bluuebunny/crossref_metadata_2025 huggingface dataset:
Is the Era of Work Coming to an End?Erasmus Lecture delivered at the Budapest meeting of the Academia Europaea, 5 September 2017
Authors: Mas-Colell Andreu
Published: October 2018

The question in the title is examined from the standpoint of economic thinking. Three ideas are sustained: (1) if made an objective of economic policy, the necessity of work could be minimized in the distant future; (2) this is not what is desirable or will tend to happen. Even in extreme scenarios of robot adoption considerable demand for human labor should persist in tasks related to the expansion of the knowledge frontier and in those where the humanity of the executor is of the essence for the definition of the task (performing, sports, care, companionship, and so on); (3) redistributive taxation may well be in order. Guaranteed income schemes, and the link with entitlement through work, are discussed.
Follow the footprints and mind the gaps: a new look at the origin of tetrapods
Authors: AHLBERG Per E.
Published: October 2018

The hypothesis that tetrapods evolved from elpistostegids during the Frasnian, in a predominantly aquatic context, has been challenged by the discovery of Middle Devonian tetrapod trackways predating the earliest body fossils of both elpistostegids and tetrapods. Here I present a new hypothesis based on an overview of the trace fossil and body fossil evidence. The trace fossils demonstrate that tetrapods were capable of performing subaerial lateral sequence walks before the end of the Middle Devonian. The derived morphological characters of elpistostegids and Devonian tetrapods are related to substrate locomotion, weight support and aerial vision, and thus to terrestrial competence, but the retention of lateral-line canals, gills and fin rays shows that they remained closely tied to the water. Elpistostegids and tetrapods both evolved no later than the beginning of the Middle Devonian. The earliest tetrapod records come from inland river basins, sabkha plains and ephemeral coastal lakes that preserve few, if any, body fossils; contemporary elpistostegids occur in deltas and the lower reaches of permanent rivers where body fossils are preserved. During the Frasnian, elpistostegids disappear and these riverine-deltaic environments are colonised by tetrapods. This replacement has, in the past, been misinterpreted as the origin of tetrapods.
Development and Assessment of the Atmospheric Pressure Vertical Correction Model With ERA‐Interim and Radiosonde Data
Authors: Yao Yibin , Sun Zhangyu , Xu Chaoqian , Zhang Liang , Wan Yangyang
Published: October 2018

Atmospheric pressure is a critical parameter in Global Navigation Satellite System (GNSS) technology to calculate zenith hydrostatic delay (ZHD). Because the reference pressure is usually not at the height of the GNSS receiving antenna, a vertical correction of the pressure value is inevitable. This paper used the ERA‐Interim data to develop a grid model for such correction by introducing a new parameter. Then, the ERA‐Interim and radiosonde data were employed for assessing the newly built model along with other two types of state‐of‐art vertical correction methods (which are named as the virtual temperature (Tv)‐based model and the temperature (T0)‐based model in this paper). Furthermore, the assessments were conducted in two cases where the measured meteorological data are available and unavailable. Results show that the Tv‐based model and the T0‐based model may have limitations in some ice‐covered regions (e.g. the Antarctica, the Qinghai‐Tibetan Plateau and the Greenland), but the grid model built in this paper does not show the weaknesses. For the results of the four different assessments devised in this paper (assessed with the ERA‐Interim or radiosonde data, with or without the measured meteorological data), the grid model always shows the highest precision among these three models, and the T0‐based model has higher accuracy than the Tv‐based model. Additionally, this paper found that when the height differences of the correction are large, the Tv‐based model may have large uncertainties while the grid model is still applicable.
Envelope Widths of Volcano‐Seismic Events and Seismic Scattering Characteristics Beneath Volcanoes
Authors: Kumagai Hiroyuki , Londoño John Makario , Maeda Yuta , López Velez Cristian Mauricio , Lacson Rudy
Published: October 2018

Volcanoes produce highly scattered seismic wavefields, which are characterized by the scattering mean free path (l0) and the quality factor of medium attenuation for S waves (Qi). Previous studies have estimated scattering mean free paths at various volcanoes to be around 100–1,000 m, but their depth distributions remain to be determined. We estimated one‐dimensional l0 and Qi structures using the envelope widths of volcano‐seismic events at Taal (Philippines) and at Nevado del Ruiz (Colombia) in a high‐frequency band (5–10 Hz). We performed Monte Carlo envelope simulations in various one‐dimensional models, and compared the simulated and observed envelope widths. Our results indicate that a highly heterogeneous (l0 = 1,000 m) and attenuative (Qi = 100) surface layer exists to a depth of 1 km, below which l0 and Qi are comparable to those in the normal crust. The surface layer may consist of unconsolidated materials with hydrothermal fluids and/or altered clay minerals, which cause strong scattering and attenuation effects beneath these volcanoes. Our results suggest that strong heterogeneities observed at volcanoes exist only in a thin surface layer.
Diffusion Creep and Grain Growth in Forsterite +20 vol% Enstatite Aggregates: 1. High‐Resolution Experiments and Their Data Analyses
Authors: Nakakoji T. , Hiraga T. , Nagao H. , Ito S. , Kano M.
Published: October 2018

We conducted uniaxial compression and grain growth experiments on fine‐grained (~1 μm) forsterite +20 vol% enstatite aggregates. Based on analyses of the sensitivity of the strain rate as a function of stress, we find power law creep at low stress, Newtonian creep at intermediate stress, and again power law creep at high stress, which correspond to interface‐controlled diffusion creep, grain boundary diffusion (Coble) creep, and a dislocation‐controlled process, respectively. The creep rate of these samples is well expressed by a combination of strain rates of these three mechanisms where interface‐controlled and Coble creep rates are combined as series‐sequential processes, while the rate of the dislocation process is added with them as a parallel‐concurrent process. Mechanical data collected continuously during the application of a constant load but while slowly changing temperature were decomposed into data for every 1 °C, which allowed consideration of >600 mechanical data points from 1054 to 1370 °C. The data were analyzed using Bayesian statistics implementing a Markov chain Monte Carlo method imposed on the above constitutive equation, resulting in the best fit flow law parameters for interface‐controlled and Coble creep. Samples were annealed for 500 hr at various temperatures. A comparison of the final grain sizes as a function of temperature on an Arrhenius plot resulted in an activation energy for grain growth similar to that observed for grain boundary diffusion during Coble creep of these materials.
Diffusion Creep and Grain Growth in Forsterite +20 vol% Enstatite Aggregates: 2. Their Common Diffusional Mechanism and Its Consequence for Weak‐Temperature‐Dependent Viscosity
Authors: Nakakoji T. , Hiraga T.
Published: October 2018

We determined the rate‐controlling diffusivities for creep and grain growth of forsterite +20 vol% enstatite aggregates from the experimental results presented in Part 1 of this study. Both diffusivities exhibit similar values with similar temperature dependency, indicating that a common grain boundary diffusion process controls both creep and grain growth. This correspondence is due to the presence of pyroxene grains as a secondary phase in the olivine aggregate, which is the case for the majority of mantle‐derived rocks. As a consequence, the viscosity (η) of the material during deformation by grain boundary diffusion creep accompanied by grain growth changes with time (t) and temperature (T) as
where QGB is the activation energy for grain boundary diffusion and R is gas constant. This viscosity relationship is used to interpret the very low activation energy estimated for the viscosity of the oceanic mantle lithosphere.
A Seasonally Recurrent Annular Cyclone in Mars Northern Latitudes and Observations of a Companion Vortex
Authors: Sánchez‐Lavega A. , Garro A. , del Río‐Gaztelurrutia T. , Hueso R. , Ordoñez‐Etxeberria I. , Chen Chen H. , Cardesín‐Moinelo A. , Titov D. , Wood S. , Almeida M. , Spiga A. , Forget F. , Määttänen A. , Hoffmann H. , Gondet B.
Published: October 2018

We study a seasonally recurrent cyclone and related cloud phenomena observed on Mars at Ls ~120°, latitude ~60°N, and longitude 90°W from images obtained with cameras in different spacecraft between 1995 and 2018. A remarkable double cyclone formed in 2012 and we present a detailed study of its dynamics using images from Mars Express and Mars Reconnaissance Orbiter obtained between 6 June and 9 July. A double cyclone was also observed in 2006 and 2008. In other Martian years the primary cyclone showed an annular cloud morphology with a large water ice cloud observed eastward of it. The cyclones have a size of ~600–800 km with a cloud‐free core of a radius ~100–300 km. Tangential velocities measured from cloud tracking in 2012 images are ~5–20 m/s−1 at 10‐km altitude and double cyclone moved eastward with a velocity of 4 m/s−1 during its lifetime of one month. The vortices grow in the morning hours, but with the increasing insolation as the sol progresses, a part of the clouds evaporate, the winds weaken, and the vortices lose coherence. This phenomenon forms under high‐temperature gradients in a region with a large north‐south topographic slope and has been recurrent each Martian year between 1995 and 2018. We argue the interest of studying its changing properties each Martian year in order to explore their possible relationship to the state of the Martian atmosphere at Ls ~120°.
miR4673 improves fitness profile of neoplastic cells by induction of autophagy
Authors: Dökümcü Kağan , Simonian Mary , Farahani Ramin M.
Published: October 2018

Therapeutic resistance of neoplasms is mainly attributed to gradual evolution of mutational profile1. Here, we demonstrate a microRNA-mediated mechanism that effectively improves fitness of SKBR3 mammary carcinoma cells by cytoplasmic reprogramming. The reprogramming is triggered by endogenous miR4673 transcribed from notch-1 locus. The miRNA downregulates cdk-18, a cyclin-dependent kinase that regulates M-G1 transition in cycling cells2,3. Suppression of cdk-18 triggers mitophagy and autophagy. Due to high autophagic flux, oestrogen receptor-1+/progesterone receptor+/p53+(Esr1+/Pr+/p53+) SKBR3 cells are coerced into an Esr1−/Prlow/p53−profile. Increased mitophagy in combination with proteasomal degradation of p53 transiently arrests the cycling cells at G0 and enhances radio-resistance of the SKBR3 population. These findings highlight the impact on cancer therapy of non-encoded neoplastic resistance, arising as a consequence of miRNA-mediated autophagic reprogramming that uncouples phenotype and genotype.
Cardiomyocyte gene programs encoding morphological and functional signatures in cardiac hypertrophy and failure
Authors: Nomura Seitaro , Satoh Masahiro , Fujita Takanori , Higo Tomoaki , Sumida Tomokazu , Ko Toshiyuki , Yamaguchi Toshihiro , Tobita Takashige , Naito Atsuhiko T. , Ito Masamichi , Fujita Kanna , Harada Mutsuo , Toko Haruhiro , Kobayashi Yoshio , Ito Kaoru , Takimoto Eiki , Akazawa Hiroshi , Morita Hiroyuki , Aburatani Hiroyuki , Komuro Issei
Published: October 2018

Pressure overload induces a transition from cardiac hypertrophy to heart failure, but its underlying mechanisms remain elusive. Here we reconstruct a trajectory of cardiomyocyte remodeling and clarify distinct cardiomyocyte gene programs encoding morphological and functional signatures in cardiac hypertrophy and failure, by integrating single-cardiomyocyte transcriptome with cell morphology, epigenomic state and heart function. During early hypertrophy, cardiomyocytes activate mitochondrial translation/metabolism genes, whose expression is correlated with cell size and linked to ERK1/2 and NRF1/2 transcriptional networks. Persistent overload leads to a bifurcation into adaptive and failing cardiomyocytes, and p53 signaling is specifically activated in late hypertrophy. Cardiomyocyte-specific p53 deletion shows that cardiomyocyte remodeling is initiated by p53-independent mitochondrial activation and morphological hypertrophy, followed by p53-dependent mitochondrial inhibition, morphological elongation, and heart failure gene program activation. Human single-cardiomyocyte analysis validates the conservation of the pathogenic transcriptional signatures. Collectively, cardiomyocyte identity is encoded in transcriptional programs that orchestrate morphological and functional phenotypes.
Mesopontine cholinergic inputs to midbrain dopamine neurons drive stress-induced depressive-like behaviors
Authors: Fernandez Sebastian P. , Broussot Loïc , Marti Fabio , Contesse Thomas , Mouska Xavier , Soiza-Reilly Mariano , Marie Hélène , Faure Philippe , Barik Jacques
Published: October 2018

Stressful life events are primary environmental factors that markedly contribute to depression by triggering brain cellular maladaptations. Dysregulation of ventral tegmental area (VTA) dopamine neurons has been causally linked to the appearance of social withdrawal and anhedonia, two classical manifestations of depression. However, the relevant inputs that shape these dopamine signals remain largely unknown. We demonstrate that chronic social defeat (CSD) stress, a preclinical paradigm of depression, causes marked hyperactivity of laterodorsal tegmentum (LDTg) excitatory neurons that project to the VTA. Selective chemogenetic-mediated inhibition of cholinergic LDTg neurons prevent CSD-induced VTA DA neurons dysregulation and depressive-like behaviors. Pro-depressant outcomes are replicated by pairing activation of LDTg cholinergic terminals in the VTA with a moderate stress. Prevention of CSD outcomes are recapitulated by blocking corticotropin-releasing factor receptor 1 within the LDTg. These data uncover a neuro-circuitry of depressive-like disorders and demonstrate that stress, via a neuroendocrine signal, profoundly dysregulates the LDTg.
Nanocardboard as a nanoscale analog of hollow sandwich plates
Authors: Lin Chen , Nicaise Samuel M. , Lilley Drew E. , Cortes Joan , Jiao Pengcheng , Singh Jaspreet , Azadi Mohsen , Lopez Gerald G. , Metzler Meredith , Purohit Prashant K. , Bargatin Igor
Published: October 2018

Corrugated paper cardboard provides an everyday example of a lightweight, yet rigid, sandwich structure. Here we present nanocardboard, a monolithic plate mechanical metamaterial composed of nanometer-thickness (25–400 nm) face sheets that are connected by micrometer-height tubular webbing. We fabricate nanocardboard plates of up to 1 centimeter-square size, which exhibit an enhanced bending stiffness at ultralow mass of ~1 g m−2. The nanoscale thickness allows the plates to completely recover their shape after sharp bending even when the radius of curvature is comparable to the plate height. Optimally chosen geometry enhances the bending stiffness and spring constant by more than four orders of magnitude in comparison to solid plates with the same mass, far exceeding the enhancement factors previously demonstrated at both the macroscale and nanoscale. Nanocardboard may find applications as a structural component for wings of microflyers or interstellar lightsails, scanning probe cantilevers, and other microscopic and macroscopic systems.
Long-term positioning and polar preference of chemoreceptor clusters in E. coli
Authors: Koler Moriah , Peretz Eliran , Aditya Chetan , Shimizu Thomas S. , Vaknin Ady
Published: October 2018

The bacterial chemosensory arrays are a notable model for studying the basic principles of receptor clustering and cellular organization. Here, we provide a new perspective regarding the long-term dynamics of these clusters in growing E. coli cells. We demonstrate that pre-existing lateral clusters tend to avoid translocation to pole regions and, therefore, continually shuttle between the cell poles for many generations while being static relative to the local cell-wall matrix. We also show that the polar preference of clusters results fundamentally from reduced clustering efficiency in the lateral region, rather than a developmental-like progression of clusters. Furthermore, polar preference is surprisingly robust to structural alterations designed to probe preference due to curvature sorting, perturbing the cell envelope physiology affects the cluster-size distribution, and the size-dependent mobility of receptor complexes differs between polar and lateral regions. Thus, distinct envelope physiology in the polar and lateral cell regions may contribute to polar preference.
Host suppression of quorum sensing during catheter-associated urinary tract infections
Authors: Cole Stephanie J. , Hall Cherisse L. , Schniederberend Maren , Farrow III John M. , Goodson Jonathan R. , Pesci Everett C. , Kazmierczak Barbara I. , Lee Vincent T.
Published: October 2018

Chronic bacterial infections on medical devices, including catheter-associated urinary tract infections (CAUTI), are associated with bacterial biofilm communities that are refractory to antibiotic therapy and resistant to host immunity. Previously, we have shown that Pseudomonas aeruginosa can cause CAUTI by forming a device-associated biofilm that is independent of known biofilm exopolysaccharides. Here, we show by RNA-seq that host urine alters the transcriptome of P. aeruginosa by suppressing quorum sensing regulated genes. P. aeruginosa produces acyl homoserine lactones (AHLs) in the presence of urea, but cannot perceive AHLs. Repression of quorum sensing by urine implies that quorum sensing should be dispensable during infection of the urinary tract. Indeed, mutants defective in quorum sensing are able to colonize similarly to wild-type in a murine model of CAUTI. Quorum sensing-regulated processes in clinical isolates are also inhibited by urea. These data show that urea in urine is a natural anti-quorum sensing mechanism in mammals.
Following hearts, one cell at a time: recent applications of single-cell RNA sequencing to the understanding of heart disease
Authors: Ackers-Johnson Matthew , Tan Wilson Lek Wen , Foo Roger Sik-Yin
Published: October 2018

The mammalian heart contains heterogeneous cell types contributing to pathological changes in cardiac disease. In this Comment, we explore how single-cell transcriptomic approaches are unveiling intricate cellular mechanisms and gene co-expression networks that regulate the workings, and failings, of the heart.
Contribution of epigenetic variation to adaptation in Arabidopsis
Authors: Schmid Marc W. , Heichinger Christian , Coman Schmid Diana , Guthörl Daniela , Gagliardini Valeria , Bruggmann Rémy , Aluri Sirisha , Aquino Catharine , Schmid Bernhard , Turnbull Lindsay A. , Grossniklaus Ueli
Published: October 2018

In plants, transgenerational inheritance of some epialleles has been demonstrated but it remains controversial whether epigenetic variation is subject to selection and contributes to adaptation. Simulating selection in a rapidly changing environment, we compare phenotypic traits and epigenetic variation between Arabidopsis thaliana populations grown for five generations under selection and their genetically nearly identical ancestors. Selected populations of two distinct genotypes show significant differences in flowering time and plant architecture, which are maintained for at least 2–3 generations in the absence of selection. While we cannot detect consistent genetic changes, we observe a reduction of epigenetic diversity and changes in the methylation state of about 50,000 cytosines, some of which are associated with phenotypic changes. Thus, we propose that epigenetic variation is subject to selection and can contribute to rapid adaptive responses, although the extent to which epigenetics plays a role in adaptation is still unclear.
Adhesion to nanofibers drives cell membrane remodeling through one-dimensional wetting
Authors: Charles-Orszag Arthur , Tsai Feng-Ching , Bonazzi Daria , Manriquez Valeria , Sachse Martin , Mallet Adeline , Salles Audrey , Melican Keira , Staneva Ralitza , Bertin Aurélie , Millien Corinne , Goussard Sylvie , Lafaye Pierre , Shorte Spencer , Piel Matthieu , Krijnse-Locker Jacomine , Brochard-Wyart Françoise , Bassereau Patricia , Duménil Guillaume
Published: October 2018

The shape of cellular membranes is highly regulated by a set of conserved mechanisms that can be manipulated by bacterial pathogens to infect cells. Remodeling of the plasma membrane of endothelial cells by the bacterium Neisseria meningitidis is thought to be essential during the blood phase of meningococcal infection, but the underlying mechanisms are unclear. Here we show that plasma membrane remodeling occurs independently of F-actin, along meningococcal type IV pili fibers, by a physical mechanism that we term ‘one-dimensional’ membrane wetting. We provide a theoretical model that describes the physical basis of one-dimensional wetting and show that this mechanism occurs in model membranes interacting with nanofibers, and in human cells interacting with extracellular matrix meshworks. We propose one-dimensional wetting as a new general principle driving the interaction of cells with their environment at the nanoscale that is diverted by meningococci during infection.
Phase-controlled Fourier-transform spectroscopy
Authors: Hashimoto Kazuki , Ideguchi Takuro
Published: October 2018

Fourier-transform spectroscopy (FTS) has been widely used as a standard analytical technique over the past half-century. FTS is an autocorrelation-based technique that is compatible with both temporally coherent and incoherent light sources, and functions as an active or passive spectrometer. However, it has been mostly used for static measurements due to the low scan rate imposed by technological restrictions. This has impeded its application to continuous rapid measurements, which would be of significant interest for a variety of fields, especially when monitoring of non-repeating or transient complex dynamics is desirable. Here, we demonstrate highly efficient FTS operating at a high spectral acquisition rate with a simple delay line based on a dynamic phase-control technique. The independent adjustability of phase and group delays allows us to achieve the Nyquist-limited spectral acquisition rate over 10,000 spectra per second, while maintaining a large spectral bandwidth and high resolution. We also demonstrate passive spectroscopy with an incoherent light source.
Enabling nanoscale flexoelectricity at extreme temperature by tuning cation diffusion
Authors: Molina-Luna Leopoldo , Wang Shuai , Pivak Yevheniy , Zintler Alexander , Pérez-Garza Héctor H. , Spruit Ronald G. , Xu Qiang , Yi Min , Xu Bai-Xiang , Acosta Matias
Published: October 2018

Any dielectric material under a strain gradient presents flexoelectricity. Here, we synthesized 0.75 sodium bismuth titanate −0.25 strontium titanate (NBT-25ST) core–shell nanoparticles via a solid-state chemical reaction directly inside a transmission electron microscope (TEM) and observed domain-like nanoregions (DLNRs) up to an extreme temperature of 800 °C. We attribute this abnormal phenomenon to a chemically induced lattice strain gradient present in the core–shell nanoparticle. The strain gradient was generated by controlling the diffusion of strontium cations. By combining electrical biasing and temperature-dependent in situ TEM with phase field simulations, we analyzed the resulting strain gradient and local polarization distribution within a single nanoparticle. The analysis confirms that a local symmetry breaking, occurring due to a strain gradient (i.e. flexoelectricity), accounts for switchable polarization beyond the conventional temperature range of existing polar materials. We demonstrate that polar nanomaterials can be obtained through flexoelectricity at extreme temperature by tuning the cation diffusion.
Rewriting the phase diagram of a diamagnetic liquid crystal by a magnetic field
Authors: Hajjaj Fatin , Kajitani Takashi , Ohsumi Hiroyuki , Tanaka Yoshikazu , Kato Kenichi , Takata Masaki , Kitazawa Hideaki , Arima Taka-hisa , Aida Takuzo , Fukushima Takanori
Published: October 2018

Magnetic fields have been considered to only interact with organic materials non-destructively, leaving their fundamental structures unaffected, even when a strong magnetic field generated from a superconducting magnet is applied. Here we report an unprecedented observation that a liquid-crystalline mesophase of a diamagnetic molecular assembly with an orthorhombic or a cubic structure is formed selectively in the absence or presence of a strong magnetic field. The constituent molecule is a triphenylene derivative carrying six imidazolium bromide-terminated alkyl side chains and exhibits a cubic, orthorhombic, or hexagonal columnar mesophase when complexed with an appropriate amount of lanthanum(III) bromide. Thermal processing of the La3+-containing liquid-crystalline assembly in the presence of a 10-tesla magnetic field resulted in a phase diagram, in which the orthorhombic phase is completely replaced with the cubic phase. The discovery of this magneto-induced phase-selection offers an insight into the interactions between magnetic fields and organic material.
Self-implantable double-layered micro-drug-reservoirs for efficient and controlled ocular drug delivery
Authors: Than Aung , Liu Chenghao , Chang Hao , Duong Phan Khanh , Cheung Chui Ming Gemmy , Xu Chenjie , Wang Xiaomeng , Chen Peng
Published: October 2018

Eye diseases and injuries impose a significant clinical problem worldwide. Safe and effective ocular drug delivery is, however, challenging due to the presence of ocular barriers. Here we report a strategy using an eye patch equipped with an array of detachable microneedles. These microneedles can penetrate the ocular surface tissue, and serve as implanted micro-reservoirs for controlled drug delivery. The biphasic drug release kinetics enabled by the double-layered micro-reservoirs largely enhances therapeutic efficacy. Using corneal neovascularization as the disease model, we show that delivery of an anti-angiogenic monoclonal antibody (DC101) by such eye patch produces ~90% reduction of neovascular area. Furthermore, quick release of an anti-inflammatory compound (diclofenac) followed by a sustained release of DC101 provides synergistic therapeutic outcome. The eye patch application is easy and minimally invasive to ensure good patient compliance. Such intraocular drug delivery strategy promises effective home-based treatment of many eye diseases.
Diagnostic value of signs, symptoms and diagnostic tests for diagnosing pneumonia in ambulant children in developed countries: a systematic review
Authors: Schot Marjolein J. C. , Dekker Anne R. J. , Giorgi Wesley G. , Hopstaken Rogier M. , de Wit Niek J. , Verheij Theo J. M. , Cals Jochen W. L.
Published: October 2018

Identifying a child with pneumonia in the large group of children with acute respiratory tract infections can be challenging for primary care physicians. Knowledge on the diagnostic value of specific signs and symptoms may guide future decision rules and guidelines for clinicians. We aimed to identify and systematically review available evidence for the diagnostic value of signs, symptoms, and additional tests to diagnose pneumonia in children in an ambulatory setting in developed countries. We conducted a systematic review, searching in the electronic databases of PubMed and Embase. Quality assessment of studies was done using the QUADAS-2 criteria. After data extraction from selected studies, we calculated and summarized test characteristics (sensitivity, specificity, negative and positive predictive values) of all available signs, symptoms, additional laboratory tests, and chest ultrasonography. The original search yielded 4665 records, of which 17 articles were eligible for analysis: 12 studies on signs and symptoms, 4 on additional laboratory tests, and 6 on ultrasonography. All included studies were performed in a secondary care setting. Risk of bias was present in the majority of studies in the domain of patient selection. Prevalence of pneumonia varied from 3.4% to 71.7%. The diagnostic value of the available 27 individual signs and symptoms to identify pneumonia was low. In a low prevalence setting, (4 studies, pneumonia prevalence <10%) clinically ill appearance of the child and oxygen saturation <94% can aid a physician. In a high prevalence setting (10 studies, pneumonia >10%), additional diagnostic tests such as oxygen saturation, C-reactive protein, and white blood cell count are more promising. Chest ultrasonography showed high diagnostic value in settings with higher prevalence of pneumonia. Single signs and symptoms from medical history and physical examination or individual additional diagnostic tests are insufficient to diagnose pneumonia in ambulant children. Very few diagnostic studies are conducted in settings with low prevalence of pneumonia. Future research in low prevalence settings should focus on the diagnostic value of the combination of clinical features and additional testing possibly using meta-analysis of individual data.
Reversible magnetic switching of high-spin molecules on a giant Rashba surface
Authors: Kügel Jens , Karolak Michael , Krönlein Andreas , Serrate David , Bode Matthias , Sangiovanni Giorgio
Published: October 2018

The quantum mechanical screening of a spin via conduction electrons depends sensitively on the environment seen by the magnetic impurity. A high degree of responsiveness can be obtained with metal complexes, as the embedding of a metal ion into an organic molecule prevents intercalation or alloying and allows for a good control by an appropriate choice of the ligands. There are therefore hopes to reach an “on demand” control of the spin state of single molecules adsorbed on substrates. Hitherto one route was to rely on “switchable” molecules with intrinsic bistabilities triggered by external stimuli, such as temperature or light, or on the controlled dosing of chemicals to form reversible bonds. However, these methods constrain the functionality to switchable molecules or depend on access to atoms or molecules. Here, we present a way to induce bistability also in a planar molecule by making use of the environment. We found that the particular “habitat” offered by an antiphase boundary of the Rashba system BiAg2 stabilizes a second structure for manganese phthalocyanine molecules, in which the central Mn ion moves out of the molecular plane. This corresponds to the formation of a large magnetic moment and a concomitant change of the ground state with respect to the conventional adsorption site. The reversible spin switch found here shows how we can not only rearrange electronic levels or lift orbital degeneracies via the substrate, but even sway the effects of many-body interactions in single molecules by acting on their surrounding.
Beneficial effects of intravenous iron therapy in a rat model of heart failure with preserved systemic iron status but depleted intracellular cardiac stores
Authors: Paterek Aleksandra , Kępska Marta , Sochanowicz Barbara , Chajduk Ewelina , Kołodziejczyk Joanna , Polkowska-Motrenko Halina , Kruszewski Marcin , Leszek Przemysław , Mackiewicz Urszula , Mączewski Michał
Published: October 2018

Iron deficiency (ID) commonly occurs in chronic heart failure (HF) and is associated with poor prognosis. Neither its causes nor pathophysiological significance are clearly understood. We aimed to assess iron status and the effect of iron supplementation in the rat model of post-myocardial infarction (MI) HF. Four weeks after induction of MI to induce HF or sham surgery, rats received intravenous iron (ferric carboxymaltose) or saline, 4 doses in 1-week intervals. HF alone did not cause anemia, systemic or myocardial ID, but reduced myocardial ferritin, suggesting depleted cardiomyocyte iron stores. Iron therapy increased serum Fe, ferritin and transferrin saturation as well as cardiac and hepatic iron content in HF rats, but did not increase myocardial ferritin. This was accompanied by: (1) better preservation of left ventricular (LV) ejection fraction and smaller LV dilation, (2) preservation of function of Ca2+ handling proteins in LV cardiomyocytes and (3) reduced level of inflammatory marker, CRP. Furthermore, iron supplementation did not potentiate oxidative stress or have toxic effects on cardiomyocyte function, but increased activity of antioxidant defenses (cardiac superoxide dismutase). Despite lack of systemic or myocardial ID we found evidence of depleted cardiomyocyte iron stores in the rat model of HF. Furthermore we observed positive effect of iron supplementation and confirmed safety of iron supplementation in this setting.
Effectiveness and safety of self-managed oral anticoagulant therapy compared with direct oral anticoagulants in patients with atrial fibrillation
Authors: Grove Erik Lerkevang , Skjøth Flemming , Nielsen Peter Brønnum , Christensen Thomas Decker , Larsen Torben Bjerregaard
Published: October 2018

We compared the effectiveness and safety of direct oral anticoagulants (DOAC) vs patient self-managed warfarin therapy (PSM) in patients with atrial fibrillation. We linked prospectively registered data from university hospital clinics to nationwide Danish health registries. Primary effectiveness and safety outcomes were ischaemic stroke (incl. systemic embolism) and major bleeding. All-cause mortality and all-cause stroke were secondary outcomes. An inverse probability of treatment propensity-weighted approach was applied to adjust for potential confounding. The study cohorts included 534 patients treated with PSM and 2,671 patients treated with DOAC. Weighted rates of ischaemic stroke were 0.46 and 1.30 percent per year with PSM vs DOAC, hazard ratio (HR) 0.27 (95% confidence interval 0.11–0.68) with 2.5 years follow-up. Rates of major bleeding were 2.32 and 2.13 percent per year (HR 1.06 [0.69–1.63]). All-cause mortality was not statistically different (HR 0.67 [0.39–1.17]), whereas the incidence of all-cause stroke was significantly lower among patients treated with PSM with rates of 0.61 vs 1.45 percent per year (HR 0.36 [0.16–0.78]). In patients with atrial fibrillation, self-managed oral anticoagulant treatment was associated with a significantly lower risk of all-cause and ischaemic stroke compared to treatment with DOAC, whereas no significant differences were observed for major bleeding and mortality.
Previous antiretroviral drug use compromises standard first-line HIV therapy and is mediated through drug-resistance
Authors: Inzaule Seth C. , Kityo Cissy M. , Siwale Margaret , Akanmu Alani Sulaimon , Wellington Maureen , de Jager Marleen , Ive Prudence , Mandaliya Kishor , Stevens Wendy , Boender T. Sonia , Ondoa Pascale , Sigaloff Kim C. E. , Naniche Denise , Rinke de Wit Tobias F. , Hamers Raph L.
Published: October 2018

In ART programs in sub-Saharan Africa, a growing proportion of HIV-infected persons initiating first-line antiretroviral therapy (ART) have a history of prior antiretroviral drug use (PAU). We assessed the effect of PAU on the risk of pre-treatment drug resistance (PDR) and virological failure (VF) in a multicountry cohort of HIV-infected adults initiated on a standard non-nucleoside reverse transcriptase inhibitor (NNRTI)-based first-line ART. Multivariate logistic regression was used to assess the associations between PAU, PDR and VF (defined as viral load ≥400 cps/mL). Causal mediation analysis was used to assess the proportion of the effect of PAU on VF that could be eliminated by intervening on PDR. Of 2737 participants, 122 (4.5%) had a history of PAU. Participants with PAU had a 7.2-fold (95% CI 4.4–11.7) risk of carrying PDR and a 3.1-fold (95% CI 1.6–6.1) increased risk of VF, compared to antiretroviral-naïve participants. Controlling for PDR would eliminate nearly half the effect of PAU on the risk of VF. Patients with a history of PAU are at increased risk of ART failure, which is to a large extent attributable to PDR. These findings support the recent WHO recommendations for use of differentiated, non-NNRTI-based empiric first-line therapy in patients with PAU.
Whole genome sequencing for investigations of meningococcal outbreaks in the United States: a retrospective analysis
Authors: Whaley Melissa J. , Joseph Sandeep J. , Retchless Adam C. , Kretz Cecilia B. , Blain Amy , Hu Fang , Chang How-Yi , Mbaeyi Sarah A. , MacNeil Jessica R. , Read Timothy D. , Wang Xin
Published: October 2018

Although rare in the U.S., outbreaks due to Neisseria meningitidis do occur. Rapid, early outbreak detection is important for timely public health response. In this study, we characterized U.S. meningococcal isolates (N = 201) from 15 epidemiologically defined outbreaks (2009–2015) along with temporally and geographically matched sporadic isolates using multilocus sequence typing, pulsed-field gel electrophoresis (PFGE), and six whole genome sequencing (WGS) based methods. Recombination-corrected maximum likelihood (ML) and Bayesian phylogenies were reconstructed to identify genetically related outbreak isolates. All WGS analysis methods showed high degree of agreement and distinguished isolates with similar or indistinguishable PFGE patterns, or the same strain genotype. Ten outbreaks were caused by a single strain; 5 were due to multiple strains. Five sporadic isolates were phylogenetically related to 2 outbreaks. Analysis of 9 outbreaks using timed phylogenies identified the possible origin and estimated the approximate time that the most recent common ancestor emerged for outbreaks analyzed. U.S. meningococcal outbreaks were caused by single- or multiple-strain introduction, with organizational outbreaks mainly caused by a clonal strain and community outbreaks by divergent strains. WGS can infer linkage of meningococcal cases when epidemiological links are uncertain. Accurate identification of outbreak-associated cases requires both WGS typing and epidemiological data.
Composite topological structure of domain walls in synthetic antiferromagnets
Authors: Kolesnikov A. G. , Plotnikov V. S. , Pustovalov E. V. , Samardak A. S. , Chebotkevich L. A. , Ognev A. V. , Tretiakov Oleg A.
Published: October 2018

We experimentally study the structure and dynamics of magnetic domains in synthetic antiferromagnets based on Co/Ru/Co films. Dramatic effects arise from the interaction among the topological defects comprising the dual domain walls in these structures. Under applied magnetic fields, the dual domain walls propagate following the dynamics of bi-meronic (bi-vortex/bi-antivortex) topological defects built in the walls. Application of an external field triggers a rich dynamical response: The propagation depends on mutual orientation and chirality of bi-vortices and bi-antivortices in the domain walls. For certain configurations, we observe sudden jumps of composite domain walls in increasing field, which are associated with the decay of composite skyrmions. These features allow for the enhanced control of domain-wall motion in synthetic antiferromagnets with the potential of employing them as information carriers in future logic and storage devices.
Syncope in haemodynamically stable and unstable patients with acute pulmonary embolism – Results of the German nationwide inpatient sample
Authors: Keller Karsten , Hobohm Lukas , Münzel Thomas , Ostad Mir Abolfazl , Espinola-Klein Christine
Published: October 2018

Syncope in pulmonary embolism (PE) could be the first sign of haemodynamic compromise. We aimed to investigate pathomechanisms of syncope and its impact on mortality. For this study, patients (aged ≥ 18years) were selected by screening the German nationwide inpatient sample for PE and stratified included patients by syncope (2011–2014). We analysed predictors of syncope in haemodynamically stable PE. Impact of syncope on in-hospital mortality in haemodynamically stable and unstable PE and benefit of systemic thrombolysis in haemodynamically stable PE with syncope (PE + Syncope) were analyzed. The German nationwide inpatient sample comprised 293,640 (84.9%) haemodynamically stable and 52,249 (15.1%) unstable PE patients; among them 2.3% had syncope. Right ventricular dysfunction (RVD) was a key predictor for syncope. In-hospital mortality-rate was lower in haemodynamically stable (6.4% vs. 7.6%, P < 0.001) and unstable PE + Syncope than in PE−Syncope (48.4% vs. 55.5%, P < 0.001) with reduced risk for in-hospital death in stable (OR 0.68 (95%CI 0.61–0.75), P < 0.001) and unstable (OR 0.69 (95% CI 0.62–0.78), P < 0.001) inpatients independent of age and sex. Haemodynamically stable PE + Syncope patients were more often treated with systemic thrombolysis (3.1% vs. 2.1%, P < 0.001). Systemic thrombolysis was associated with reduced in-hospital mortality in haemodynamically stable PE + Syncope (1.9% vs. 6.6%, P = 0.004) independently of age, RVD and tachycardia (OR 0.30 (95%CI 0.11–0.82), P = 0.019). In conclusion, in-hospital mortality was 6.4% in haemodynamically stable PE + Syncope. Haemodynamically stable PE + Syncope patients were more often treated with systemic thrombolysis and showed a trend to improved survial.
Peri-personal space as a prior in coupling visual and proprioceptive signals
Authors: Noel Jean-Paul , Samad Majed , Doxon Andrew , Clark Justin , Keller Sean , Di Luca Massimiliano
Published: October 2018

It has been suggested that the integration of multiple body-related sources of information within the peri-personal space (PPS) scaffolds body ownership. However, a normative computational framework detailing the functional role of PPS is still missing. Here we cast PPS as a visuo-proprioceptive Bayesian inference problem whereby objects we see in our environment are more likely to engender sensations as they come near to the body. We propose that PPS is the reflection of such an increased a priori probability of visuo-proprioceptive coupling that surrounds the body. To test this prediction, we immersed participants in a highly realistic virtual reality (VR) simulation of their right arm and surrounding environment. We asked participants to perform target-directed reaches toward visual, proprioceptive, and visuo-proprioceptive targets while visually displaying their reaching arm (body visible condition) or not (body invisible condition). Reach end-points are analyzed in light of the coupling prior framework, where the extension of PPS is taken to be represented by the spatial dispersion of the coupling prior between visual and proprioceptive estimates of arm location. Results demonstrate that if the body is not visible, the spatial dispersion of the visuo-proprioceptive coupling relaxes, whereas the strength of coupling remains stable. By demonstrating a distance-dependent alteration in visual and proprioceptive localization attractive pull toward one another (stronger pull at small spatial discrepancies) when the body is rendered invisible – an effect that is well accounted for by the visuo-proprioceptive coupling prior – the results suggest that the visible body grounds visuo-proprioceptive coupling preferentially in the near vs. far space.
Anisotropy in the magnetic interaction and lattice-orbital coupling of single crystal Ni3TeO6
Authors: Ghosh Anirudha , Chen K.-H. , Qiu X.-S. , Hsieh S. H. , Shao Y. C. , Du C. H. , Wang H. T. , Chin Y. Y. , Chiou J. W. , Ray Sekhar C. , Tsai H. M. , Pao C. W. , Lin H. J. , Lee J. F. , Sankar Raman , Chou F. C. , Pong W. F.
Published: October 2018

This investigation reports on anisotropy in the magnetic interaction, lattice-orbital coupling and degree of phonon softening in single crystal Ni3TeO6 (NTO) using temperature- and polarization-dependent X-ray absorption spectroscopic techniques. The magnetic field-cooled and zero-field-cooled measurements and temperature-dependent Ni L3,2-edge X-ray magnetic circular dichroism spectra of NTO reveal a weak Ni-Ni ferromagnetic interaction close to ~60 K (TSO: temperature of the onset of spin ordering) with a net alignment of Ni spins (the uncompensated components of the Ni moments) along the crystallographic c-axis, which is absent from the ab-plane. Below the Néel temperature, TN~ 52 K, NTO is stable in the antiferromagnetic state with its spin axis parallel to the c-axis. The Ni L3,2-edge X-ray linear dichroism results indicate that above TSO, the Ni 3d eg electrons preferentially occupy the out-of-plane 3d3z2−r2 orbitals and switch to the in-plane 3dx2−y2 orbitals below TSO. The inherent distortion of the NiO6 octahedra and anisotropic nearest-neighbor Ni-O bond lengths between the c-axis and the ab-plane of NTO, followed by anomalous Debye-Waller factors and orbital-lattice in conjunction with spin-phonon couplings, stabilize the occupied out-of-plane (3d3z2−r2) and in-plane (3dx2−y2) Ni eg orbitals above and below TSO, respectively.
Void structure stability in wet granular matter and its application to crab burrows and cometary pits
Authors: Shinoda Ayuko , Fujiwara Shin-ichi , Niiya Hirofumi , Katsuragi Hiroaki
Published: October 2018

Cohesive granular matter can support stable void structures, which can universally be found in various scenes from everyday lives to space. To quantitatively characterize the stability and strength of a void structure in cohesive granular matter, we perform a simple tunnel-compression experiment with wet granular matter. In the experiment, a horizontal tunnel in a wet granular layer is vertically compressed with a slow compression rate. The experimental result suggests that the tunnel deformation can be classified into the following three types: (i) shrink, (ii) shrink with collapse, and (iii) subsidence by collapse. Using the experimental result, we estimate the stable limit of various void structures in a cohesive granular layer from crab burrows on a sandy beach to the pits observed on cometary surfaces.
Identification of Novel Genes in Human Airway Epithelial Cells associated with Chronic Obstructive Pulmonary Disease (COPD) using Machine-Based Learning Algorithms
Authors: Mostafaei Shayan , Kazemnejad Anoshirvan , Azimzadeh Jamalkandi Sadegh , Amirhashchi Soroush , Donnelly Seamas C. , Armstrong Michelle E. , Doroudian Mohammad
Published: October 2018

The aim of this project was to identify candidate novel therapeutic targets to facilitate the treatment of COPD using machine-based learning (ML) algorithms and penalized regression models. In this study, 59 healthy smokers, 53 healthy non-smokers and 21 COPD smokers (9 GOLD stage I and 12 GOLD stage II) were included (n = 133). 20,097 probes were generated from a small airway epithelium (SAE) microarray dataset obtained from these subjects previously. Subsequently, the association between gene expression levels and smoking and COPD, respectively, was assessed using: AdaBoost Classification Trees, Decision Tree, Gradient Boosting Machines, Naive Bayes, Neural Network, Random Forest, Support Vector Machine and adaptive LASSO, Elastic-Net, and Ridge logistic regression analyses. Using this methodology, we identified 44 candidate genes, 27 of these genes had been previously been reported as important factors in the pathogenesis of COPD or regulation of lung function. Here, we also identified 17 genes, which have not been previously identified to be associated with the pathogenesis of COPD or the regulation of lung function. The most significantly regulated of these genes included: PRKAR2B, GAD1, LINC00930 and SLITRK6. These novel genes may provide the basis for the future development of novel therapeutics in COPD and its associated morbidities.