208 research outputs found

    Mechanisms of NKT cell-mediated DC licensing and cross-priming

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    The detection and destruction of virus-infected or tumor cells is the main task of CD8+ T cells. Their activation needs to be tightly regulated to avoid the misguided killing of healthy cells. To this end, activation of CD8+ T cells requires not only antigenic signals but also additional costimulatory signals provided by mature DCs. The process that renders DCs capable of cross-priming has been termed DC licensing and can be induced by antigen-specific interactions with CD4+ TH cells. As the frequencies of specific antigen-bearing DCs and the relevant antigen-specific naïve CD4+ and CD8+ T cells are low, the involvement of chemokines as regulators of cell-cell interactions seems likely. Indeed, CCR5 has been described to be upregulated on naïve CD8+ T cells, thereby attracting these cells to the site of DC–CD4+ TH cell interactions, where the CCR5 ligands CCL3 and CCL4 are produced. Recently it has been established that not only CD4+ TH cells but also NKT cells can provide help for DC maturation, but the exact mechanisms remain unclear. The present study characterizes NKT cell-mediated DC licensing and presents a new aspect of DC licensing by demonstrating that the presentation of glycolipid antigens by DCs to NKT cells resulted not only in DC maturation but also in the expression of the chemokine CCL17 by the antigen-presenting DC. Moreover, it establishes that the induction of this chemokine is a critical component of DC licensing and is crucial for the generation of efficient CD8+ T cell responses, as the lack of CCL17 or its receptor CCR4 strongly impaired cross-priming. Several possible mechanisms for impaired cross-priming were investigated. Published findings of others made an effect on DCs and NKT cells most likely, but this was not the case. Instead, CCL17 increased the efficiency of cross-priming by acting directly on CD8+ T cells. Several experimental approaches revealed that CD8+ T cells that had upregulated CCR4 in response to a yet unknown factor were attracted by CCL17 towards licensed DCs. Additionally, CCL17 increased the DC–CD8+ T cell contact duration, thus promoting efficient scanning of the DC surface and enhancing the chances of efficient cross-presentation. These results identify CCL17 – CCR4 as a second chemokine – chemokine receptor pair that regulates cross-priming. Furthermore, they uncovered a previously unrecognized role of CCL17 and CCR4 in cytotoxic T cell responses. Finally, these results demonstrated that the two chemokine mechanisms that regulate classical and NKT cell-mediated cross-priming act in a synergistic manner by further increasing the efficiency of CD8+ T cell responses. Understanding the molecular mechanism of this synergistic effect may help improving vaccination strategies

    From BDI and stit to bdi-stit logic

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    Since it is desirable to be able to talk about rational agents forming attitudes toward their concrete agency, we suggest an introduction of doxastic, volitional, and intentional modalities into the multi-agent logic of deliberatively seeing to it that, dstit logic. These modalities are borrowed from the well-known BDI (belief-desire-intention) logic. We change the semantics of the belief and desire operators from a relational one to a monotonic neighbourhood semantic in order to handle ascriptions of conflicting but not inconsistent beliefs and desires as being satisfiable. The proposed bdi-stit logic is defined with respect to branching time frames, and it is shown that this logic is a generalization of a bdi logic based on branching time possible worlds frames (but without temporal operators) and dstit logic. The new bdi-stit logic generalizes bdi and dstit logic in the sense that for any model of bdi or dstit logic, there is an equivalent bdi-stit model

    Retrieving Precipitable Water Vapor From Shipborne Multi‐GNSS Observations

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    ©2019. American Geophysical UnionPrecipitable water vapor (PWV) is an important parameter for climate research and a crucial factor to achieve high accuracy in satellite geodesy and satellite altimetry. Currently Global Navigation Satellite System (GNSS) PWV retrieval using static Precise Point Positioning is limited to ground stations. We demonstrated the PWV retrieval using kinematic Precise Point Positioning method with shipborne GNSS observations during a 20‐day experiment in 2016 in Fram Strait, the region of the Arctic Ocean between Greenland and Svalbard. The shipborne GNSS PWV shows an agreement of ~1.1 mm with numerical weather model data and radiosonde observations, and a root‐mean‐square of ~1.7 mm compared to Satellite with ARgos and ALtiKa PWV. An improvement of 10% is demonstrated with the multi‐GNSS compared to the Global Positioning System solution. The PWV retrieval was conducted under different sea state from calm water up to gale. Such shipborne GNSS PWV has the promising potential to improve numerical weather forecasts and satellite altimetry

    Chemokines: A New Dendritic Cell Signal for T Cell Activation

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    Dendritic cells (DCs) are the main inducers and regulators of cytotoxic T lymphocyte (CTL) responses against viruses and tumors. One checkpoint to avoid misguided CTL activation, which might damage healthy cells of the body, is the necessity for multiple activation signals, involving both antigenic as well as additional signals that reflect the presence of pathogens. DCs provide both signals when activated by ligands of pattern recognition receptors and “licensed” by helper lymphocytes. Recently, it has been established that such T cell licensing can be facilitated by CD4+ T helper cells (“classical licensing”) or by natural killer T cells (“alternative licensing”). Licensing regulates the DC/CTL cross-talk at multiple layers. Direct recruitment of CTLs through chemokines released by licensed DCs has recently emerged as a common theme and has a crucial impact on the efficiency of CTL responses. Here, we discuss recent advances in our understanding of DC licensing for cross-priming and implications for the temporal and spatial regulation underlying this process. Future vaccination strategies will benefit from a deeper insight into the mechanisms that govern CTL activation

    Long-term monitoring of landfast sea ice extent and thickness in Kongsfjorden, and related applications (FastIce)

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    Landfast sea ice covers the inner parts of Kongsfjorden, Svalbard, for a limited time in winter and spring months, being an important feature for the physical and biological fjord systems. Systematic fast-ice monitoring for Kongsfjorden, as a part of a long-term project at the Norwegian Polar Institute (NPI) was started in 2003, with some more sporadic observations from 1997 to 2002. It includes the ice extent mapping and in situ measurements of ice and snow thickness, and freeboard at several sites in the fjord. The permanent presence of NPI personnel in Ny-Ålesund Research Station enables regular in situ fast-ice thickness measurements as long as the fast ice is accessible. Further, daily visits to the observatory on the mountain Zeppelinfjellet close to Ny-Ålesund, allow regular ice extent observations (weather, visibility, and daylight permitting). Data collected within this standardized monitoring programme have contributed to a number of studies. Monitoring of the sea-ice conditions in Kongsfjorden can be used to demonstrate and investigate phenomena related to climate change in the Arctic

    On the Response of Polarimetric GNSS-Reflectometry to Sea Surface Roughness

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    Reflectometry of Global Navigation Satellite Systems (GNSS) signals from the ocean surface has provided a new source of observations to study the ocean-atmosphere interaction. We investigate the sensitivity and performance of GNSS-Reflectometry (GNSS-R) data to retrieve sea surface roughness (SSR) as an indicator of sea state. A data set of one-year observations in 2016 is acquired from a coastal GNSS-R experiment in Onsala, Sweden. The experiment exploits two sea-looking antennas with right- and left-hand circular polarizations (RHCP and LHCP). The interference of the direct and reflected signals captured by the antennas is used by a GNSS-R receiver to generate complex interferometric fringes. We process the interferometric observations to estimate the contributions of direct signals and reflections to the total power. The power estimates are inverted to the SSR using the state-of-the-art model. The roughness measurements from the RHCP and LHCP links are evaluated against match-up wind measurements obtained from the nearest meteorological station. The results report on successful roughness retrieval with overall correlations of 0.76 for both links. However, the roughness effect in LHCP observations is more pronounced. The influence of surrounding complex coastlines and the wind direction dependence are discussed. The analysis reveals that the winds blowing from land have minimal impact on the roughness due to limited fetch. A clear improvement of roughness estimates with an overall correlation of 0.82 is observed for combined polarimetric observations from the RHCP and LHCP links. The combined observations can also improve the sensitivity of GNSS-R measurements to the change of sea state

    Ionospheric Impact on GNSS Reflectometry in the Tropical Region: A Simulation Study with NEDM model

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    The ionosphere is a layer of Earth's upper atmosphere that is ionized by solar radiation. It plays a crucial role in the propagation of Global Navigation Satellite System (GNSS) signals, as these signals pass through the ionosphere on their way from the GNSS satellite to the receiver. The irregularities in the ionospheric electron density may have a significant impact on the GNSS signals, causing delays and phase and amplitude scintillations. GNSS reflectometry (GNSS-R) is a promising technique for atmospheric sounding. Multiple studies have been successfully conducted in the recent decade by using GNSS-R ground-based, airborne and spaceborne data e.g., to estimate ionospheric disturbances from the reflected signals. However, further investigations are needed to precisely characterize ionospheric effects for GNSS-R altimetric applications. This study presents simulation results of ionospheric delay for reflection events located in tropical regions. The first-order ionospheric effects are estimated along the ray paths by deriving the slant total electron content from the Neustrelitz Electron Density Model (NEDM). The geometry of the simulated events refers to reflectometry records of the SPIRE satellite constellation and the satellite navigation system GPS on 2021/03/01. Initial analysis has shown promising results. As solar activity increases (indicated by solar radio flux F10.7 index), an increase in the total ionospheric phase delay is evident. Between 0h and 8h local time, there is a delay of 2 to 10 meters. For the time interval from 8h to 16h, the delay is from 14 up to 22 meters, with the maximum at noon. In the sunset period from 16h to 24h, the ionospheric delay reduces from 9 to 3 meters, respectively. The height above Earth’s surface at which the highest amount of electron content is found along the ray path is ~290 km. This altitude corresponds to the F-region which has the highest concentration of free electrons. The analyzed events correspond to elevation angles from 5 to 30 degrees. The highest ionospheric delay is found at elevation angles between 10 and 20 degrees depending also on the local time

    GNSS-based water vapor estimation and validation during the MOSAiC expedition

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    Within the transpolar drifting expedition MOSAiC (Multidisciplinary drifting Observatory for the Study of Arctic Climate), the Global Navigation Satellite System (GNSS) was used among other techniques to monitor variations in atmospheric water vapor. Based on 15 months of continuously tracked GNSS data including GPS, GLONASS and Galileo, epoch-wise coordinates and hourly zenith total delays (ZTDs) were determined using a kinematic precise point positioning (PPP) approach. The derived ZTD values agree to 1.1 ± 0.2 mm (root mean square (rms) of the differences 10.2 mm) with the numerical weather data of ECMWF's latest reanalysis, ERA5, computed for the derived ship's locations. This level of agreement is also confirmed by comparing the on-board estimates with ZTDs derived for terrestrial GNSS stations in Bremerhaven and Ny-Ålesund and for the radio telescopes observing very long baseline interferometry in Ny-Ålesund. Preliminary estimates of integrated water vapor derived from frequently launched radiosondes are used to assess the GNSS-derived integrated water vapor estimates. The overall difference of 0.08 ± 0.04 kg m−2 (rms of the differences 1.47 kg m−2) demonstrates a good agreement between GNSS and radiosonde data. Finally, the water vapor variations associated with two warm-air intrusion events in April 2020 are assessed

    Characterizing Ionospheric Effects on GNSS Reflectometry at Grazing Angles from Space

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    Coherent observations in GNSS reflectometry are prominent in regions with smooth reflecting surfaces and at grazing elevation angles. However, within these lower elevation ranges, GNSS signals traverse a more extensive atmospheric path, and increased ionospheric effects (e.g., delay biases) are expected. These biases can be mitigated by employing dual-frequency receivers or models tailored for single-frequency receivers. In preparation for the single-frequency GNSS-R ESA “PRETTY” mission, this study aims to characterize ionospheric effects under variable parameter conditions: elevation angles in the grazing range (5° to 30°), latitude-dependent regions (north, tropic, south) and diurnal changes (day and nighttime). The investigation employs simulations using orbit data from Spire Global Inc.’s Lemur-2 CubeSat constellation at the solar minimum (F10.7 index at 75) in March 2021. Changes towards higher solar activity are accounted for with an additional scenario (F10.7 index at 180) in March 2023. The electron density associated with each reflection event is determined using the Neustrelitz Electron Density Model (NEDM2020) and the NeQuick 2 model. The results from periods of low solar activity reveal fluctuations of up to approximately 300 TECUs in slant total electron content, 19 m in relative ionospheric delay for the GPS L1 frequency, 2 Hz in Doppler shifts, and variations in the peak electron density height ranging from 215 to 330 km. Sea surface height uncertainty associated with ionospheric model-based corrections in group delay altimetric inversion can reach a standard deviation at the meter level
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