2,658 research outputs found

    Prevention of “Humanized” Diabetogenic CD8 T-Cell Responses in HLA-Transgenic NOD Mice by a Multipeptide Coupled-Cell Approach

    Get PDF
    OBJECTIVE: Type 1 diabetes can be inhibited in standard NOD mice by autoantigen-specific immunotherapy targeting pathogenic CD8+ T-cells. NOD.beta2m(null).HHD mice expressing human HLA-A2.1 but lacking murine major histocompatibility complex class I molecules develop diabetes characterized by CD8 T-cells recognizing certain autoantigenic peptides also targeted in human patients. These include peptides derived from the pancreatic beta-cell proteins insulin (INS1/2 A(2-10) and INS1 B(5-14)) and islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP(265-273) and IGRP(228-236)). Hence, NOD.beta2m(null).HHD mice represent a model system for developing potentially clinically translatable interventions for suppressing diabetogenic HLA-A2.1-restricted T-cell responses. RESEARCH DESIGN AND METHODS: Starting at 4-6 weeks of age, NOD.beta2m(null).HHD female mice were injected intravenously with syngeneic splenocytes to which various admixtures of the four above-mentioned peptides were bound by the cross-linking agent ethylene carbodiimide (ECDI). RESULTS: Treatment with such cells bearing the complete cocktail of INS and IGRP epitopes (designated INS/IGRP-SPs) significantly inhibited diabetes development in NOD.beta2m(null).HHD recipients compared with controls receiving splenocytes coupled with an irrelevant HLA-A2.1-restricted Flu16 peptide. Subsequent analyses found syngeneic splenocytes bearing the combination of the two ECDI-coupled IGRPs but not INS peptides (IGRP-SPs or INS-SPs) effectively inhibited diabetes development in NOD.beta2m(null).HHD mice. This result was supported by enzyme-linked immunospot (ELISPOT) analyses indicating combined INS/IGRP-SPs diminished HLA-A2.1-restricted IGRP but not INS autoreactive CD8+ T-cell responses in NOD.beta2m(null).HHD mice. CONCLUSIONS: These data support the potential of a cell therapy approach targeting HLA-A2.1-restricted IGRP autoreactive CD8 T-cells as a diabetes intervention approach in appropriate human patients

    Large‐scale hydro‐climatology of the terrestrial Arctic drainage system

    Get PDF
    The large‐scale hydro‐climatology of the terrestrial Arctic drainage system is examined, focusing on the period 1960 onward. Special attention is paid to the Ob, Yenisey, Lena, and Mackenzie watersheds, which provide the bulk of freshwater discharge to the Arctic Ocean. Station data are used to compile monthly gridded time series of gauge‐corrected precipitation (P). Gridded time series of precipitation minus evapotranspiration (P−ET) are calculated from the moisture flux convergence using NCEP reanalysis data. Estimates of ET are obtained as a residual. Runoff (R) is obtained from available discharge records. For long‐term water‐year means, P−ET for the Yenisey, Lena, and Mackenzie watersheds is 16–20% lower than the observed runoff. In the Ob watershed, the two values agree within 9%. Given the uncertainties in P−ET, we consider the atmospheric and surface water budgets to be reasonably closed. Compared to the other three basins, the mean runoff ratio (R/P) is lower in the Ob watershed, consistent with the high fraction of annual precipitation lost through ET. All basins exhibit summer maxima in P and minima in P−ET. Summer P−ET in the Ob watershed is negative due to high ET rates. For large domains in northern Eurasia, about 25% of July precipitation is associated with the recycling of water vapor evapotranspirated within each domain. This points to a significant effect of the land surface on the hydrologic regime. Variability in P and P−ET has generally clear associations with the regional atmospheric circulation. A strong link with the Urals trough is documented for the Ob. Relationships with indices of the Arctic Oscillation and other teleconnections are generally weak. Water‐year time series of runoff and P−ET are strongly correlated in the Lena watershed only, reflecting extensive permafrost. Cold‐season runoff has increased in the Yenisey and Lena watersheds. This is most pronounced in the Yenisey watershed, where runoff has also increased sharply in spring, decreased in summer, but has increased for the year as a whole. The mechanisms for these changes are not entirely clear. While they fundamentally relate to higher air temperatures, increased winter precipitation, and strong summer drying, we speculate links with changes in active layer thickness and thawing permafrost

    Sea ice drift in the Arctic since the 1950s

    Get PDF
    Author Posting. © American Geophysical Union, 2008. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Geophysical Research Letters 35 (2008): L19704, doi:10.1029/2008GL034791.Sea ice drift data (from Russian North Pole stations, various ice camps, and the International Arctic Buoy Program) and surface wind stress data from the NCAR/NCEP Reanalysis are analyzed to determine their long-term trends and causality. The study finds that both parameters (ice drift and wind stress) show gradual acceleration over last 50 years. Significant positive trends are present in both winter and summer data. The major cause of observed positive trends is increasing Arctic storm activity over the Transpolar Drift Stream caused by a shift of storm tracks toward higher latitudes. It is speculated, with some observational evidence, that the increased stirring of the ocean by winds could hasten the transition of the Arctic toward a weakly stratified ocean with a potential for deep convection and a new sink for atmospheric CO2.We are grateful for funding from the NASA Headquarters, NSF and IARC

    Summer Atmospheric Circulation Anomalies over the Arctic Ocean and Their Influences on September Sea Ice Extent: A Cautionary Tale

    Get PDF
    Numerous studies have addressed links between summer atmospheric circulation patterns and inter-annual variability and the downward trend in total September Arctic sea ice extent. In general, low extent is favored when the preceding summer is characterized by positive sea level pressure (SLP) anomalies over the central Arctic Ocean north of Alaska. High extent is favored when low pressure dominates. If such atmospheric patterns could be predicted several months out, these links provide an avenue for improved seasonal predictability of total September extent. We analyze de-trended September extent time series (1979-2015), atmospheric reanalysis fields, ice age and motion, and AIRS data, to show that while there is merit to this summer circulation framework, it has limitations. Large departures in total September extent relative to the trend line are preceded by a wide range of summer circulation patterns. While patterns for the four years with the largest positive departures in September extent have below average SLP over the central Arctic Ocean, they differ markedly in the magnitude and location of pressure and air temperature anomalies. Differences in circulation for the four years with the largest negative departures are equally prominent. Circulation anomalies preceding Septembers with ice extent close to the trend also have a wide range of patterns. In turn, years (such as 2013 and 2014) with almost identical total September extent, were preceded by very different summer circulation patterns. September ice conditions can also be strongly shaped by events as far back as the previous winter or spring

    Variability, trends and predictability of seasonal sea ice retreat and advance in the Chukchi Sea

    Get PDF
    As assessed over the period 1979–2014, the date that sea ice retreats to the shelf break (150 m contour) of the Chukchi Sea has a linear trend of −0.7 days per year. The date of seasonal ice advance back to the shelf break has a steeper trend of about +1.5 days per year, together yielding an increase in the open water period of 80 days. Based on detrended time series, we ask how interannual variability in advance and retreat dates relate to various forcing parameters including radiation fluxes, temperature and wind (from numerical reanalyses), and the oceanic heat inflow through the Bering Strait (from in situ moorings). Of all variables considered, the retreat date is most strongly correlated (r ∼ 0.8) with the April through June Bering Strait heat inflow. After testing a suite of statistical linear models using several potential predictors, the best model for predicting the date of retreat includes only the April through June Bering Strait heat inflow, which explains 68% of retreat date variance. The best model predicting the ice advance date includes the July through September inflow and the date of retreat, explaining 67% of advance date variance. We address these relationships by discussing heat balances within the Chukchi Sea, and the hypothesis of oceanic heat transport triggering ocean heat uptake and ice-albedo feedback. Developing an operational prediction scheme for seasonal retreat and advance would require timely acquisition of Bering Strait heat inflow data. Predictability will likely always be limited by the chaotic nature of atmospheric circulation patterns

    The large‐scale freshwater cycle of the Arctic

    Get PDF
    This paper synthesizes our understanding of the Arctic\u27s large‐scale freshwater cycle. It combines terrestrial and oceanic observations with insights gained from the ERA‐40 reanalysis and land surface and ice‐ocean models. Annual mean freshwater input to the Arctic Ocean is dominated by river discharge (38%), inflow through Bering Strait (30%), and net precipitation (24%). Total freshwater export from the Arctic Ocean to the North Atlantic is dominated by transports through the Canadian Arctic Archipelago (35%) and via Fram Strait as liquid (26%) and sea ice (25%). All terms are computed relative to a reference salinity of 34.8. Compared to earlier estimates, our budget features larger import of freshwater through Bering Strait and larger liquid phase export through Fram Strait. While there is no reason to expect a steady state, error analysis indicates that the difference between annual mean oceanic inflows and outflows (∼8% of the total inflow) is indistinguishable from zero. Freshwater in the Arctic Ocean has a mean residence time of about a decade. This is understood in that annual freshwater input, while large (∼8500 km3), is an order of magnitude smaller than oceanic freshwater storage of ∼84,000 km3. Freshwater in the atmosphere, as water vapor, has a residence time of about a week. Seasonality in Arctic Ocean freshwater storage is nevertheless highly uncertain, reflecting both sparse hydrographic data and insufficient information on sea ice volume. Uncertainties mask seasonal storage changes forced by freshwater fluxes. Of flux terms with sufficient data for analysis, Fram Strait ice outflow shows the largest interannual variability

    New climate models reveal faster and larger increases in Arctic precipitation than previously projected

    Get PDF
    As the Arctic continues to warm faster than the rest of the planet, evidence mounts that the region is experiencing unprecedented environmental change. The hydrological cycle is projected to intensify throughout the twenty-first century, with increased evaporation from expanding open water areas and more precipitation. The latest projections from the sixth phase of the Coupled Model Intercomparison Project (CMIP6) point to more rapid Arctic warming and sea-ice loss by the year 2100 than in previous projections, and consequently, larger and faster changes in the hydrological cycle. Arctic precipitation (rainfall) increases more rapidly in CMIP6 than in CMIP5 due to greater global warming and poleward moisture transport, greater Arctic amplification and sea-ice loss and increased sensitivity of precipitation to Arctic warming. The transition from a snow- to rain-dominated Arctic in the summer and autumn is projected to occur decades earlier and at a lower level of global warming, potentially under 1.5 °C, with profound climatic, ecosystem and socio-economic impacts

    Linkages between Arctic summer circulation regimes and regional sea ice anomalies

    Get PDF
    The downward trend in overall Arctic summer sea ice extent has been substantial, particularly in the last few decades. Departures in ice extent from year to year can be very large, however, in part due to the high variability in summer atmospheric circulation patterns. Anomalies in the Pacific sector ice cover can be partially compensated by anomalies of opposite sign in the Atlantic sector. An assessment of linkages between summer atmospheric patterns and sectoral anomalies in the area of maximum open water north of 70°N demonstrates that there is asymmetry in the mechanisms. Years with low ice extent and high open water fraction are uniformly associated with positive temperature anomalies and southerly flow in both the Atlantic and Pacific sectors. However, years with high extent and low open water fraction in both sectors reveal two dominant mechanisms. Some years with anomalously low maximum open water fraction are associated with negative temperature anomalies and southerly transport—a cool summer pattern that allows ice to persist over larger areas. However, other low open water years are characterized by an “ice factory” mechanism, whereby—even when melting—ice cover is continually replenished by advection from the north
    corecore