drugs. In contrast, activation/deactivation of s-GABAARs in a GABA-independent manner may provide a mechanism of regulation of tonic conductance without modification of extracellular GABA concentration, thus avoiding connected side effects. Although s-GABAARs have been detected in our earlier work, it is unclear whether they modulate neural signalling, or, due to their independence from the neurotransmitter, they provide just a stable background effect without much impact on neural crosstalk dynamics. Here, we focused on the causal relationship between s-GABAAR activity and signal integration in the rat’s dentate gyrus granule cells to find that s-GABAARs play an important role in neural signal transduction. s-GABAARs shape the dynamics of phasic inhibitory responses, regulate the action potential generation machinery and control the coincidence detection window pertinent to excitatory input summation. Our results demonstrate that tonic inhibition delivered by s-GABAARs contributes to the key mechanisms that ensure implementation of neural signal filtering and integration, in a GABA-independent manner. This makes s-GABAAR a new and important actor in the regulation of long-term neural plasticity and a perspective target for TLE therapy.
Stability criteria for complex microbial communities
Authors: Butler Stacey , O’Dwyer James P.
Published: July 2018

Competition and mutualism are inevitable processes in microbial ecology, and a central question is which and how many taxa will persist in the face of these interactions. Ecological theory has demonstrated that when direct, pairwise interactions among a group of species are too numerous, or too strong, then the coexistence of these species will be unstable to any slight perturbation. Here, we refine and to some extent overturn that understanding, by considering explicitly the resources that microbes consume and produce. In contrast to more complex organisms, microbial cells consume primarily abiotic resources, and mutualistic interactions are often mediated through the mechanism of crossfeeding. We show that if microbes consume, but do not produce resources, then any positive equilibrium will always be stable to small perturbations. We go on to show that in the presence of crossfeeding, stability is no longer guaranteed. However, positive equilibria remain stable whenever mutualistic interactions are either sufficiently weak, or when all pairs of taxa reciprocate each other’s assistance.
A reliable murine model of bone metastasis by injecting cancer cells through caudal arteries
Authors: Kuchimaru Takahiro , Kataoka Naoya , Nakagawa Kenji , Isozaki Tatsuhiro , Miyabara Hitomi , Minegishi Misa , Kadonosono Tetsuya , Kizaka-Kondoh Shinae
Published: July 2018

Although the current murine model of bone metastasis using intracardiac (IC) injection successfully recapitulates the process of bone metastasis, further progress in the study of bone metastasis requires a new model to circumvent some limitations of this model. Here, we present a new murine model of bone metastasis achieved by injecting cancer cells through the intra-caudal arterial (CA). This model does not require high technical proficiency, predominantly delivers cancer cells to bone marrow of hind limbs with much higher efficiency than IC injection, and greatly shortens the period of overt bone metastasis development. Moreover, CA injection barely causes acute death of mice, enabling us to inject a larger number of cancer cells to further accelerate the development of bone metastasis with a wide variety of cell lines. Our model may open a new avenue for understanding the bone metastatic processes and development of drugs preventing bone metastasis and recurrence.
Long noncoding RNA licensing of obesity-linked hepatic lipogenesis and NAFLD pathogenesis
Authors: Zhao Xu-Yun , Xiong Xuelian , Liu Tongyu , Mi Lin , Peng Xiaoling , Rui Crystal , Guo Liang , Li Siming , Li Xiaoying , Lin Jiandie D.
Published: July 2018

Hepatic lipogenesis is aberrantly induced in nonalcoholic fatty liver disease (NAFLD) via activation of the LXR-SREBP1c pathway. To date, a number of protein factors impinging on the transcriptional activity of LXR and SREBP1c have been elucidated. However, whether this regulatory axis interfaces with long noncoding RNAs (lncRNAs) remains largely unexplored. Here we show that hepatic expression of the lncRNA Blnc1 is strongly elevated in obesity and NAFLD in mice. Blnc1 is required for the induction of SREBP1c and hepatic lipogenic genes in response to LXR activation. Liver-specific inactivation of Blnc1 abrogates high-fat diet-induced hepatic steatosis and insulin resistance and protects mice from diet-induced nonalcoholic steatohepatitis. Proteomic analysis of the Blnc1 ribonucleoprotein complex identified EDF1 as a component of the LXR transcriptional complex that acts in concert with Blnc1 to activate the lipogenic gene program. These findings illustrate a lncRNA transcriptional checkpoint that licenses excess hepatic lipogenesis to exacerbate insulin resistance and NAFLD.
Controllable protein phase separation and modular recruitment to form responsive membraneless organelles
Authors: Schuster Benjamin S. , Reed Ellen H. , Parthasarathy Ranganath , Jahnke Craig N. , Caldwell Reese M. , Bermudez Jessica G. , Ramage Holly , Good Matthew C. , Hammer Daniel A.
Published: July 2018

Many intrinsically disordered proteins self-assemble into liquid droplets that function as membraneless organelles. Because of their biological importance and ability to colocalize molecules at high concentrations, these protein compartments represent a compelling target for bio-inspired materials engineering. Here we manipulated the intrinsically disordered, arginine/glycine-rich RGG domain from the P granule protein LAF-1 to generate synthetic membraneless organelles with controllable phase separation and cargo recruitment. First, we demonstrate enzymatically triggered droplet assembly and disassembly, whereby miscibility and RGG domain valency are tuned by protease activity. Second, we control droplet composition by selectively recruiting cargo molecules via protein interaction motifs. We then demonstrate protease-triggered controlled release of cargo. Droplet assembly and cargo recruitment are robust, occurring in cytoplasmic extracts and in living mammalian cells. This versatile system, which generates dynamic membraneless organelles with programmable phase behavior and composition, has important applications for compartmentalizing collections of proteins in engineered cells and protocells.
Stabilization of three-dimensional charge order in YBa2Cu3O6+x via epitaxial growth
Authors: Bluschke M. , Frano A. , Schierle E. , Putzky D. , Ghorbani F. , Ortiz R. , Suzuki H. , Christiani G. , Logvenov G. , Weschke E. , Birgeneau R. J. , da Silva Neto E. H. , Minola M. , Blanco-Canosa S. , Keimer B.
Published: July 2018

Incommensurate charge order (CO) has been identified as the leading competitor of high-temperature superconductivity in all major families of layered copper oxides, but the perplexing variety of CO states in different cuprates has confounded investigations of its impact on the transport and thermodynamic properties. The three-dimensional (3D) CO observed in YBa2Cu3O6+x in high magnetic fields is of particular interest, because quantum transport measurements have revealed detailed information about the corresponding Fermi surface. Here we use resonant X-ray scattering to demonstrate 3D-CO in underdoped YBa2Cu3O6+x films grown epitaxially on SrTiO3 in the absence of magnetic fields. The resonance profiles indicate that Cu sites in the charge-reservoir layers participate in the CO state, and thus efficiently transmit CO correlations between adjacent CuO2 bilayer units. The results offer fresh perspectives for experiments elucidating the influence of 3D-CO on the electronic properties of cuprates without the need to apply high magnetic fields.
Distribution-based measures of tumor heterogeneity are sensitive to mutation calling and lack strong clinical predictive power
Authors: Noorbakhsh Javad , Kim Hyunsoo , Namburi Sandeep , Chuang Jeffrey H.
Published: July 2018

Mutant allele frequency distributions in cancer samples have been used to estimate intratumoral heterogeneity and its implications for patient survival. However, mutation calls are sensitive to the calling algorithm. It remains unknown whether the relationship of heterogeneity and clinical outcome is robust to these variations. To resolve this question, we studied the robustness of allele frequency distributions to the mutation callers MuTect, SomaticSniper, and VarScan in 4722 cancer samples from The Cancer Genome Atlas. We observed discrepancies among the results, particularly a pronounced difference between allele frequency distributions called by VarScan and SomaticSniper. Survival analysis showed little robust predictive power for heterogeneity as measured by Mutant-Allele Tumor Heterogeneity (MATH) score, with the exception of uterine corpus endometrial carcinoma. However, we found that variations in mutant allele frequencies were mediated by variations in copy number. Our results indicate that the clinical predictions associated with MATH score are primarily caused by copy number aberrations that alter mutant allele frequencies. Finally, we present a mathematical model of linear tumor evolution demonstrating why MATH score is insufficient for distinguishing different scenarios of tumor growth. Our findings elucidate the importance of allele frequency distributions as a measure for tumor heterogeneity and their prognostic role.
Paleomagnetism of IODP Site U1380: Implications for the Forearc Deformation in the Costa Rican Erosive Convergent Margin
Authors: Li Yong-Xiang , Zhao Xixi , Xie Siyi , Jovane Luigi , Petronotis Katerina
Published: July 2018

The destructive nature of subduction erosion poses challenges to fully understanding the evolution of erosive convergent margins that are critical to understanding crustal recycling and seismogenesis. Forearc deformation holds important clues to the evolution of erosive convergent margins. Here we present detailed paleomagnetic and structural analyses of IODP Site U1380 cores from the middle slope of the forearc of the Costa Rican erosive convergent margin. The analyses reveal a strong deformation zone from ~490 to ~550 mbsf that is characterized by abundant fissility/foliations shallower than the bedding. Similar relatively strong deformation zones are recognized from the frontal prism and upper slope sites, and are broadly correlative, forming a zone of strong deformation across the forearc. This zone spans ~2.0 to 1.83 Ma and the deformation likely occurred briefly at ~1.80 Ma. The widespread, short-lived, and strong deformation is interpreted as a result of intense subhorizontal shear following the rapid forearc subsidence driven by the dramatic subduction erosion associated with the abrupt onset of the Cocos Ridge subduction. Given the typical occurrence of forearc subsidence by subduction erosion, similar styles of deformation are probably common in other erosive convergent margins as well.
Giant peak of the Inverse Faraday effect in the band gap of magnetophotonic microcavity
Authors: Kozhaev Mikhail A. , Chernov Alexander I. , Sylgacheva Daria A. , Shaposhnikov Alexander N. , Prokopov Anatoly R. , Berzhansky Vladimir N. , Zvezdin Anatoly K. , Belotelov Vladimir I.
Published: July 2018

Optical impact on the spin system in a magnetically ordered medium provides a unique possibility for local manipulation of magnetization at subpicosecond time scales. One of the mechanisms of the optical manipulation is related to the inverse Faraday effect (IFE). Usually the IFE is observed in crystals and magnetic films on a substrate. Here we demonstrate the IFE induced by fs-laser pulses in the magnetic film inside the magnetophotonic microcavity. Spectral dependence of the IFE on the laser pulse wavelength in the band gap of the magnetophotonic microcavity has a sharp peak leading to a significant enhancement of the IFE. This phenomenon is explained by strong confinement of the electromagnetic energy within the magnetic film. Calculated near field distribution of the IFE effective magnetic field indicates its subwavelength localization within 30 nm along the film thickness. These excited volumes can be shifted along the sample depth via e.g. changing frequency of the laser pulses. The obtained results open a way for ultrafast optical control of magnetization at subwavelength scales.
Rapid Nanophotonics Assay for Head and Neck Cancer Diagnosis
Authors: Vohra P. , Strobbia P. , Ngo H. T. , Lee W. T. , Vo-Dinh T.
Published: July 2018

Efficient and timely diagnosis of head and neck squamous cell carcinoma (HNSCC) is a critical challenge, particularly in low and middle income countries. These regions, which are expected to witness a drastic increase in HNSCC rates, are ill-prepared to handle the diagnostic burden due to limited resources, especially the low ratio of pathologists per population, resulting in delayed diagnosis and treatment. Here, we demonstrate the potential of an alternative diagnostic method as a low-cost, resource-efficient alternative to histopathological analysis. Our novel technology employs unique surface-enhanced Raman scattering (SERS) “nanorattles” targeting cytokeratin nucleic acid biomarkers specific for HNSCC. In this first study using SERS diagnostics for head and neck cancers, we tested the diagnostic accuracy of our assay using patient tissue samples. In a blinded trial, our technique demonstrated a sensitivity of 100% and specificity of 89%, supporting its use as a useful alternative to histopathological diagnosis. The implications of our method are vast and significant in the setting of global health. Our method can provide a rapid diagnosis, allowing for earlier treatment before the onset of distant metastases. In comparison to histopathology, which can take several months in remote limited-resources regions, our method provides a diagnosis within a few hours.
Fc-apelin fusion protein attenuates lipopolysaccharide-induced liver injury in mice
Authors: Zhou Huifen , Yang Rongze , Wang Weimin , Xu Feng , Xi Yue , Brown Robert A. , Zhang Hong , Shi Lin , Zhu Dalong , Gong Da-Wei
Published: July 2018

Apelin is a peptide hormone with anti-oxidative and anti-inflammatory activities and is proposed to be a potential therapeutic for many disease conditions, including sepsis. However, short in vivo half-life of the apelin peptide would limit its potential clinical applications. This study aims to investigate the effects of Fc-apelin, a novel long-acting apelin fusion protein, on lipopolysaccharide (LPS)-induced liver injury. Liver injury was induced by systemic injection of LPS in mice. Hepatoprotective activities of Fc-apelin against inflammation were evaluated in LPS mice and/or hepatoma Huh-7 cells with respect to serum ALT, apoptosis, oxidative stress, macrophage infiltration and gene expression. We found that LPS induced systemic inflammation and liver damage. Co-administration of Fc-apelin significantly attenuated serum ALT elevation, diminished LPS-induced apoptosis and ROS production in the liver and in Huh-7 cells, mitigated hepatic macrophage infiltration, and reduced TNFα and IL-6 gene expression. Collectively, Fc-apelin fusion protein exerts protective effects against LPS-induced liver damage and may serve as a potential therapeutic for endotoxin-induced liver injury.
Neutralization of Junín virus by single domain antibodies targeted against the nucleoprotein
Authors: Linero Florencia , Sepúlveda Claudia , Christopoulou Ioanna , Hulpiau Paco , Scolaro Luis , Saelens Xavier
Published: July 2018

The syndrome viral haemorrhagic fever (VHF) designates a broad range of diseases that are caused by different viruses including members of the family Arenaviridae. Prophylaxis for Argentine Haemorrhagic Fever (AHF), caused by the arenavirus Junín (JUNV), has been achieved by the use of a live attenuated vaccine, named Candid#1. The standard treatment of AHF is transfusion of convalescent human plasma. Our aim was to develop an alternative and safer treatment for AHF based on the use of virus-neutralizing single domain antibodies (VHHs). We describe the first reported VHHs directed against an arenavirus. These VHHs could neutralize Candid#1 by altering virion binding/fusion. Surprisingly, the neutralizing VHHs appeared to be specific for the viral nucleoprotein (N) that is not known to be involved in arenavirus entry. Candid#1 VHH-escape viruses had acquired a predicted N-glycosylation site in the surface glycoprotein GP1 that is present in highly pathogenic JUNV strains. Accordingly, the Candid#1-neutralizing VHHs could not neutralize pathogenic JUNV strains, but they could still bind to cells infected with a pathogenic strain or the escape mutant viruses. These results show that the attenuated strains of JUNV can be potently neutralized by nucleoprotein-specific VHHs.
Publisher Correction: Management of Low and Intermediate Risk Adult Rhabdomyosarcoma: A Pooled Survival Analysis of 553 Patients
Authors: Elsebaie Maha A. T. , Amgad Mohamed , Elkashash Ahmed , Elgebaly Ahmed Saber , Ashal Gehad Gamal E. l. , Shash Emad , Elsayed Zeinab
Published: July 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
LRP1 is required for novobiocin-mediated fibronectin turnover
Authors: Boel Natasha Marie-Eraine , Hunter Morgan Campbell , Edkins Adrienne Lesley
Published: July 2018

Fibronectin (FN) plays a major role in the stability and organization of the extracellular matrix (ECM). We have previously demonstrated that FN interacts directly with Hsp90, as well as showing that the Hsp90 inhibitor novobiocin results in FN turnover via a receptor mediated process. However, the receptor involved has not been previously identified. LRP1 is a ubiquitous receptor responsible for the internalisation of numerous ligands that binds both Hsp90 and FN, and therefore we investigated whether LRP1 was involved in novobiocin-mediated FN turnover. FN, LRP1 and Hsp90 could be isolated in a common complex, and inhibition of Hsp90 by novobiocin increased the colocalisation of FN and LRP1. Novobiocin induced an increase (at low concentrations) followed by a loss of FN that was primarily derived from extracellular matrix-associated FN and led to a concomitant increase in intracellular FN. The effect of novobiocin was specific to LRP1-expressing cells and could be recapitulated by an LRP1 blocking antibody and the allosteric C-terminal Hsp90 inhibitor SM253, but not the N-terminal inhibitor geldanamycin. Together these data suggest that LRP1 is required for FN turnover in response to Hsp90 inhibition by novobiocin, which may have unintended physiological consequences in contexts where C-terminal Hsp90 inhibition is to be used therapeutically.
Expressed HNSCC variants by HPV-status in a well-characterized Michigan cohort
Authors: Qin Tingting , Zhang Yanxiao , Zarins Katie R. , Jones Tamara R. , Virani Shama , Peterson Lisa A. , McHugh Jonathan B. , Chepeha Douglas , Wolf Gregory T. , Rozek Laura S. , Sartor Maureen A.
Published: July 2018

While whole-exome DNA sequencing is the most common technology to study genetic variants in tumors in known exonic regions, RNA-seq is cheaper, covers most of the same exonic regions, and is often more readily available. In this study, we show the utility of mRNA-seq-based variant analysis combined with targeted gene sequencing performed on both tumor and matched blood as an alternative when exome data is unavailable. We use the approach to study expressed variant profiles in the well-characterized University of Michigan (UM) head and neck squamous carcinoma (HNSCC) cohort (n = 36). We found that 441 out of 455 (~97%) identified cancer genes with an expressed variant in the UM cohort also harbor a somatic mutation in TCGA. Fourteen (39%) patients had a germline variant in a cancer-related Fanconi Anemia (FA) pathway gene. HPV-positive patients had more nonsynonymous, rare, and damaging (NRD) variants in those genes than HPV-negative patients. Moreover, the known mutational signatures for DNA mismatch repair and APOBEC activation were attributive to the UM expressed NRD variants, and the APOBEC signature contribution differed by HPV status. Our results provide additional support to certain TCGA findings and suggest an association of expressed variants in FA/DNA repair pathways with HPV-associated HNSCC tumorigenesis. These results will benefit future studies on this and other cohorts by providing the genetic variants of key cancer-related genes.
Experimental Demonstration of a Spin Logic Device with Deterministic and Stochastic Mode of Operation
Authors: Debashis Punyashloka , Chen Zhihong
Published: July 2018

Spin based logic devices have attracted a lot of research interest due to their potential low-power operation, non-volatility and possibility to enable new computing applications. Here we present an experimental demonstration of a novel spin logic device working at room temperature without the requirement of an external magnetic field. Our device is based on a pair of coupled in-plane magnetic anisotropy (IMA) magnet and a perpendicular magnetic anisotropy (PMA) magnet. The information written in the state of the IMA magnet is transferred to the state of the PMA magnet by means of a symmetry breaking dipolar field, while the two layers are electrically isolated. In addition to having the basic tenets of a logic device, our device has inbuilt memory, taking advantage of the non-volatility of nanomagnets. In another mode of operation, the same device is shown to have the functionality of a true random number generator (TRNG). The combination of logic functionality, nonvolatility and capability to generate true random numbers all in the same spin logic device, makes it uniquely suitable as a hardware for many new computing ideas.