116 research outputs found

    Responsivity-based Criterion For Accurate Calibration Of Ftir Emission Spectra: Theoretical Development And Bandwidth Estimation

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    An analytical expression for the variance of the radiance measured by Fourier-transform infrared (FTIR) emission spectrometers exists only in the limit of low noise. Outside this limit, the variance needs to be calculated numerically. In addition, a criterion for low noise is needed to identify properly calibrated radiances and optimize the instrument bandwidth. In this work, the variance and the magnitude of a noise-dependent spectral bias are calculated as a function of the system responsivity (r) and the noise level in its estimate (sigma(r)). The criterion sigma(r)/r \u3c 0.3, applied to downwelling and upwelling FTIR emission spectra, shows that the instrument bandwidth is specified properly for one instrument but needs to be restricted for another

    A responsitivity-based criterion for accurate calibration of FTIR spectra: theoretical development and bandwidth estimation

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    An analytical expression for the variance of the radiance measured by Fourier-transform infrared (FTIR) emission spectrometers exists only in the limit of low noise. Outside this limit, the variance needs to be calculated numerically. In addition, a criterion for low noise is needed to identify properly calibrated radiances and optimize the instrument bandwidth. In this work, the variance and the magnitude of a noise-dependent spectral bias are calculated as a function of the system responsivity (r) and the noise level in its estimate (? r ). The criterion ? r /

    Evaluation of Temperature-Dependent Complex Refractive Indices of Supercooled Liquid Water Using Downwelling Radiance and In-Situ Cloud Measurements at South Pole

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    Clouds have a large effect on the radiation budget and represent a major source of uncertainty in climate models. Supercooled liquid clouds can exist at temperatures as low as 235 K, and the radiative effect of these clouds depends on the complex refractive index (CRI) of liquid water. Laboratory measurements have demonstrated that the liquid-water CRI is temperature-dependent, but corroboration with field measurements is difficult. Here we present measurements of the downwelling infrared radiance and in-situ measurements of supercooled liquid water in a cloud at temperatures as low as 240 K, made at South Pole Station in 2001. These results demonstrate that including the temperature dependence of the liquid-water CRI is essential for accurate calculations of radiative transfer through supercooled liquid clouds. Furthermore, we show that when cloud properties are retrieved from infrared radiances (using the spectral range 500–1,200 cm−1) spurious ice may be retrieved if the 300 K CRI is used for cold liquid clouds (∼240 K). These results have implications for radiative transfer in climate models as well as for retrievals of cloud properties from infrared radiance spectra.publishedVersio

    Evaluation of Six Atmospheric Reanalyses over Arctic Sea Ice from Winter to Early Summer

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    © Copyright 19 June 2019 American Meteorological Society (AMS). Permission to use figures, tables, and brief excerpts from this work in scientific and educational works is hereby granted provided that the source is acknowledged. Any use of material in this work that is determined to be “fair use” under Section 107 of the U.S. Copyright Act or that satisfies the conditions specified in Section 108 of the U.S. Copyright Act (17 USC §108) does not require the AMS’s permission. Republication, systematic reproduction, posting in electronic form, such as on a website or in a searchable database, or other uses of this material, except as exempted by the above statement, requires written permission or a license from the AMS. All AMS journals and monograph publications are registered with the Copyright Clearance Center (http://www.copyright.com). Questions about permission to use materials for which AMS holds the copyright can also be directed to [email protected]. Additional details are provided in the AMS Copyright Policy statement, available on the AMS website (http://www.ametsoc.org/CopyrightInformation).This study evaluates the performance of six atmospheric reanalyses (ERA-Interim, ERA5, JRA-55, CFSv2, MERRA-2, and ASRv2) over Arctic sea ice from winter to early summer. The reanalyses are evaluated using observations from the Norwegian Young Sea Ice campaign (N-ICE2015), a 5-month ice drift in pack ice north of Svalbard. N-ICE2015 observations include surface meteorology, vertical profiles from radiosondes, as well as radiative and turbulent heat fluxes. The reanalyses simulate surface analysis variables well throughout the campaign, but have difficulties with most forecast variables. Wintertime (January–March) correlation coefficients between the reanalyses and observations are above 0.90 for the surface pressure, 2-m temperature, total column water vapor, and downward longwave flux. However, all reanalyses have a positive wintertime 2-m temperature bias, ranging from 1° to 4°C, and negative (i.e., upward) net longwave bias of 3–19 W m−2. These biases are associated with poorly represented surface inversions and are largest during cold-stable periods. Notably, the recent ERA5 and ASRv2 datasets have some of the largest temperature and net longwave biases, respectively. During spring (April–May), reanalyses fail to simulate observed persistent cloud layers. Therefore they overestimate the net shortwave flux (5–79 W m−2) and underestimate the net longwave flux (8–38 W m−2). Promisingly, ERA5 provides the best estimates of downward radiative fluxes in spring and summer, suggesting improved forecasting of Arctic cloud cover. All reanalyses exhibit large negative (upward) residual heat flux biases during winter, and positive (downward) biases during summer. Turbulent heat fluxes over sea ice are simulated poorly in all seasons

    Multi-transcriptome analysis following an acute skeletal muscle growth stimulus yields tools for discerning global and MYC regulatory networks

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    Myc is a powerful transcription factor implicated in epigenetic reprogramming, cellular plasticity, and rapid growth as well as tumorigenesis. Cancer in skeletal muscle is extremely rare despite marked and sustained Myc induction during loading-induced hypertrophy. Here, we investigated global, actively transcribed, stable, and myonucleus-specific transcriptomes following an acute hypertrophic stimulus in mouse plantaris. With these datasets, we define global and Myc-specific dynamics at the onset of mechanical overload-induced muscle fiber growth. Data collation across analyses reveals an under-appreciated role for the muscle fiber in extracellular matrix remodeling during adaptation, along with the contribution of mRNA stability to epigenetic-related transcript levels in muscle. We also identify Runx1 and Ankrd1 (Marp1) as abundant myonucleus-enriched loading-induced genes. We observed that a strong induction of cell cycle regulators including Myc occurs with mechanical overload in myonuclei. Additionally, in vivo Myc-controlled gene expression in the plantaris was defined using a genetic muscle fiber-specific doxycycline-inducible Myc-overexpression model. We determined Myc is implicated in numerous aspects of gene expression during early-phase muscle fiber growth. Specifically, brief induction of Myc protein in muscle represses Reverbα, Reverbβ, and Myh2 while increasing Rpl3, recapitulating gene expression in myonuclei during acute overload. Experimental, comparative, and in silico analyses place Myc at the center of a stable and actively transcribed, loading-responsive, muscle fiber–localized regulatory hub. Collectively, our experiments are a roadmap for understanding global and Myc-mediated transcriptional networks that regulate rapid remodeling in postmitotic cells. We provide open webtools for exploring the five RNA-seq datasets as a resource to the field

    Semiallogenic fusions of MSI+ tumor cells and activated B cells induce MSI-specific T cell responses

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    <p>Abstract</p> <p>Background</p> <p>Various strategies have been developed to transfer tumor-specific antigens into antigen presenting cells in order to induce cytotoxic T cell responses against tumor cells. One approach uses cellular vaccines based on fusions of autologous antigen presenting cells and allogeneic tumor cells. The fusion cells combine antigenicity of the tumor cell with optimal immunostimulatory capacity of the antigen presenting cells.</p> <p>Microsatellite instability caused by mutational inactivation of DNA mismatch repair genes results in translational frameshifts when affecting coding regions. It has been shown by us and others that these mutant proteins lead to the presentation of immunogenic frameshift peptides that are - in principle - recognized by a multiplicity of effector T cells.</p> <p>Methods</p> <p>We chose microsatellite instability-induced frameshift antigens as ideal to test for induction of tumor specific T cell responses by semiallogenic fusions of microsatellite instable carcinoma cells with CD40-activated B cells. Two fusion clones of HCT116 with activated B cells were selected for stimulation of T cells autologous to the B cell fusion partner. Outgrowing T cells were phenotyped and tested in functional assays.</p> <p>Results</p> <p>The fusion clones expressed frameshift antigens as well as high amounts of MHC and costimulatory molecules. Autologous T cells stimulated with these fusions were predominantly CD4<sup>+</sup>, activated, and reacted specifically against the fusion clones and also against the tumor cell fusion partner. Interestingly, a response toward 6 frameshift-derived peptides (of 14 tested) could be observed.</p> <p>Conclusion</p> <p>Cellular fusions of MSI<sup>+ </sup>carcinoma cells and activated B cells combine the antigen-presenting capacity of the B cell with the antigenic repertoire of the carcinoma cell. They present frameshift-derived peptides and can induce specific and fully functional T cells recognizing not only fusion cells but also the carcinoma cells. These hybrid cells may have great potential for cellular immunotherapy and this approach should be further analyzed in preclinical as well as clinical trials. Moreover, this is the first report on the induction of frameshift-specific T cell responses without the use of synthetic peptides.</p

    The utilisation of health research in policy-making: Concepts, examples and methods of assessment

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    The importance of health research utilisation in policy-making, and of understanding the mechanisms involved, is increasingly recognised. Recent reports calling for more resources to improve health in developing countries, and global pressures for accountability, draw greater attention to research-informed policy-making. Key utilisation issues have been described for at least twenty years, but the growing focus on health research systems creates additional dimensions. The utilisation of health research in policy-making should contribute to policies that may eventually lead to desired outcomes, including health gains. In this article, exploration of these issues is combined with a review of various forms of policy-making. When this is linked to analysis of different types of health research, it assists in building a comprehensive account of the diverse meanings of research utilisation. Previous studies report methods and conceptual frameworks that have been applied, if with varying degrees of success, to record utilisation in policy-making. These studies reveal various examples of research impact within a general picture of underutilisation. Factors potentially enhancing utilisation can be identified by exploration of: priority setting; activities of the health research system at the interface between research and policy-making; and the role of the recipients, or 'receptors', of health research. An interfaces and receptors model provides a framework for analysis. Recommendations about possible methods for assessing health research utilisation follow identification of the purposes of such assessments. Our conclusion is that research utilisation can be better understood, and enhanced, by developing assessment methods informed by conceptual analysis and review of previous studies

    Molecular networks of human muscle adaptation to exercise and age

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    Physical activity and molecular ageing presumably interact to precipitate musculoskeletal decline in humans with age. Herein, we have delineated molecular networks for these two major components of sarcopenic risk using multiple independent clinical cohorts. We generated genome-wide transcript profiles from individuals (n = 44) who then undertook 20 weeks of supervised resistance-exercise training (RET). Expectedly, our subjects exhibited a marked range of hypertrophic responses (3% to +28%), and when applying Ingenuity Pathway Analysis (IPA) up-stream analysis to ~580 genes that co-varied with gain in lean mass, we identified rapamycin (mTOR) signaling associating with growth (P = 1.4×10−30). Paradoxically, those displaying most hypertrophy exhibited an inhibited mTOR activation signature, including the striking down-regulation of 70 rRNAs. Differential analysis found networks mimicking developmental processes (activated all-trans-retinoic acid (ATRA, Z-score = 4.5; P = 6×10−13) and inhibited aryl-hydrocarbon receptor signaling (AhR, Z-score = −2.3; P = 3×10−7)) with RET. Intriguingly, as ATRA and AhR gene-sets were also a feature of endurance exercise training (EET), they appear to represent “generic” physical activity responsive gene-networks. For age, we found that differential gene-expression methods do not produce consistent molecular differences between young versus old individuals. Instead, utilizing two independent cohorts (n = 45 and n = 52), with a continuum of subject ages (18–78 y), the first reproducible set of age-related transcripts in human muscle was identified. This analysis identified ~500 genes highly enriched in post-transcriptional processes (P = 1×10−6) and with negligible links to the aforementioned generic exercise regulated gene-sets and some overlap with ribosomal genes. The RNA signatures from multiple compounds all targeting serotonin, DNA topoisomerase antagonism, and RXR activation were significantly related to the muscle age-related genes. Finally, a number of specific chromosomal loci, including 1q12 and 13q21, contributed by more than chance to the age-related gene list (P = 0.01–0.005), implying possible epigenetic events. We conclude that human muscle age-related molecular processes appear distinct from the processes regulated by those of physical activity
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