1,903 research outputs found

    Implications of lymphocyte anergy to glycolipids in multiple sclerosis (MS): iNKT cells may mediate the MS infectious trigger

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    Immunogenic lipids may play key roles in host defenses against infection and in generating autoimmune inflammation and organ-specific damage. In multiple sclerosis (MS) there are unequivocal autoimmune features and vulnerability to aggravation or induction by microbial or viral infection. We have found glycolipid-driven anergy of circulating lymphocytes in MS indicating that this immune response is affected in MS and the robust effects of iNKT activation with potent cellular and cytokine activities emphasizes its potential importance. Diverse glycolipids including the endogenous myelin acetylated-galactosylceramides (AcGalCer) can drive activation that could be critical to the inflammatory demyelination in the central nervous system and clinical consequences. The iNKT cells and their invariant or iTCR (Vα24Jα18Vβ11) constitute an innate defense−a discrete immune arm that is separate from peptide-driven acquired immune responses. This offers new possibilities for insight including a likelihood that the pattern recognition of exogenous microbial and myelin immunogens can overlap and cross-react especially in an inflammatory milieu

    GOES-R Algorithms: A Common Science and Engineering Design and Development Approach for Delivering Next Generation Environmental Data Products

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    GOES-R, the next generation of the National Oceanic and Atmospheric Administration’s (NOAA) Geostationary Operational Environmental Satellite (GOES) System, represents a new technological era in operational geostationary environmental satellite systems. GOES-R will provide advanced products that describe the state of the atmosphere, land, oceans, and solar/ space environments over the western hemisphere. The Harris GOES-R Ground Segment team will provide the software, based on government-supplied algorithms, and engineering infrastructures designed to produce and distribute these next-generation data products. The Harris GOES-R Team has adopted an integrated applied science and engineering approach that combines rigorous system engineering methods, with modern software design elements to facilitate the transition of algorithms for Level 1 and 2+ products to operational software. The Harris Team GOES-R GS algorithm framework, which includes a common data model interface, provides general design principles and standardized methods for developing general algorithm services, interfacing to external data, generating intermediate and L1b and L2 products and implementing common algorithm features such as metadata generation and error handling. This work presents the suite of GOES-R products, their properties and the process by which the related requirements are maintained during the complete design/development life-cycle. It also describes the algorithm architecture/engineering approach that will be used to deploy these algorithms, and provides a preliminary implementation road map for the development of the GOES-R GS software infrastructure, and a view into the integration of the framework and data model into the final design

    Means and method of detection in chemical separation procedures

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    A means and method for indirect detection of constituent components of a mixture separated in a chemical separation process. Fluorescing ions are distributed across the area in which separation of the mixture will occur to provide a generally uniform background fluorescence intensity. For example, the mixture is comprised of one or more charged analytes which displace fluorescing ions where its constituent components separate to. Fluorescing ions of the same charge as the charged analyte components cause a displacement. The displacement results in the location of the separated components having a reduced fluorescence intensity to the remainder of the background. Detection of the lower fluorescence intensity areas can be visually, by photographic means and methods, or by automated laser scanning

    Examining the patient and caregiver experience with diazepam nasal spray for seizure clusters: Results from an exit survey of a phase 3, open-label, repeat-dose safety study

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    BACKGROUND: Ideal rescue treatments for acute treatment of seizure clusters should be easy to administer, so it is important to assess user perceptions of these treatments. Diazepam nasal spray is designed to have a rapid, noninvasive, and socially acceptable route of administration. Patient and caregiver (including care partner) responses to surveys from a phase 3 safety study of diazepam nasal spray are reported. METHODS: The study enrolled patients aged 6-65 years with seizure clusters. Surveys distributed to patients and caregivers at study end, completion, or discontinuation collected data on comfort using diazepam nasal spray outside the home, timing of administration and return to their usual selves, and comfort of use compared with rectal diazepam. Safety was assessed. RESULTS: Of 175 patients enrolled at the October 31, 2019, interim cutoff, 158 received diazepam nasal spray. Sixty-seven (42.4%) patients and 84 (53.2%) caregivers responded to the surveys (including 35 matched pairs). Most patients (78.8%, 52/66) responded that they were very comfortable doing activities outside the home with diazepam nasal spray available; 59.4% of patients returned to their usual selves within an hour of administration. Twenty-seven (40.3%) of these patients reported self-administration, 48% doing so at the first sign of a seizure. Administration of diazepam nasal spray was rated extremely or very easy by 93.8% of caregivers. Safety profile was consistent with diazepam rectal gel; no patient discontinued owing to treatment-emergent adverse events. Nasal discomfort was typically mild and transient. Among patients who had used diazepam rectal gel, most were not at all comfortable using it outside the home (86.7%) or at home (64.5%) compared with diazepam nasal spray, whereas caregivers reported that diazepam rectal gel was not at all easy to use compared with diazepam nasal spray. CONCLUSIONS: This survey from the phase 3 safety study of diazepam nasal spray shows that patients and caregivers were satisfied with, and more comfortable using, diazepam nasal spray than rectal diazepam in public. NCT02721069

    Femtolensing and Picolensing by Axion Miniclusters

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    Non-linear effects in the evolution of the axion field in the early Universe may lead to the formation of gravitationally bound clumps of axions, known as ``miniclusters.'' Minicluster masses and radii should be in the range Mmc∼10−12M⊙M_{\rm mc}\sim10^{-12} M_\odot and Rmc∼1010R_{\rm mc} \sim 10^{10}cm, and in plausible early-Universe scenarios a significant fraction of the mass density of the Universe may be in the form of axion miniclusters. If such axion miniclusters exist, they would have the physical properties required to be detected by ``femtolensing.''Comment: 7 pages plus 2 figures (Fig.1 avalible upon request), LaTe

    Brain mapping in a patient with congenital blindness – A case for multimodal approaches

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    Recent advances in basic neuroscience research across a wide range of methodologies have contributed significantly to our understanding of human cortical electrophysiology and functional brain imaging. Translation of this research into clinical neurosurgery has opened doors for advanced mapping of functionality that previously was prohibitively difficult, if not impossible. Here we present the case of a unique individual with congenital blindness and medically refractory epilepsy who underwent neurosurgical treatment of her seizures. Pre-operative evaluation presented the challenge of accurately and robustly mapping the cerebral cortex for an individual with a high probability of significant cortical re-organization. Additionally, a blind individual has unique priorities in one's ability to read Braille by touch and sense the environment primarily by sound than the non-vision impaired person. For these reasons we employed additional measures to map sensory, motor, speech, language, and auditory perception by employing a number of cortical electrophysiologic mapping and functional magnetic resonance imaging methods. Our data show promising results in the application of these adjunctive methods in the pre-operative mapping of otherwise difficult to localize, and highly variable, functional cortical areas

    Spatial Variability in the Ratio of Interstellar Atomic Deuterium to Hydrogen. I. Observations toward delta Orionis by the Interstellar Medium Absorption Profile Spectrograph

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    Studies of the abundances of deuterium in different astrophysical sites are of fundamental importance to answering the question about how much deuterium was produced during big bang nucleosynthesis and what fraction of it was destroyed later. With this in mind, we used the Interstellar Medium Absorption Profile Spectrograph (IMAPS) on the ORFEUS-SPAS II mission to observe at a wavelength resolution of 4 km/s (FWHM) the L-delta and L-epsilon absorption features produced by interstellar atomic deuterium in the spectrum of delta Ori A. A chi-square analysis indicated that 0.96 < N(D I)< 1.45e15 cm^{-2} at a 90% level of confidence, and the gas is at a temperature of about 6000K. To obtain an accurate value of N(H I) needed for a determination of the atomic ratio of D to H, we measured the L-alpha absorption features in 57 spectra of delta Ori in the IUE archive. From our measurement of N(H I)= 1.56e20 cm^{-2}, we found that N(D I)/N(H I)= 7.4(+1.9,-1.3)e-6 (90% confidence). Our result for D/H contrasts with the more general finding along other lines of sight that D/H is approximately 1.5e-5. The underabundance of D toward delta Ori A is not accompanied by an overabundance of N or O relative to H, as one might expect if the gas were subjected to more stellar processing than usual.Comment: 37 pages, 6 figures. Submitted to the Astrophysical Journa

    Microbial rRNA sequencing analysis of evaporative cooler indoor environments located in the Great Basin Desert region of the United States

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    Recent studies conducted in the Great Basin Desert region of the United States have shown that skin test reactivity to fungal and dust mite allergens are increased in children with asthma or allergy living in homes with evaporative coolers (EC). The objective of this study was to determine if the increased humidity previously reported in EC homes leads to varying microbial populations compared to homes with air conditioners (AC). Children with physician-diagnosed allergic rhinitis living in EC or AC environments were recruited into the study. Air samples were collected from the child's bedroom for genomic DNA extraction and metagenomic analysis of bacteria and fungi using the Illumina MiSeq sequencing platform. The analysis of bacterial populations revealed no major differences between EC and AC sampling environments. The fungal populations observed in EC homes differed from AC homes. The most prevalent species discovered in AC environments belonged to the genera Cryptococcus (20%) and Aspergillus (20%). In contrast, the most common fungi identified in EC homes belonged to the order Pleosporales and included Alternaria alternata (32%) and Phoma spp. (22%). The variations in fungal populations provide preliminary evidence of the microbial burden children may be exposed to within EC environments in this region

    An 11-Year Global Gridded Aerosol Optical Thickness Reanalysis (v1.0) for Atmospheric and Climate Sciences

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    While stand alone satellite and model aerosol products see wide utilization, there is a significant need in numerous atmospheric and climate applications for a fused product on a regular grid. Aerosol data assimilation is an operational reality at numerous centers, and like meteorological reanalyses, aerosol reanalyses will see significant use in the near future. Here we present a standardized 2003–2013 global 1 × 1 ◦ and 6-hourly modal aerosol optical thickness (AOT) reanalysis product. This data set can be applied to basic and applied Earth system science studies of significant aerosol events, aerosol impacts on numerical weather prediction, and electro-optical propagation and sensor performance, among other uses. This paper describes the science of how to develop and score an aerosol reanalysis product. This reanalysis utilizes a modified Navy Aerosol Analysis and Prediction System (NAAPS) at its core and assimilates quality controlled retrievals of AOT from the Moderate Resolution Imaging Spectroradiometer (MODIS) on Terra and Aqua and the Multi-angle Imaging SpectroRadiometer (MISR) on Terra. The aerosol source functions, including dust and smoke, were regionally tuned to obtain the best match between the model fine- and coarse-mode AOTs and the Aerosol Robotic Network (AERONET) AOTs. Other model processes, including deposition, were tuned to minimize the AOT difference between the model and satellite AOT. Aerosol wet deposition in the tropics is driven with satellite-retrieved precipitation, rather than the model field. The final reanalyzed fine- and coarse-mode AOT at 550 nm is shown to have good agreement with AERONET observations, with global mean root mean square error around 0.1 for both fine- and coarse-mode AOTs. This paper includes a discussion of issues particular to aerosol reanalyses that make them distinct from standard meteorological reanalyses, considerations for extending such a reanalysis outside of the NASA A-Train era, and examples of how the aerosol reanalysis can be applied or fused with other model or remote sensing products. Finally, the reanalysis is evaluated in comparison with other available studies of aerosol trends, and the implications of this comparison are discussed
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