226 research outputs found

    Influence of the angular scattering of electrons on the runaway threshold in air

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    International audienceThe runaway electron mechanism is of great importance for the understanding of the generation of x- and gamma rays in atmospheric discharges. In 1991, terrestrial gamma-ray flashes (TGFs) were discovered by the Compton Gamma-Ray Observatory. Those emissions are bremsstrahlung from high energy electrons that run away in electric fields associated with thunderstorms. In this paper, we discuss the runaway threshold definition with a particular interest in the influence of the angular scattering for electron energy close to the threshold. In order to understand the mechanism of runaway, we compare the outcome of different FokkerPlanck and Monte Carlo models with increasing complexity in the description of the scattering. The results show that the inclusion of the stochastic nature of collisions smooths the probability to run away around the threshold. Furthermore, we observe that a significant number of electrons diffuse out of the runaway regime when we take into account the diffusion in angle due to the scattering. Those results suggest using a runaway threshold energy based on the FokkerPlanck model assuming the angular equilibrium that is 1.6 to 1.8 times higher than the one proposed by [1, 2], depending on the magnitude of the ambient electric field. The threshold also is found to be 5 to 26 times higher than the one assuming forward scattering. We give a fitted formula for the threshold field valid over a large range of electric fields. Furthermore, we have shown that the assumption of forward scattering is not valid below 1 MeV where the runaway threshold usually is defined. These results are important for the thermal runaway and the runaway electron avalanche discharge mechanisms suggested to participate in the TGF generation

    Cellular HIV-1 DNA Levels in Drug Sensitive Strains Are Equivalent to Those in Drug Resistant Strains in Newly-Diagnosed Patients in Europe

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    Background HIV-1 genotypic drug resistance is an important threat to the success of antiretroviral therapy and transmitted resistance has reached 9% prevalence in Europe. Studies have demonstrated that HIV-1 DNA load in peripheral blood mononuclear cells (PBMC) have a predictive value for disease progression, independently of CD4 counts and plasma viral load. Methodology/Principal Findings Molecular-beacon-based real-time PCR was used to measure HIV-1 second template switch (STS) DNA in PBMC in newly-diagnosed HIV-1 patients across Europe. These patients were representative for the HIV-1 epidemic in the participating countries and were carrying either drug-resistant or sensitive viral strains. The assay design was improved from a previous version to specifically detect M-group HIV-1 and human CCR5 alleles. The findings resulted in a median of 3.32 log10HIV-1copies/106PBMC and demonstrated for the first time no correlation between cellular HIV-1 DNA load and transmitted drug-resistance. A weak association between cellular HIV-1 DNA levels with plasma viral RNA load and CD4+T-cell counts was also reconfirmed. Co-receptor tropism for 91% of samples, whether or not they conferred resistance, was CCR5. A comparison of pol sequences derived from RNA and DNA, resulted in a high similarity between the two. Conclusions/Significance An improved molecular-beacon-based real-time PCR assay is reported for the measurement of HIV-1 DNA in PBMC and has investigated the association between cellular HIV-1 DNA levels and transmitted resistance to antiretroviral therapy in newly-diagnosed patients from across Europe. The findings show no correlation between these two parameters, suggesting that transmitted resistance does not impact disease progression in HIV-1 infected individuals. The CCR5 co-receptor tropism predominance implies that both resistant and non-resistant strains behave similarly in early infection. Furth

    The SARS-CoV-2 spike protein binds and modulates estrogen receptors

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    The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein binds angiotensin-converting enzyme 2 as its primary infection mechanism. Interactions between S and endogenous proteins occur after infection but are not well understood. We profiled binding of S against >9000 human proteins and found an interaction between S and human estrogen receptor alpha (ER alpha). Using bioinformatics, supercomputing, and experimental assays, we identified a highly conserved and functional nuclear receptor coregulator (NRC) LXD-like motif on the S2 sub-unit. In cultured cells, S DNA transfection increased ER alpha cytoplasmic accumulation, and S treatment induced ER-dependent biological effects. Non-invasive imaging in SARS-CoV-2-infected hamsters localized lung pathology with increased ER alpha lung levels. Postmortem lung experiments from infected hamsters and humans confirmed an increase in cytoplasmic ER alpha and its colocalization with S in alveolar macrophages. These findings describe the discovery of a S-ER alpha interaction, imply a role for S as an NRC, and advance knowledge of SARS-CoV-2 biology and coronavirus disease 2019 pathology

    Critical review on biofilm methods

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    Biofilms are widespread in nature and constitute an important strategy implemented by microorganisms to survive in sometimes harsh environmental conditions. They can be beneficial or have a negative impact particularly when formed in industrial settings or on medical devices. As such, research into the formation and elimination of biofilms is important for many disciplines. Several new methodologies have been recently developed for, or adapted to, biofilm studies that have contributed to deeper knowledge on biofilm physiology, structure and composition. In this review, traditional and cutting-edge methods to study biofilm biomass, viability, structure, composition and physiology are addressed. Moreover, as there is a lack of consensus among the diversity of techniques used to grow and study biofilms. This review intends to remedy this, by giving a critical perspective, highlighting the advantages and limitations of several methods. Accordingly, this review aims at helping scientists in finding the most appropriate and up-to-date methods to study their biofilms.The authors would like to acknowledge the support from the EU COST Action BacFoodNet FA1202

    JWST NIRCam + NIRSpec: Interstellar medium and stellar populations of young galaxies with rising star formation and evolving gas reservoirs

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    We present an interstellar medium and stellar population analysis of three spectroscopically confirmed z > 7 galaxies in the Early Release Observations JWST/NIRCam and JWST/NIRSpec data of the SMACS J0723.3-7327 cluster. We use the Bayesian spectral energy distribution-fitting code PROSPECTOR with a flexible star formation history (SFH), a variable dust attenuation law, and a self-consistent model of nebular emission (continuum and emission lines). Importantly, we self-consistently fit both the emission line fluxes from JWST/NIRSpec and the broad-band photometry from JWST/NIRCam, taking into account slit-loss effects. We find that these three z=7.6-8.5 galaxies (M-* approximate to 10(8) M-circle dot) are young with rising SFHs and mass-weighted ages of 3-4 Myr, though we find indications for underlying older stellar populations. The inferred gas-phase metallicities broadly agree with the direct metallicity estimates from the auroral lines. The galaxy with the lowest gas-phase metallicity (Z(gas) = 0.06 Z(circle dot)) has a steeply rising SFH, is very compact ( <0.2 kpc), and has a high star formation rate surface density (Sigma(SFR) approximate to 22 M-circle dot yr(-1) kpc(-2)), consistent with rapid gas accretion. The two other objects with higher gas-phase metallicities show more complex multicomponent morphologies on kpc scales, indicating that their recent increase in star formation rate is driven by mergers or internal, gravitational instabilities. We discuss effects of assuming different SFH priors or only fitting the photometric data. Our analysis highlights the strength and importance of combining JWST imaging and spectroscopy for fully assessing the nature of galaxies at the earliest epochs

    Discovery and properties of the earliest galaxies with confirmed distances

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    © 2023 Springer Nature Limited. This is the accepted manuscript version of an article which has been published in final form at 10.1038/s41550-023-01921-1Surveys with James Webb Space Telescope (JWST) have discovered candidate galaxies in the first 400 Myr of cosmic time. The properties of these distant galaxies provide initial conditions for understanding early galaxy formation and cosmic reionisation. Preliminary indications have suggested these candidate galaxies may be more massive and abundant than previously thought. However, without spectroscopic confirmation of their distances to constrain their intrinsic brightnesses, their inferred properties remain uncertain. Here we report on four galaxies located in the JWST Advanced Deep Extragalactic Survey (JADES) Near-Infrared Camera (NIRCam) imaging with photometric redshifts z1013z\sim10-13 subsequently confirmed by JADES JWST Near- Infrared Spectrograph (NIRSpec) observations. These galaxies include the first redshift z>12z>12 systems both discovered and spectroscopically confirmed by JWST. Using stellar population modelling, we find the galaxies typically contain a hundred million solar masses in stars, in stellar populations that are less than one hundred million years old. The moderate star formation rates and compact sizes suggest elevated star formation rate surface densities, a key indicator of their formation pathways. Taken together, these measurements show that the first galaxies contributing to cosmic reionisation formed rapidly and with intense internal radiation fields.Peer reviewe

    Patterns of transmitted HIV drug resistance in Europe vary by risk group

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    Background: In Europe, a continuous programme (SPREAD) has been in place for ten years to study transmission of drug resistant HIV. We analysed time trends of transmitted drug resistance mutations (TDRM) in relation to the risk behaviour reported. Methods: HIV-1 patients newly diagnosed in 27 countries from 2002 through 2007 were included. Inclusion was representative for risk group and geographical distribution in the participating countries in Europe. Trends over time were calculated by logistic regression. Results: From the 4317 patients included, the majority was men-having-sex-with-men -MSM (2084, 48%), followed by heterosexuals (1501, 35%) and injection drug users (IDU) (355, 8%). MSM were more often from Western Europe origin, infected with subtype B virus, and recently infected (<1 year) (p<0.001). The prevalence of TDRM was highest in MSM (prevalence of 11.1%), followed by heterosexuals (6.6%) and IDU (5.1%, p<0.001). TDRM was predominantly ascribed to nucleoside reverse transcriptase inhibitors (NRTI) with a prevalence of 6.6% in MSM, 3.3% in heterosexuals and 2.0% in IDU (p = 0.001). A significant increase in resistance to non- nucleoside reverse transcriptase inhibitors (NNRTIs) and a decrease in resistance to protease inhibitors was observed in MSM (p = 0.008 and p = 0.006, respectively), but not in heterosexual patients (p = 0.68 and p = 0.14, respectively). Conclusions: MSM showed to have significantly higher TDRM prevalence compared to heterosexuals and IDU. The increasing NNRTI resistance in MSM is likely to negatively influence the therapy response of first-line therapy, as most include NNRTI drugs

    Viremic HIV Infected Individuals with High CD4 T Cells and Functional Envelope Proteins Show Anti-gp41 Antibodies with Unique Specificity and Function

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    BACKGROUND: CD4 T-cell decay is variable among HIV-infected individuals. In exceptional cases, CD4 T-cell counts remain stable despite high plasma viremia. HIV envelope glycoprotein (Env) properties, namely tropism, fusion or the ability to induce the NK ligand NKp44L, or host factors that modulate Env cytopathic mechanisms may be modified in such situation. METHODS: We identified untreated HIV-infected individuals showing non-cytopathic replication (VL>10,000 copies/mL and CD4 T-cell decay<50 cells/µL/year, Viremic Non Progressors, VNP) or rapid progression (CD4 T-cells<350 cells/µL within three years post-infection, RP). We isolated full-length Env clones and analyzed their functions (tropism, fusion activity and capacity to induce NKp44L expression on CD4 cells). Anti-Env humoral responses were also analyzed. RESULTS: Env clones isolated from VNP or RP individuals showed no major phenotypic differences. The percentage of functional clones was similar in both groups. All clones tested were CCR5-tropic and showed comparable expression and fusogenic activity. Moreover, no differences were observed in their capacity to induce NKp44L expression on CD4 T cells from healthy donors through the 3S epitope of gp41. In contrast, anti- Env antibodies showed clear functional differences: plasma from VNPs had significantly higher capacity than RPs to block NKp44L induction by autologous viruses. Consistently, CD4 T-cells isolated from VNPs showed undetectable NKp44L expression and specific antibodies against a variable region flanking the highly conserved 3S epitope were identified in plasma samples from these patients. Conversely, despite continuous antigen stimulation, VNPs were unable to mount a broad neutralizing response against HIV. CONCLUSIONS: Env functions (fusion and induction of NKp44L) were similar in viremic patients with slow or rapid progression to AIDS. However, differences in humoral responses against gp41 epitopes nearby 3S sequence may contribute to the lack of CD4 T cell decay in VNPs by blocking the induction of NKp44L by gp41

    Increase in transmitted resistance to non-nucleoside reverse transcriptase inhibitors among newly diagnosed HIV-1 infections in Europe

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    Background: One out of ten newly diagnosed patients in Europe was infected with a virus carrying a drug resistant mutation. We analysed the patterns over time for transmitted drug resistance mutations (TDRM) using data from the European Spread program.Methods: Clinical, epidemiological and virological data from 4317 patients newly diagnosed with HIV-1 infection between 2002 and 2007 were analysed. Patients were enrolled using a pre-defined sampling strategy.Results: The overall prevalence of TDRM in this period was 8.9% (95% CI: 8.1-9.8). Interestingly, significant changes over time in TDRM caused by the different drug classes were found. Whereas nucleoside resistance mutations remained constant at 5%, a significant decline in protease inhibitors resistance mutations was observed, from 3.9% in 2002 to 1.6% in 2007 (p = 0.001). In contrast, resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs) doubled from 2.0% in 2002 to 4.1% in 2007 (p = 0.004) with 58% of viral strains carrying a K103N mutation. Phylogenetic analysis showed that these temporal changes could not be explained by large clusters of TDRM.Conclusion: During the years 2002 to 2007 transmitted resistance to NNRTI has doubled to 4% in Europe. The frequent use of NNRTI in first-line regimens and the clinical impact of NNRTI mutations warrants continued monitoring
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