3,125 research outputs found

    Novel Humanized Recombinant T Cell Receptor Ligands Protect the Female Brain After Experimental Stroke

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    Transmigration of peripheral leukocytes to the brain is a major contributor to cerebral ischemic cell death mechanisms. Humanized partial major histocompatibility complex class II constructs (pMHC), covalently linked to myelin peptides, are effective for treating experimental stroke in males, but new evidence suggests that some inflammatory cell death mechanisms after brain injury are sex-specific. We here demonstrate that treatment with pMHC constructs also improves outcomes in female mice with middle cerebral artery occlusion (MCAO). HLA-DR2 transgenic female mice with MCAO were treated with RTL1000 (HLA-DR2 moiety linked to human MOG-35-55 peptide), HLA-DRa1-MOG-35-55, or vehicle (VEH) at 3, 24, 48, and 72 h after reperfusion and were recovered for 96 h or 2 weeks post-injury for measurement of histology (TTC staining) or behavioral testing. RTL1000- and DRa1-MOG-treated mice had profoundly reduced infarct volumes as compared to the VEH group, although higher doses of DRa1-MOG were needed for females vs. males evaluated previously. RTL1000-treated females also exhibited strongly improved functional recovery in a standard cylinder test. In novel studies of post-ischemic ultrasonic vocalization (USV), as measured by animal calls to their cage mates, we modeled in mice the post-stroke speech deficits common in human stroke survivors. The number of calls was reduced in injured animals relative to pre-MCAO baseline regardless of RTL1000 treatment status. However, call duration was significantly improved by RTL1000 treatment, suggesting benefit to the animal’s recovery of vocalization capability. We conclude that both the parent RTL1000 molecule and the novel non-polymorphic DRα1-MOG-35-55 construct were highly effective immunotherapies for treatment of transient cerebral ischemia in females

    understanding the consequences of changes in the production frontiers for roots tubers and bananas

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    Abstract The widely recognized role of roots, tubers and bananas (RT&Bs) in achieving food security and providing income opportunities in the world's poorest regions will be challenged by socioeconomic and climate related drivers. These will affect demand and production patterns and increase pressure on farming systems. Foresight results presented in this paper show that the importance of RT&B crops for food security will likely increase by 2050 despite these challenges. Furthermore, investments targeted at yield growth appear to be more effective than marketing improvements in alleviating production constraints and in strengthening the role of RT&B crops in future food systems

    Horizontal coherence of low-frequency fixed-path sound in a continental shelf region with internal-wave activity

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    Author Posting. © Acoustical Society of America, 2012. This article is posted here by permission of Acoustical Society of America for personal use, not for redistribution. The definitive version was published in Journal of the Acoustical Society of America 131 (2012): 1782-1797, doi:10.1121/1.3666003.Sound at 85 to 450 Hz propagating in approximately 80-m depth water from fixed sources to a joint horizontal/vertical line array (HLA/VLA) is analyzed. The data are from a continental shelf area east of Delaware Bay (USA) populated with tidally generated long- and short-wavelength internal waves. Sound paths are 19 km in the along-shore (along internal-wave crest) direction and 30 km in the cross-shore direction. Spatial statistics of HLA arrivals are computed as functions of beam steering angle and time. These include array gain, horizontally lagged spatial correlation function, and coherent beam power. These quantities vary widely in magnitude, and vary over a broad range of time scales. For example, correlation scale can change rapidly from forty to five wavelengths, and correlation-scale behavior is anisotropic. In addition, the vertical array can be used to predict correlation expected for adiabatic propagation with cylindrical symmetry, forming a benchmark. Observed variations are in concert with internal-wave activity. Temporal variations of three coherence measures, horizontal correlation length, array gain, and ratio of actual correlation length to predicted adiabatic-mode correlation length, are very strong, varying by almost a factor of ten as internal waves pass.This work was supported by Office of Naval Research (ONR) Grants Nos. N00014-05-1-0482 and N00014-11-1- 0194 to T.F.D., ONR Grant No. N00014-04-1-0146 to J.F.L., and an ONR Ocean Acoustics Postdoctoral Fellowship awarded to J.M.C. under Professor William Carey at Boston University

    Observations of sound-speed fluctuations on the New Jersey continental shelf in the summer of 2006

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    Author Posting. © Acoustical Society of America, 2012. This article is posted here by permission of Acoustical Society of America for personal use, not for redistribution. The definitive version was published in Journal of the Acoustical Society of America 131 (2012): 1733-1748, doi:10.1121/1.3666014.Environmental sensors moored on the New Jersey continental shelf tracked constant density surfaces (isopycnals) for 35 days in the summer of 2006. Sound-speed fluctuations from internal-wave vertical isopycnal displacements and from temperature/salinity variability along isopycnals (spiciness) are analyzed using frequency spectra and vertical covariance functions. Three varieties of internal waves are studied: Diffuse broadband internal waves (akin to waves fitting the deep water Garrett/Munk spectrum), internal tides, and, to a lesser extent, nonlinear internal waves. These internal-wave contributions are approximately distinct in the frequency domain. It is found that in the main thermocline spicy thermohaline structure dominates the root mean square sound-speed variability, with smaller contributions coming from (in order) nonlinear internal waves, diffuse internal waves, and internal tides. The frequency spectra of internal-wave displacements and of spiciness have similar form, likely due to the advection of variable-spiciness water masses by horizontal internal-wave currents, although there are technical limitations to the observations at high frequency. In the low-frequency, internal-wave band the internal-wave spectrum follows frequency to the −1.81 power, whereas the spice spectrum shows a −1.73 power. Mode spectra estimated via covariance methods show that the diffuse internal-wave spectrum has a smaller mode bandwidth than Garrett/Munk and that the internal tide has significant energy in modes one through three.This work was supported by the Office of Naval Research, and Professor Colosi gratefully acknowledges his additional support from the Naval Postgraduate School’s Undersea Warfare Chair that he holds
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