725 research outputs found

    Regional astrocyte IFN signaling restricts pathogenesis during neurotropic viral infection

    Get PDF
    Type I IFNs promote cellular responses to viruses, and IFN receptor (IFNAR) signaling regulates the responses of endothelial cells of the blood-brain barrier (BBB) during neurotropic viral infection. However, the role of astrocytes in innate immune responses of the BBB during viral infection of the CNS remains to be fully elucidated. Here, we have demonstrated that type I IFNAR signaling in astrocytes regulates BBB permeability and protects the cerebellum from infection and immunopathology. Mice with astrocyte-specific loss of IFNAR signaling showed decreased survival after West Nile virus infection. Accelerated mortality was not due to expanded viral tropism or increased replication. Rather, viral entry increased specifically in the hindbrain of IFNAR-deficient mice, suggesting that IFNAR signaling critically regulates BBB permeability in this brain region. Pattern recognition receptors and IFN-stimulated genes had higher basal and IFN-induced expression in human and mouse cerebellar astrocytes than did cerebral cortical astrocytes, suggesting that IFNAR signaling has brain region–specific roles in CNS immune responses. Taken together, our data identify cerebellar astrocytes as key responders to viral infection and highlight the existence of distinct innate immune programs in astrocytes from evolutionarily disparate regions of the CNS

    The Phanerozoic Record of Global Sea-Level Change

    Get PDF
    We review Phanerozoic sea-level changes [543 million years ago (Ma) to the present] on various time scales and present a new sea-level record for the past 100 million years (My). Long-term sea level peaked at 100 ± 50 meters during the Cretaceous, implying that ocean-crust production rates were much lower than previously inferred. Sea level mirrors oxygen isotope variations, reflecting ice-volume change on the 104- to 106-year scale, but a link between oxygen isotope and sea level on the 107-year scale must be due to temperature changes that we attribute to tectonically controlled carbon dioxide variations. Sea-level change has influenced phytoplankton evolution, ocean chemistry, and the loci of carbonate, organic carbon, and siliciclastic sediment burial. Over the past 100 My, sea-level changes reflect global climate evolution from a time of ephemeral Antarctic ice sheets (100 to 33 Ma), through a time of large ice sheets primarily in Antarctica (33 to 2.5 Ma), to a world with large Antarctic and large, variable Northern Hemisphere ice sheets (2.5 Ma to the present)

    Thermographic Detection of Delaminations in Laminated Structures

    Get PDF
    The detection of disbonds in a laminated structure is the focus of many nondestructive techniques.One of the promising techniques is thermography, where heat is applied to a structure, and the subsequent temperature profiles are detected with an infrared (IR) imager.If there is an even application of heat, an elevated temperature profile will appear, as a result of the reduction in heat flow from the surface layer to subsurface layers.Two advantages of the thermographic technique over more conventional ultrasonic techniques are that it can be easily made noncontacting and that large areas can be inspected in a short period of time

    Determination of the chemical environment of sulphur in petroleum asphaltenes by X-ray absorption spectroscopy

    Full text link
    Sulphur K-edge X-ray absorption spectra are analysed for a diverse series of petroleum asphaltenes. The spectra of the asphaltenes are interpreted by fitting with a linear superposition of model compound spectra. This analysis procedure is shown to work quite well in a stringent test case. The reduced forms of sulphur, thiophenes and sulphides dominate in all of the asphaltenes. Generally, the sulphoxide group is the most dominant form of the oxidized sulphur. Comparison of the X-ray data with the elemental composition of the asphaltenes shows that the sulphur and oxygen are preferentially bonded to each other. The inverse dependence of the oxygen-sulphur correlation with the fraction of sulphur which is sulphide suggests that oxidation of sulphur occurs preferentially at the sulphide group.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/30280/1/0000681.pd

    Research and Education in Computational Science and Engineering

    Get PDF
    Over the past two decades the field of computational science and engineering (CSE) has penetrated both basic and applied research in academia, industry, and laboratories to advance discovery, optimize systems, support decision-makers, and educate the scientific and engineering workforce. Informed by centuries of theory and experiment, CSE performs computational experiments to answer questions that neither theory nor experiment alone is equipped to answer. CSE provides scientists and engineers of all persuasions with algorithmic inventions and software systems that transcend disciplines and scales. Carried on a wave of digital technology, CSE brings the power of parallelism to bear on troves of data. Mathematics-based advanced computing has become a prevalent means of discovery and innovation in essentially all areas of science, engineering, technology, and society; and the CSE community is at the core of this transformation. However, a combination of disruptive developments---including the architectural complexity of extreme-scale computing, the data revolution that engulfs the planet, and the specialization required to follow the applications to new frontiers---is redefining the scope and reach of the CSE endeavor. This report describes the rapid expansion of CSE and the challenges to sustaining its bold advances. The report also presents strategies and directions for CSE research and education for the next decade.Comment: Major revision, to appear in SIAM Revie

    Traditional and Health-Related Philanthropy: The Role of Resources and Personality

    Get PDF
    I study the relationships of resources and personality characteristics to charitable giving, postmortem organ donation, and blood donation in a nationwide sample of persons in households in the Netherlands. I find that specific personality characteristics are related to specific types of giving: agreeableness to blood donation, empathic concern to charitable giving, and prosocial value orientation to postmortem organ donation. I find that giving has a consistently stronger relation to human and social capital than to personality. Human capital increases giving; social capital increases giving only when it is approved by others. Effects of prosocial personality characteristics decline at higher levels of these characteristics. Effects of empathic concern, helpfulness, and social value orientations on generosity are mediated by verbal proficiency and church attendance.

    Norovirus Transmission on Cruise Ship

    Get PDF
    We documented transmission by food and person-to-person contact; persistence of virus despite sanitization onboard, including introductions of new strains; and seeding of an outbreak on land
    • …
    corecore