Storm‐time configuration of the inner magnetosphere: Lyon‐Fedder‐Mobarry MHD code, Tsyganenko model, and GOES observations

[1] We compare global magnetohydrodynamic (MHD) simulation results with an empirical model and observations to understand the magnetic field configuration and plasma distribution in the inner magnetosphere, especially during geomagnetic storms. The physics-based Lyon-Fedder-Mobarry (LFM) code simulates Earth\u27s magnetospheric topology and dynamics by solving the equations of ideal MHD. Quantitative comparisons of simulated events with observations reveal strengths and possible limitations and suggest ways to improve the LFM code. Here we present a case study that compares the LFM code to both a semiempirical magnetic field model and to geosynchronous measurements from GOES satellites. During a magnetic cloud event, the simulation and model predictions compare well qualitatively with observations, except during storm main phase. Quantitative statistical studies of the MHD simulation shows that MHD field lines are consistently under-stretched, especially during storm time (Dst \u3c −20 nT) on the nightside, a likely consequence of an insufficient representation of the inner magnetosphere current systems in ideal MHD. We discuss two approaches for improving the LFM result: increasing the simulation spatial resolution and coupling LFM with a ring current model based on drift physics (i.e., the Rice Convection Model (RCM)). We show that a higher spatial resolution LFM code better predicts geosynchronous magnetic fields (not only the average Bz component but also higher-frequency fluctuations driven by the solar wind). An early version of the LFM/RCM coupled code, which runs so far only for idealized events, yields a much-improved ring current, quantifiable by decreased field strengths at all local times compared to the LFM-only code

Effects of electrojet turbulence on a magnetosphere-ionosphere simulation of a geomagnetic storm

Ionospheric conductance plays an important role in regulating the response of the magnetosphere‐ionosphere system to solar wind driving. Typically, models of magnetosphere‐ionosphere coupling include changes to ionospheric conductance driven by extreme ultraviolet ionization and electron precipitation. This paper shows that effects driven by the Farley‐Buneman instability can also create significant enhancements in the ionospheric conductance, with substantial impacts on geospace. We have implemented a method of including electrojet turbulence (ET) effects into the ionospheric conductance model utilized within geospace simulations. Our particular implementation is tested with simulations of the Lyon‐Fedder‐Mobarry global magnetosphere model coupled with the Rice Convection Model of the inner magnetosphere. We examine the impact of including ET‐modified conductances in a case study of the geomagnetic storm of 17 March 2013. Simulations with ET show a 13% reduction in the cross polar cap potential at the beginning of the storm and up to 20% increases in the Pedersen and Hall conductance. These simulation results show better agreement with Defense Meteorological Satellite Program observations, including capturing features of subauroral polarization streams. The field‐aligned current (FAC) patterns show little differences during the peak of storm and agree well with Active Magnetosphere and Planetary Electrodynamics Response Experiment (AMPERE) reconstructions. Typically, the simulated FAC densities are stronger and at slightly higher latitudes than shown by AMPERE. The inner magnetospheric pressures derived from Tsyganenko‐Sitnov empirical magnetic field model show that the inclusion of the ET effects increases the peak pressure and brings the results into better agreement with the empirical model.This material is based upon work supported by NASA grants NNX14AI13G, NNX13AF92G, and NNX16AB80G. The National Center for Atmospheric Research is sponsored by the National Science Foundation. This work used the XSEDE and TACC computational facilities, supported by National Science Foundation grant ACI-1053575. We would like to acknowledge high-performance computing support from Yellowstone (ark:/85065/d7wd3xhc) provided by NCAR's Computational and Information Systems Laboratory, sponsored by the National Science Foundation. We thank the AMPERE team and the AMPERE Science Center for providing the Iridium derived data products. All model output, simulation codes, and analysis routines are being preserved on the NCAR High-Performance Storage System and will be made available upon written request to the lead author of this publication. (NNX14AI13G - NASA; NNX13AF92G - NASA; NNX16AB80G - NASA; National Science Foundation; ACI-1053575 - National Science Foundation

Helicobacter pylori Dampens HLA-II Expression on Macrophages via the Up-Regulation of miRNAs Targeting CIITA

Macrophages have a major role in infectious and inflammatory diseases, and the available data suggest that Helicobacter pylori persistence can be explained in part by the failure of the bacterium to be killed by professional phagocytes. Macrophages are cells ready to kill the engulfed pathogen, through oxygen-dependent and -independent mechanisms; however, their killing potential can be further augmented by the intervention of T helper (Th) cells upon the specific recognition of human leukocyte antigen (HLA)-II\u2013peptide complexes on the surface of the phagocytic cells. As it pertains to H. pylori, the bacterium is engulfed by macrophages, but it interferes with the phagosome maturation process leading to phagosomes with an altered degradative capacity, and to megasomes, wherein H. pylori resists killing. We recently showed that macrophages infected with H. pylori strongly reduce the expression of HLA-II molecules on the plasma membrane and this compromises the bacterial antigen presentation to Th lymphocytes. In this work, we demonstrate that H. pylori hampers HLA-II expression in macrophages, activated or non-activated by IFN-\u3b3, by down-regulating the expression of the class II major histocompatibility complex transactivator (CIITA), the \u201cmaster control factor\u201d for the expression of HLA class II genes. We provided evidence that this effect relies on the up-regulation of let-7f-5p, let-7i-5p, miR-146b-5p, and -185-5p targeting CIITA. MiRNA expression analysis performed on biopsies from H. pylori-infected patients confirmed the up-regulation of let-7i-5p, miR-146b-5p, and -185-5p in gastritis, in pre-invasive lesions, and in gastric cancer. Taken together, our results suggest that specific miRNAs may be directly involved in the H. pylori infection persistence and may contribute to confer the risk of developing gastric neoplasia in infected patients

Systemic T Cells Immunosuppression of Glioma Stem Cell-Derived Exosomes Is Mediated by Monocytic Myeloid-Derived Suppressor Cells

A major contributing factor to glioma development and progression is its ability to evade the immune system. Nano-meter sized vesicles, exosomes, secreted by glioma-stem cells (GSC) can act as mediators of intercellular communication to promote tumor immune escape. Here, we investigated the immunomodulatory properties of GCS-derived exosomes on different peripheral immune cell populations. Healthy donor peripheral blood mononuclear cells (PBMCs) stimulated with anti-CD3, anti-CD28 and IL-2, were treated with GSC-derived exosomes. Phenotypic characterization, cell proliferation, Th1/Th2 cytokine secretion and intracellular cytokine production were analysed by distinguishing among effector T cells, regulatory T cells and monocytes. In unfractionated PBMCs, GSC-derived exosomes inhibited T cell activation (CD25 and CD69 expression), proliferation and Th1 cytokine production, and did not affect cell viability or regulatory T-cell suppression ability. Furthermore, exosomes were able to enhance proliferation of purified CD4+ T cells. In PBMCs culture, glioma-derived exosomes directly promoted IL-10 and arginase-1 production and downregulation of HLA-DR by unstimulated CD14+ monocytic cells, that displayed an immunophenotype resembling that of monocytic myeloid-derived suppressor cells (Mo-MDSCs). Importantly, the removal of CD14+ monocytic cell fraction from PBMCs restored T-cell proliferation. The same results were observed with exosomes purified from plasma of glioblastoma patients. Our results indicate that glioma-derived exosomes suppress T-cell immune response by acting on monocyte maturation rather than on direct interaction with T cells. Selective targeting of Mo-MDSC to treat glioma should be considered with regard to how immune cells allow the acquirement of effector functions and therefore counteracting tumor progression

The Role of Mesoscale Plasma Sheet Dynamics in Ring Current Formation

During geomagnetically active periods ions are transported from the magnetotail into the inner magnetosphere and accelerated to energies of tens to hundreds of keV. These energetic ions, of mixed composition with the most important species being H+ and O+, become the dominant source of plasma pressure in the inner magnetosphere. Ion transport and acceleration can occur at different spatial and temporal scales ranging from global quasi-steady convection to localized impulsive injection events and may depend on the ion gyroradius. In this study we ascertain the relative importance of mesoscale flow structures and the effects of ion non-adiabaticity on the produced ring current. For this we use: global magnetohydrodynamic (MHD) simulations to generate self-consistent electromagnetic fields under typical driving conditions which exhibit bursty bulk flows (BBFs); and injected test particles, initialized to match the plasma moments of the MHD simulation, and subsequently evolved according to the kinetic equations of motion. We show that the BBFs produced by our simulation reproduce thermodynamic and magnetic statistics from in situ measurements and are numerically robust. Mining the simulation data we create a data set, over a billion points, connecting particle transport to characteristics of the MHD flow. From this we show that mesoscale bubbles, localized depleted entropy regions, and particle gradient drifts are critical for ion transport. Finally we show, using identical particle ensembles with varying mass, that O+ non-adiabaticity creates qualitative differences in energization and spatial distribution while H+ non-adiabaticity has non-negligible implications for loss timescales

Glioma-associated stem cells: A novel class of tumor-supporting cells able to predict prognosis of human low-grade gliomas.

Background: Translational medicine aims at transferring advances in basic science research into new approaches for diagnosis and treatment of diseases. Low-grade gliomas (LGG) have a heterogeneous clinical behavior that can be only partially predicted employing current state-of-the-art markers, hindering the decision-making process. To deepen our comprehension on tumor heterogeneity, we dissected the mechanism of interaction between tumor cells and relevant components of the neoplastic environment, isolating, from LGG and high-grade gliomas (HGG), proliferating stem cell lines from both the glioma stroma and, where possible, the neoplasm. Methods and Findings: We isolated glioma-associated stem cells (GASC) from LGG (n=40) and HGG (n=73). GASC showed stem cell features, anchorage-independent growth, and supported the malignant properties of both A172 cells and human glioma-stem cells, mainly through the release of exosomes. Finally, starting from GASC obtained from HGG (n=13) and LGG (n=12) we defined a score, based on the expression of 9 GASC surface markers, whose prognostic value was assayed on 40 subsequent LGG-patients. At the multivariate Cox analysis, the GASC-based score was the only independent predictor of overall survival and malignant progression free-survival. Conclusions: The microenvironment of both LGG and HGG hosts non-tumorigenic multipotent stem cells that can increase in vitro the biological aggressiveness of glioma-initiating cells through the release of exosomes. The clinical importance of this finding is supported by the strong prognostic value associated with the characteristics of GASC. This patient-based approach can provide a groundbreaking method to predict prognosis and to exploit novel strategies that target the tumor stroma

Understanding storm‐time ring current development through data‐model comparisons of a moderate storm

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/94635/1/jgra18489.pd

The PROVENT-C19 registry: A study protocol for international multicenter SIAARTI registry on the use of prone positioning in mechanically ventilated patients with COVID-19 ARDS

Background The worldwide use of prone position (PP) for invasively ventilated patients with COVID-19 is progressively increasing from the first pandemic wave in everyday clinical practice. Among the suggested treatments for the management of ARDS patients, PP was recommended in the Surviving Sepsis Campaign COVID-19 guidelines as an adjuvant therapy for improving ventilation. In patients with severe classical ARDS, some authors reported that early application of prolonged PP sessions significantly decreases 28-day and 90-day mortality. Methods and analysis Since January 2021, the COVID19 Veneto ICU Network research group has developed and implemented nationally and internationally the "PROVENT-C19 Registry", endorsed by the Italian Society of Anesthesia Analgesia Resuscitation and Intensive Care. . .'(SIAARTI). The PROVENT-C19 Registry wishes to describe 1. The real clinical practice on the use of PP in COVID-19 patients during the pandemic at a National and International level; and 2. Potential baseline and clinical characteristics that identify subpopulations of invasively ventilated patients with COVID-19 that may improve daily from PP therapy. This web-based registry will provide relevant information on how the database research tools may improve our daily clinical practice. Conclusions This multicenter, prospective registry is the first to identify and characterize the role of PP on clinical outcome in COVID-19 patients. In recent years, data emerging from large registries have been increasingly used to provide real-world evidence on the effectiveness, quality, and safety of a clinical intervention. Indeed observation-based registries could be effective tools aimed at identifying specific clusters of patients within a large study population with widely heterogeneous clinical characteristics. Copyright