Novel mid-infrared dispersive wave generation in gas-filled PCF by transient ionization-driven changes in dispersion

Gas-filled hollow-core photonic crystal fibre (PCF) is being used to generate ever wider supercontinuum spectra, in particular via dispersive wave (DW) emission in the deep and vacuum ultraviolet, with a multitude of applications. DWs are the result of the resonant transfer of energy from a self-compressed soliton, a process which relies crucially on phase matching. It was recently predicted that, in the strong-field regime, the additional transient anomalous dispersion introduced by gas ionization would allow phase-matched DW generation in the mid-infrared (MIR)-something that is forbidden in the absence of free electrons. Here we report for the first time the experimental observation of such MIR DWs, embedded in a 4.7-octave-wide supercontinuum that uniquely reaches simultaneously to the vacuum ultraviolet, with up to 1.7 W of total average power

Generation of broadband mid-IR and UV light in gas-filled single-ring hollow-core PCF

We report generation of an ultrafast supercontinuum extending into the mid- infrared in gas-filled single-ring hollow-core photonic crystal fiber (SR-PCF) pumped by 1.7 $\mu$m light from an optical parametric amplifier. The simple fiber structure offers shallow dispersion and flat transmission in the near and mid-infrared, enabling the generation of broadband spectra extending from 300 nm to 3.1 $\mu$m, with a total energy of a few $\mu$J. In addition, we report the emission of ultraviolet dispersive waves whose frequency can be tuned simply by adjusting the pump wavelength. SR-PCF also provides an effective means of compressing and delivering tunable ultrafast pulses in the near and mid-infrared spectral regions.Comment: 7 pages, 4 figure

An Oral Vaccine Based on U-Omp19 Induces Protection against B. abortus Mucosal Challenge by Inducing an Adaptive IL-17 Immune Response in Mice

As Brucella infections occur mainly through mucosal surfaces, the development of mucosal administered vaccines could be radical for the control of brucellosis. In this work we evaluated the potential of Brucella abortus 19 kDa outer membrane protein (U-Omp19) as an edible subunit vaccine against brucellosis. We investigated the protective immune response elicited against oral B. abortus infection after vaccination of mice with leaves from transgenic plants expressing U-Omp19; or with plant-made or E. coli-made purified U-Omp19. All tested U-Omp19 formulations induced protection against Brucella when orally administered without the need of adjuvants. U-Omp19 also induced protection against a systemic challenge when parenterally administered. This built-in adjuvant ability of U-Omp19 was independent of TLR4 and could be explained at least in part by its capability to activate dendritic cells in vivo. While unadjuvanted U-Omp19 intraperitoneally administered induced a specific Th1 response, following U-Omp19 oral delivery a mixed specific Th1-Th17 response was induced. Depletion of CD4+ T cells in mice orally vaccinated with U-Omp19 resulted in a loss of the elicited protection, indicating that this cell type mediates immune protection. The role of IL-17 against Brucella infection has never been explored. In this study, we determined that if IL-17A was neutralized in vivo during the challenge period, the mucosal U-Omp19 vaccine did not confer mucosal protection. On the contrary, IL-17A neutralization during the infection did not influence at all the subsistence and growth of this bacterium in PBS-immunized mice. All together, our results indicate that an oral unadjuvanted vaccine based on U-Omp19 induces protection against a mucosal challenge with Brucella abortus by inducing an adaptive IL-17 immune response. They also indicate different and important new aspects i) IL-17 does not contribute to reduce the bacterial burden in non vaccinated mice and ii) IL-17 plays a central role in vaccine mediated anti-Brucella mucosal immunity

Characterization of Periplasmic Protein BP26 Epitopes of Brucella melitensis Reacting with Murine Monoclonal and Sheep Antibodies

More than 35,000 new cases of human brucellosis were reported in 2010 by the Chinese Center for Disease Control and Prevention. An attenuated B. melitensis vaccine M5-90 is currently used for vaccination of sheep and goats in China. In the study, a periplasmic protein BP26 from M5-90 was characterized for its epitope reactivity with mouse monoclonal and sheep antibodies. A total of 29 monoclonal antibodies (mAbs) against recombinant BP26 (rBP26) were produced, which were tested for reactivity with a panel of BP26 peptides, three truncated rBP26 and native BP26 containing membrane protein extracts (NMP) of B. melitensis M5-90 in ELISA and Western-Blot. The linear, semi-conformational and conformational epitopes from native BP26 were identified. Two linear epitopes recognized by mAbs were revealed by 28 of 16mer overlapping peptides, which were accurately mapped as the core motif of amino acid residues 93DRDLQTGGI101 (position 93 to 101) or residues 104QPIYVYPD111, respectively. The reactivity of linear epitope peptides, rBP26 and NMP was tested with 137 sheep sera by ELISAs, of which the two linear epitopes had 65–70% reactivity and NMP 90% consistent with the results of a combination of two standard serological tests. The results were helpful for evaluating the reactivity of BP26 antigen in M5-90

A Novel Bacterial Protease Inhibitor Adjuvant in RBD-Based COVID-19 Vaccine Formulations Containing Alum Increases Neutralizing Antibodies, Specific Germinal Center B Cells and Confers Protection Against SARS-CoV-2 Infection in Mice

In this work, we evaluated recombinant receptor binding domain (RBD)-based vaccine formulation prototypes with potential for further clinical development. We assessed different formulations containing RBD plus alum, AddaS03, AddaVax, or the combination of alum and U-Omp19: a novel Brucella spp. protease inhibitor vaccine adjuvant. Results show that the vaccine formulation composed of U-Omp19 and alum as adjuvants has a better performance: it significantly increased mucosal and systemic neutralizing antibodies in comparison to antigen plus alum, AddaVax, or AddaS03. Antibodies induced with the formulation containing U-Omp19 and alum not only increased their neutralization capacity against the ancestral virus but also cross-neutralized alpha, lambda, and gamma variants with similar potency. Furthermore, the addition of U-Omp19 to alum vaccine formulation increased the frequency of RBD-specific geminal center B cells and plasmablasts. Additionally, U-Omp19+alum formulation induced RBD-specific Th1 and CD8+ T-cell responses in spleens and lungs. Finally, this vaccine formulation conferred protection against an intranasal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) challenge of K18-hACE2 mice.Fil: Coria, Mirta Lorena. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Biotecnológicas; ArgentinaFil: Saposnik, Lucas Martín. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Biotecnológicas; ArgentinaFil: Pueblas Castro, Celeste Victoria. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Biotecnológicas; ArgentinaFil: Castro, Eliana Florencia. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Biotecnológicas; Argentina. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Virología e Innovaciones Tecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Virología e Innovaciones Tecnológicas; ArgentinaFil: Bruno, Laura Alejandra. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Biotecnológicas; ArgentinaFil: Stone, William B.. University of Virginia; Estados UnidosFil: Pérez, Paula Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Darriba, Maria Laura. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Biotecnológicas; ArgentinaFil: Chemes, Lucia Beatriz. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Biotecnológicas; ArgentinaFil: Alcain, Julieta María. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Biotecnológicas; ArgentinaFil: Mazzitelli, Ignacio Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Varese, Augusto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Salvatori, Melina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Auguste, Albert J.. University of Virginia; Estados UnidosFil: Alvarez, Diego Ezequiel. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Biotecnológicas; ArgentinaFil: Pasquevich, Karina Alejandra. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Biotecnológicas; ArgentinaFil: Cassataro, Juliana. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Biotecnológicas; Argentin

Photoionization-Induced Emission of Tunable Few-Cycle Midinfrared Dispersive Waves in Gas-Filled Hollow-Core Photonic Crystal Fibers

We propose a scheme for the emission of few-cycle dispersive waves in the midinfrared using hollow-core photonic crystal fibers filled with noble gas. The underlying mechanism is the formation of a plasma cloud by a self-compressed, subcycle pump pulse. The resulting free-electron population modifies the fiber dispersion, allowing phase-matched access to dispersive waves at otherwise inaccessible frequencies, well into the midinfrared. Remarkably, the pulses generated turn out to have durations of the order of two optical cycles. In addition, this ultrafast emission, which occurs even in the absence of a zero dispersion point between pump and midinfrared wavelengths, is tunable over a wide frequency range simply by adjusting the gas pressure. These theoretical results pave the way to a new generation of compact, fiber-based sources of few-cycle midinfrared radiation

Generation of broadband mid-IR and UV light in gas-filled single-ring hollow-core PCF

We report generation of an ultrafast supercontinuum extending into the mid-infrared in gas-filled single-ring hollow-core photonic crystal fiber (SR-PCF) pumped by 1.7 mu m light from an optical parametric amplifier. The simple fiber structure offers shallow dispersion and flat transmission in the near and mid-infrared, enabling the generation of broadband spectra extending from 270 nm to 3.1 mu m, with a total energy of a few mu J. In addition, we demonstrate the emission of ultraviolet dispersive waves whose frequency can be tuned simply by adjusting the pump wavelength. SR-PCF thus constitutes an effective means of compressing and delivering tunable ultrafast pulses in the near and mid-infrared spectral regions. (C) 2017 Optical Society of Americ

Analysis of genetic markers for the optimization of an individualized approach to osteoporosis.

Aim of this study: Osteoporosis is a systemic skeletal disease characterized by compromised bone structure and resistance and by an increased risk of fracture especially in postmenopausal women. Multiple factors including hormonal, environmental and genetic factors are involved in osteoporosis development and clinical outcome. It has been shown that Klotho and insulin-like growth factor-1 (IGF-1) have a significant effect on aging and osteoporosis risk. Actually, Insulin-like growth factor-1 (IGF-1) is a critical polypeptide that plays an important role in the regulation of bone metabolism, which promotes bone cell growth, differentiation, cell cycle progression. Klotho modulates aging in mice and humans, Klotho membrane-bound protein serves as a co-receptor required for the fibroblast growth factor 23 (FGF23), the link between Klotho and FGF23 creates a negative feedback that blocks the enzyme that converts 25-hydroxy Vitamin D to the active form (1,25 dihydroxy Vitamin D). Thus, klotho and FGF23 may function in a common signal transduction pathway in maintaining mineral ion homeostasis. Considering that some gene variant might influence production level and function of these mediators, we have started the evaluation of associations among IGF-1, IGF-1R and Klotho 1 SNPs and osteoporosis risk. Methods: In this preliminary approach, a total of 20 women with diagnosis of osteoporosis confirmed by radiograph or DEXA scan and a total of 72 healthy control women were included in the study. For the genetic analysis, peripheral blood samples were collected and genomic DNA was extracted from leukocytes. Genotypic analysis of polymorphisms of Klotho 1 (rs577912), IGF-1(rs35767), IGF-1R was conducted using a competitive allele specific PCR assays (KASpar) developed by Kbioscence. Genotype and allele frequencies were compared by statistical analysis using dominant, codominant, and recessive models. Results: In our study, the analysis of genotypic and allelic frequencies has highlighted, that IGF-I rs35767 genotypes positive for T allele are more represented in cases than in controls and could be associated with susceptibility to osteoporosis (P = 0.0327 OR= 4.529; 95% C.I.: 1.27 - 16.1). Instead, the SNP of Klotho 1 and IGF-I R have in our case subjects a frequency not different from that of the controls. Discussion and Conclusion: Our results are in full agreement with those from Zhang et al. (Genet Mol Res. 2015; 14: 7655-60) reporting association of T+ genotypes of rs35767 with lower BMD levels in the femoral neck. This preliminary result suggests that polymorphism in IGF-I rs35767 might play a role in osteoporosis risk and could be considered a potential indicator for risk of osteoporosis in postmenopausal women