The 727 airplane side inlet low-speed performance confirmation model test for refanned JT8D engines

The results of a low-speed wind tunnel test of a 0.3 scale model 727 airplane side inlet for JT8D-100 engines are presented. The objectives of the test were to develop lines for a full-scale flightworthy inlet, to evaluate inlet total pressure recovery and steady-state total pressure distortion, and to obtain model-scale distortion data which can be used in the assessment of the compatibility of the inlet with the JT8D-100 series engines. A secondary objective was to obtain internal/external cowl static pressures for the determination of nacelle loads. Two basic inlet models were tested at static, forward speed, angle-of-attack (inflow angle), and cross-wind conditions. One model was with and one without an acoustic ring. Two modifications to the models were also tested, one with the ring closer to the inlet throat and one with a larger lip. Test measurements consisted of inlet surface static pressure, engine face total pressure, inlet airflow, tunnel total pressure, tunnel total temperature and tunnel velocity. Total pressure traverses were taken directly behind the ring and strut. No dynamic measurements were taken

Evaluation of the Relationship Between Stress Response and the Fecal Shedding of Escherichia Coli O157:H7

This study was conducted to determine if a relationship exists between temperament, stress response, and the shedding of Escerhichia coli O157:H7. Cattle (n = 150) were evaluated for disposition and stress response before shipping to the feeding operation, upon arrival at the feedlot, at approximately 70d on feed, and prior to transport to the harvesting facility. Chute and pen scores, as well as serum cortisol concentrations, were measured in order to assess individual temperament and stress response. A temperament index was created to classify cattle as Excitable, Intermediate, or Calm. The presence of E. coli O157:H7 was determined by rectal swabs on the live cattle and swabs of colons collected postmortem at the processing facility. As expected, variables for pre-shipment temperament index, exit velocity, pen score, arrival and midpoint exit velocity, and mid-point cortisol concentrations differed (P < 0.05) greatly between temperament groups. However, pre-shipment chute scores and cortisol concentration, as well as arrival and final cortisol concentrations differed (P < 0.05) only for Excitable cattle compared to both Calm and Intermediate groups. The percentage of cattle shedding the pathogen at arrival was approximately equal between temperament groups. When sampled before shipment to the processing facility, a higher proportion (P = 0.03) of cattle displaying Calm temperaments shed E. coli O157:H7 than the other groups. Results from postmortem colon samples exhibited a similar trend. When the results from all four sampling periods were pooled, the Calm cattle had a greater numerical percentage test positive for E. coli O157:H7. However, the pooled frequency distribution is largely dictated by the results of the final sampling time. Based on these results, it appears that Excitable cattle are not more likely to shed E. coli O157:H7. In fact, it seems that Calm cattle may be equally or more susceptible to shed at later points in the feeding period. However, it is important to note that a relatively small number of the samples tested positive for E. coli O157:H7, thus, potentially causing dramatic changes in the distributions

Evidence of external reconnection between an erupting mini-filament and ambient loops observed by Solar Orbiter/EUI

Mini-filament eruptions are one of the most common small-scale transients in the solar atmosphere. However, their eruption mechanisms are still not understood thoroughly. Here, with a combination of 174 A images of high spatio-temporal resolution taken by the Extreme Ultraviolet Imager on board Solar Orbiter and images of the Atmospheric Imaging Assembly on board Solar Dynamics Observatory, we investigate in detail an erupting mini-filament over a weak magnetic field region on 2022 March 4. Two bright ribbons clearly appeared underneath the erupting mini-filament as it quickly ascended, and subsequently, some dark materials blew out when the erupting mini-filament interacted with the outer ambient loops, thus forming a blowout jet characterized by a widening spire. At the same time, multiple small bright blobs of 1-2 Mm appeared at the interaction region and propagated along the post-eruption loops toward the footpoints of the erupting fluxes at a speed of ~ 100 km/s. They also caused a semi-circular brightening structure. Based on these features, we suggest that the mini-filament eruption first experiences internal and then external reconnection, the latter of which mainly transfers mass and magnetic flux of the erupting mini-filament to the ambient corona.Comment: 8 pages, 6 figures, accepted for publication in Astronomy & Astrophysic

Hypoxia-inducible factor 1 alpha-mediated RelB/APOBEC3B down-regulation allows hepatitis B virus persistence

Background and Aims: Therapeutic strategies against HBV focus, among others, on the activation of the immune system to enable the infected host to eliminate HBV. Hypoxia‐inducible factor 1 alpha (HIF1α) stabilization has been associated with impaired immune responses. HBV pathogenesis triggers chronic hepatitis‐related scaring, leading inter alia to modulation of liver oxygenation and transient immune activation, both factors playing a role in HIF1α stabilization. Approach and Results: We addressed whether HIF1α interferes with immune‐mediated induction of the cytidine deaminase, apolipoprotein B mRNA editing enzyme catalytic subunit 3B (APOBEC3B; A3B), and subsequent covalently closed circular DNA (cccDNA) decay. Liver biopsies of chronic HBV (CHB) patients were analyzed by immunohistochemistry and in situ hybridization. The effect of HIF1α induction/stabilization on differentiated HepaRG or mice ± HBV ± LTβR‐agonist (BS1) was assessed in vitro and in vivo. Induction of A3B and subsequent effects were analyzed by RT‐qPCR, immunoblotting, chromatin immunoprecipitation, immunocytochemistry, and mass spectrometry. Analyzing CHB highlighted that areas with high HIF1α levels and low A3B expression correlated with high HBcAg, potentially representing a reservoir for HBV survival in immune‐active patients. In vitro, HIF1α stabilization strongly impaired A3B expression and anti‐HBV effect. Interestingly, HIF1α knockdown was sufficient to rescue the inhibition of A3B up‐regulation and ‐mediated antiviral effects, whereas HIF2α knockdown had no effect. HIF1α stabilization decreased the level of v‐rel reticuloendotheliosis viral oncogene homolog B protein, but not its mRNA, which was confirmed in vivo. Noteworthy, this function of HIF1α was independent of its partner, aryl hydrocarbon receptor nuclear translocator. Conclusions: In conclusion, inhibiting HIF1α expression or stabilization represents an anti‐HBV strategy in the context of immune‐mediated A3B induction. High HIF1α, mediated by hypoxia or inflammation, offers a reservoir for HBV survival in vivo and should be considered as a restricting factor in the development of immune therapies

Observational Evidence of S-web Source of the Slow Solar Wind

From 2022 March 18 to 21, NOAA Active Region (AR) 12967 was tracked simultaneously by Solar Orbiter at 0.35 au and Hinode/EIS at Earth. During this period, strong blueshifted plasma upflows were observed along a thin, dark corridor of open magnetic field originating at the AR’s leading polarity and continuing toward the southern extension of the northern polar coronal hole. A potential field source surface model shows large lateral expansion of the open magnetic field along the corridor. Squashing factor Q-maps of the large-scale topology further confirm super-radial expansion in support of the S-web theory for the slow wind. The thin corridor of upflows is identified as the source region of a slow solar wind stream characterized by ∼300 km s−1 velocities, low proton temperatures of ∼5 eV, extremely high density >100 cm−3, and a short interval of moderate Alfvénicity accompanied by switchback events. When the connectivity changes from the corridor to the eastern side of the AR, the in situ plasma parameters of the slow solar wind indicate a distinctly different source region. These observations provide strong evidence that the narrow open-field corridors, forming part of the S-web, produce some extreme properties in their associated solar wind streams

The solar-C (EUVST) mission: The latest status

Solar-C (EUVST) is the next Japanese solar physics mission to be developed with significant contributions from US and European countries. The mission carries an EUV imaging spectrometer with slit-jaw imaging system called EUVST (EUV High-Throughput Spectroscopic Telescope) as the mission payload, to take a fundamental step towards answering how the plasma universe is created and evolves and how the Sun influences the Earth and other planets in our solar system. In April 2020, ISAS (Institute of Space and Astronautical Science) of JAXA (Japan Aerospace Exploration Agency) has made the final down-selection for this mission as the 4th in the series of competitively chosen M-class mission to be launched with an Epsilon launch vehicle in mid 2020s. NASA (National Aeronautics and Space Administration) has selected this mission concept for Phase A concept study in September 2019 and is in the process leading to final selection. For European countries, the team has (or is in the process of confirming) confirmed endorsement for hardware contributions to the EUVST from the national agencies. A recent update to the mission instrumentation is to add a UV spectral irradiance monitor capability for EUVST calibration and scientific purpose. This presentation provides the latest status of the mission with an overall description of the mission concept emphasizing on key roles of the mission in heliophysics research from mid 2020

Intestinal B cells license metabolic T-cell activation in NASH microbiota/antigen-independently and contribute to fibrosis by IgA-FcR signalling

BACKGROUND & AIMS: The progression of non-alcoholic steatohepatitis (NASH) to fibrosis and hepatocellular carcinoma (HCC) is aggravated by auto-aggressive T cells. The gut-liver axis contributes to NASH, but the mechanisms involved and the consequences for NASH-induced fibrosis and liver cancer remain unknown. We investigated the role of gastrointestinal B cells in the development of NASH, fibrosis and NASH-induced HCC. METHODS: C57BL/6J wild-type (WT), B cell-deficient and different immunoglobulin-deficient or transgenic mice were fed distinct NASH-inducing diets or standard chow for 6 or 12 months, whereafter NASH, fibrosis, and NASH-induced HCC were assessed and analysed. Specific pathogen-free/germ-free WT and μMT mice (containing B cells only in the gastrointestinal tract) were fed a choline-deficient high-fat diet, and treated with an anti-CD20 antibody, whereafter NASH and fibrosis were assessed. Tissue biopsy samples from patients with simple steatosis, NASH and cirrhosis were analysed to correlate the secretion of immunoglobulins to clinicopathological features. Flow cytometry, immunohistochemistry and single-cell RNA-sequencing analysis were performed in liver and gastrointestinal tissue to characterise immune cells in mice and humans. RESULTS: Activated intestinal B cells were increased in mouse and human NASH samples and licensed metabolic T-cell activation to induce NASH independently of antigen specificity and gut microbiota. Genetic or therapeutic depletion of systemic or gastrointestinal B cells prevented or reverted NASH and liver fibrosis. IgA secretion was necessary for fibrosis induction by activating CD11b+CCR2+F4/80+CD11c-FCGR1+ hepatic myeloid cells through an IgA-FcR signalling axis. Similarly, patients with NASH had increased numbers of activated intestinal B cells; additionally, we observed a positive correlation between IgA levels and activated FcRg+ hepatic myeloid cells, as well the extent of liver fibrosis. CONCLUSIONS: Intestinal B cells and the IgA-FcR signalling axis represent potential therapeutic targets for the treatment of NASH. IMPACT AND IMPLICATIONS: There is currently no effective treatment for non-alcoholic steatohepatitis (NASH), which is associated with a substantial healthcare burden and is a growing risk factor for hepatocellular carcinoma (HCC). We have previously shown that NASH is an auto-aggressive condition aggravated, amongst others, by T cells. Therefore, we hypothesized that B cells might have a role in disease induction and progression. Our present work highlights that B cells have a dual role in NASH pathogenesis, being implicated in the activation of auto-aggressive T cells and the development of fibrosis via activation of monocyte-derived macrophages by secreted immunoglobulins (e.g., IgA). Furthermore, we show that the absence of B cells prevented HCC development. B cell-intrinsic signalling pathways, secreted immunoglobulins, and interactions of B cells with other immune cells are potential targets for combinatorial NASH therapies against inflammation and fibrosis

Molecular characterization of hepatocellular carcinoma in patients with nonalcoholic steatohepatitis

Background and aims: Non-alcoholic steatohepatitis (NASH)-related hepatocellular carcinoma (HCC) is increasing globally, but its molecular features are not well defined. We aimed to identify unique molecular traits characterising NASH-HCC compared to other HCC aetiologies. Methods: We collected 80 NASH-HCC and 125 NASH samples from 5 institutions. Expression array (n = 53 NASH-HCC; n = 74 NASH) and whole exome sequencing (n = 52 NASH-HCC) data were compared to HCCs of other aetiologies (n = 184). Three NASH-HCC mouse models were analysed by RNA-seq/expression-array (n = 20). Activin A receptor type 2A (ACVR2A) was silenced in HCC cells and proliferation assessed by colorimetric and colony formation assays. Results: Mutational profiling of NASH-HCC tumours revealed TERT promoter (56%), CTNNB1 (28%), TP53 (18%) and ACVR2A (10%) as the most frequently mutated genes. ACVR2A mutation rates were higher in NASH-HCC than in other HCC aetiologies (10% vs. 3%, p <0.05). In vitro, ACVR2A silencing prompted a significant increase in cell proliferation in HCC cells. We identified a novel mutational signature (MutSig-NASH-HCC) significantly associated with NASH-HCC (16% vs. 2% in viral/alcohol-HCC, p = 0.03). Tumour mutational burden was higher in non-cirrhotic than in cirrhotic NASH-HCCs (1.45 vs. 0.94 mutations/megabase; p <0.0017). Compared to other aetiologies of HCC, NASH-HCCs were enriched in bile and fatty acid signalling, oxidative stress and inflammation, and presented a higher fraction of Wnt/TGF-β proliferation subclass tumours (42% vs. 26%, p = 0.01) and a lower prevalence of the CTNNB1 subclass. Compared to other aetiologies, NASH-HCC showed a significantly higher prevalence of an immunosuppressive cancer field. In 3 murine models of NASH-HCC, key features of human NASH-HCC were preserved. Conclusions: NASH-HCCs display unique molecular features including higher rates of ACVR2A mutations and the presence of a newly identified mutational signature. Lay summary: The prevalence of hepatocellular carcinoma (HCC) associated with non-alcoholic steatohepatitis (NASH) is increasing globally, but its molecular traits are not well characterised. In this study, we uncovered higher rates of ACVR2A mutations (10%) - a potential tumour suppressor - and the presence of a novel mutational signature that characterises NASH-related HCC