59 research outputs found

    High-contrast Ultrabroadband Frontend Source for High Intensity Few-Cycle Lasers

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    An ultrabroadband seed source for high-power, high-contrast OPCPA systems at 800 nm is presented. The source is based on post compression in a hollow-core fiber followed by crossed polarized waves (XPW) filtering and is capable of delivering 80Ό\muJ, 5fs, CEP-stable (0.3rad RMS) pulses with excellent spectral and temporal qualit

    Passive coherent combining of CEP-stable few-cycles pulses from a temporally divided hollow fiber compressor

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    International audienceWe demonstrate a simple and robust passive coherent combining technique for temporal compression of millijouleenergy laser pulses down to few-cycle duration in a gas-filled hollow fiber. High combining efficiency is achieved byusing carefully oriented calcite plates for temporal pulse division and recombination. Carrier-envelope phase (CEP)-stable, 6-fs, 800-nm pulses with more than 0.6 mJ energy are routinely generated. This method could aid in theenergy scaling of CEP-stable hollow-fiber compressor systems

    Omp25-dependent engagement of SLAMF1 by Brucella abortus in dendritic cells limits acute inflammation and favours bacterial persistence in vivo

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    The strategies by which intracellular pathogenic bacteria manipulate innate immunity to establish chronicity are poorly understood. Here, we show that Brucella abortus outer membrane protein Omp25 specifically binds the immune cell receptor SLAMF1 in vitro. The Omp25-dependent engagement of SLAMF1 by B. abortus limits NF-ÎșB translocation in dendritic cells (DCs) with no impact on Brucella intracellular trafficking and replication. This in turn decreases pro-inflammatory cytokine secretion and impairs DC activation. The Omp25-SLAMF1 axis also dampens the immune response without affecting bacterial replication in vivo during the acute phase of Brucella infection in a mouse model. In contrast, at the chronic stage of infection, the Omp25/SLAMF1 engagement is essential for Brucella persistence. Interaction of a specific bacterial protein with an immune cell receptor expressed on the DC surface at the acute stage of infection is thus a powerful mechanism to support microbe settling in its replicative niche and progression to chronicity.Fil: Degos, Clara. Inserm; Francia. Centre National de la Recherche Scientifique; FranciaFil: Hysenaj, Lisiena. Inserm; Francia. Centre National de la Recherche Scientifique; FranciaFil: Gonzalez Espinoza, Gabriela. Inserm; Francia. Centre National de la Recherche Scientifique; FranciaFil: Arce Gorvel, Vilma. Inserm; Francia. Centre National de la Recherche Scientifique; FranciaFil: Gagnaire, AurĂ©lie. Inserm; Francia. Centre National de la Recherche Scientifique; FranciaFil: Papadopoulos, Alexia. Inserm; Francia. Centre National de la Recherche Scientifique; FranciaFil: Pasquevich, Karina Alejandra. Universidad Nacional de San MartĂ­n. Instituto de Investigaciones BiotecnolĂłgicas. - Consejo Nacional de Investigaciones CientĂ­ficas y TĂ©cnicas. Oficina de CoordinaciĂłn Administrativa Parque Centenario. Instituto de Investigaciones BiotecnolĂłgicas; ArgentinaFil: MĂ©resse, StĂ©phane. Inserm; Francia. Centre National de la Recherche Scientifique; FranciaFil: Cassataro, Juliana. Universidad Nacional de San MartĂ­n. Instituto de Investigaciones BiotecnolĂłgicas. - Consejo Nacional de Investigaciones CientĂ­ficas y TĂ©cnicas. Oficina de CoordinaciĂłn Administrativa Parque Centenario. Instituto de Investigaciones BiotecnolĂłgicas; ArgentinaFil: MĂ©met, Sylvie. Inserm; Francia. Centre National de la Recherche Scientifique; FranciaFil: Gorvel, Jean Pierre. Inserm; Francia. Centre National de la Recherche Scientifique; Franci

    Energy-scalable temporal cleaning device for femtosecond laser pulsesbased on cross-polarized wave generation

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    International audienceWe report on a compact energy-scalable device for generating high-fidelity femtosecond laser pulses based on spatial filtering through a hollow-core fiber followed by a nonlinear crystal for crosspolarized wave (XPW) generation. This versatile device is suited for temporal pulse cleaning over a wide range of input energies (from 0.1 to >10 mJ) and is successfully qualified on different ultrafast laser systems. Full characterization of the XPW output is presented. In particular, we demonstrate the generation of 1.6 mJ energy pulses starting from 11 mJ input pulse energy. The temporal contrast of the pulses is enhanced by more than 4 orders of magnitude. In addition, pulse shortening from 40 fs down to 15 fs Fourier-transform limit yields an overall peak-power transmission of up to 50%. This device not only serves as an integrated pulse contrast filter inside an ultrafast laser amplifier but also as a simple back-end solution for temporal post-compression of amplified pulses

    Vaccine breakthrough hypoxemic COVID-19 pneumonia in patients with auto-Abs neutralizing type I IFNs

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    Life-threatening `breakthrough' cases of critical COVID-19 are attributed to poor or waning antibody response to the SARS- CoV-2 vaccine in individuals already at risk. Pre-existing autoantibodies (auto-Abs) neutralizing type I IFNs underlie at least 15% of critical COVID-19 pneumonia cases in unvaccinated individuals; however, their contribution to hypoxemic breakthrough cases in vaccinated people remains unknown. Here, we studied a cohort of 48 individuals ( age 20-86 years) who received 2 doses of an mRNA vaccine and developed a breakthrough infection with hypoxemic COVID-19 pneumonia 2 weeks to 4 months later. Antibody levels to the vaccine, neutralization of the virus, and auto- Abs to type I IFNs were measured in the plasma. Forty-two individuals had no known deficiency of B cell immunity and a normal antibody response to the vaccine. Among them, ten (24%) had auto-Abs neutralizing type I IFNs (aged 43-86 years). Eight of these ten patients had auto-Abs neutralizing both IFN-a2 and IFN-., while two neutralized IFN-omega only. No patient neutralized IFN-ss. Seven neutralized 10 ng/mL of type I IFNs, and three 100 pg/mL only. Seven patients neutralized SARS-CoV-2 D614G and the Delta variant (B.1.617.2) efficiently, while one patient neutralized Delta slightly less efficiently. Two of the three patients neutralizing only 100 pg/mL of type I IFNs neutralized both D61G and Delta less efficiently. Despite two mRNA vaccine inoculations and the presence of circulating antibodies capable of neutralizing SARS-CoV-2, auto-Abs neutralizing type I IFNs may underlie a significant proportion of hypoxemic COVID-19 pneumonia cases, highlighting the importance of this particularly vulnerable population

    Definition, aims, and implementation of GA2LEN/HAEi Angioedema Centers of Reference and Excellence

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    COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

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    Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≀ 18 years: 69, 48, 23; 85%), older adults (≄ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

    1-mJ, sub-5-fs carrier-envelope phase-locked pulses

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    International audienceWe report the routine generation of sub-5-fs laser pulses with 1-mJ energy and stable carrier-envelope phase at 1-kHz repetition rate, obtained by compressing the multi-mJ output from a phase-locked Ti:sapphire amplifier in a rare-gas-filled hollow fiber. The dual-stage amplifier features a hybrid transmission grating/chirped mirror compressor providing 2.2-mJ, 26-fs pulses at 1 kHz with standard phase deviation of 190 mrad rms. We demonstrate hour-long phase stability without feedback control of grating position or rigorous control of the laser environment, simply by using small pulse stretching factors in the amplifier, which minimize the beam pathway in the compressor. The amplifier also integrates a versatile AOPDF (acousto-optic programmable dispersive filter) for closed-loop spectral phase optimization. The various factors influencing the overall phase stability of the system are discussed in detail. Using the optimized output, 1-mJ, 4.5-fs pulses are generated by seeding the neon gas filled hollow fiber with a circularly polarized input beam. A standard phase deviation of 230 mrad after the HCF is obtained by direct f-to-2f detection and slow-loop feedback to the oscillator locking electronics without any additional spectral broadening

    Front‐end of the ILE Project: A design study for a 100 mJ sub‐10 fs laser

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    International audienceWithin the development of the ILE French project aiming on the building of a 10 PW, 150 J∕15 fs laser chain (named APOLLON), a design study for a sub‐10‐fs, 100 mJ pilot laser operating at 800 nm have been conceived. This system is based on a non‐collinear optical parametric chirped‐pulse amplification (NOPCPA) of the spectrally broadened and compressed pulses of a Ti:Sapphire laser system providing 1.5‐mJ, 25‐fs, pumped at 515 nm by a high‐energy diode‐pumped Yb‐doped‐based laser chain. The envisioned system, based on a novel combined architecture of picosecond and nanosecond NOPCPA stages, will finally deliver carrier envelope phased (CEP) stabilized 1 ns pulses (compressible to less than 10 fs) at 800 nm with 100 mJ energy and at a repetition rate in the range of 10-100 Hz
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