Development of peptide vaccines in dengue

Dengue is one of the most important arboviral infection worldwide, infecting up to 390 million people and causing 25,000 deaths annually. Although a licensed dengue vaccine is available, it is not efficacious against dengue serotypes that infect people living in South East Asia, where dengue is an endemic disease. Hence, there is an urgent need to develop an efficient dengue vaccine for this region. Data from different clinical trials indicate that a successful dengue vaccine must elicit both neutralizing antibodies and cell mediated immunity. This can be achieved by designing a multi-epitope peptide vaccine comprising B, CD8+ and CD4+ T cell epitopes. As recognition of T cell epitopes are restricted by human leukocyte antigens (HLA), T cell epitopes which are able to recognize several major HLAs will be preferentially included in the vaccine design. While peptide vaccines are safe, biocompatible and cost-effective, it is poorly immunogenic. Strategies to improve its immunogenicity by the use of long peptides, adjuvants and nanoparticle delivery mechanisms are discusse

Enhancement of tetravalent immune responses to highly conserved epitopes of a dengue peptide vaccine conjugated to polystyrene nanoparticles

Vaccination remains the major approach to the prevention of dengue. Since the only licensed live attenuated vaccine (LAV) lacked efficacy against all four serotypes, other vaccine platforms, such as synthetic peptide vaccines, should be explored. In this study, four multi-epitope peptides (P1–P4)were designed by linking a universal T-helper epitope (PADREorTpD) to the highly conserved CD8 T cell epitope and B cell epitope (B1 or B2) against all four DENV serotypes. The multi-epitope peptides were conjugated to polystyrene nanoparticles (PSNPs) and four nanovaccines (NP1–NP4) were constructed. Mice immunized with NP1–NP4 elicited significantly higher titers of IgG and neutralizing antibodies when compared to immunization with naked P1–P4. The immune responses in mice immunized with peptide vaccines were compared with nanovaccines using ELISA, ELISPOT, and a neutralization test based on FRNT50. Among the four conjugated peptide nanovaccines, NP3comprisingtheTpDT-helper epitope linked to the highly conserved B1 epitope derived from the E protein was able to elicit significant levels of IFN-γ and neutralizing antibodies to all four dengue serotypes. NP3 is a promising tetravalent synthetic peptide vaccine, but the selection of a more effective CD8+ T cell epitope and adjuvants to further improve the immunogenicity is warranted

Search for Eccentric Black Hole Coalescences during the Third Observing Run of LIGO and Virgo

Despite the growing number of confident binary black hole coalescences observed through gravitational waves so far, the astrophysical origin of these binaries remains uncertain. Orbital eccentricity is one of the clearest tracers of binary formation channels. Identifying binary eccentricity, however, remains challenging due to the limited availability of gravitational waveforms that include effects of eccentricity. Here, we present observational results for a waveform-independent search sensitive to eccentric black hole coalescences, covering the third observing run (O3) of the LIGO and Virgo detectors. We identified no new high-significance candidates beyond those that were already identified with searches focusing on quasi-circular binaries. We determine the sensitivity of our search to high-mass (total mass $M>70$ $M_\odot$) binaries covering eccentricities up to 0.3 at 15 Hz orbital frequency, and use this to compare model predictions to search results. Assuming all detections are indeed quasi-circular, for our fiducial population model, we place an upper limit for the merger rate density of high-mass binaries with eccentricities $0 < e \leq 0.3$ at $0.33$ Gpc$^{-3}$ yr$^{-1}$ at 90\% confidence level.Comment: 24 pages, 5 figure

Search for eccentric black hole coalescences during the third observing run of LIGO and Virgo

Despite the growing number of confident binary black hole coalescences observed through gravitational waves so far, the astrophysical origin of these binaries remains uncertain. Orbital eccentricity is one of the clearest tracers of binary formation channels. Identifying binary eccentricity, however, remains challenging due to the limited availability of gravitational waveforms that include effects of eccentricity. Here, we present observational results for a waveform-independent search sensitive to eccentric black hole coalescences, covering the third observing run (O3) of the LIGO and Virgo detectors. We identified no new high-significance candidates beyond those that were already identified with searches focusing on quasi-circular binaries. We determine the sensitivity of our search to high-mass (total mass M&gt;70 M⊙) binaries covering eccentricities up to 0.3 at 15 Hz orbital frequency, and use this to compare model predictions to search results. Assuming all detections are indeed quasi-circular, for our fiducial population model, we place an upper limit for the merger rate density of high-mass binaries with eccentricities 0&lt;e≤0.3 at 0.33 Gpc−3 yr−1 at 90\% confidence level

ZIF-8 derived CeO₂-Fe₃O₄@Fe-N/C catalyst for oxygen reduction reaction

Looking for non-noble metal catalysts with low cost, high activity, and high stability to replace platinum in oxygen reduction reaction (ORR) has aroused great concern. According to previous studies, Fe-Nx/C material is one of the most promising non-noble metal catalysts for ORR. In this study, new Fe-Nx/C material was synthesized by introducing CeO2 and Fe3O4 nanoparticles into a Fe-Nx/C material derived from ZIF-8 as precursors. The new material was called CeO2-Fe3O4@Fe-N/C catalyst and the activity of the catalyst was found to be significantly improved in 0.1 mol L−1 KOH. The half-wave potential of CeO2-Fe3O4@Fe-N/C (0.892 V) is higher than that of Pt/C by 67 mV. In the stability test, the half-wave potential of CeO2-Fe3O4@Fe-N/C was only reduced by 4 mV after 5,000 cycles. The high performance is attributed to the introduction of CeO2 and Fe3O4, which gives CeO2-Fe3O4@Fe-N/C enhanced electrocatalytic activity and long-term stability. This approach makes CeO2-Fe3O4@Fe-N/C a promising candidate for cathode catalysts in renewable energy conversion devices.The project was financially supported by a research grant (204-A018001) from the China-Singapore International Joint Research Institute

The Implementation Gap: Environmental Rhetoric Versus Reality in Lao Cai, Vietnam

International audienceThis study draws upon a case study of Lao Cai, a province recognized as one of the most important ecological regions in Vietnam, but also one of the most vulnerable to climate hazards. The province has recently adopted an action plan for climate change adaptation. However, the national authorities intend to promote Lao Cai as a major secondary city on the main route from China to Hanoi. In a context of rapid, strategic, state-driven urban development, I identify three main obstacles to effective implementation of environmental and climate change policies: (1) the pre-eminence of economic growth over any environmental goal, (2) the under- enforcement of existing regulations, and (3) a failure of environmental governance. Environmental risk management is mainly based on the reinforcement of defensive infrastructures (such as the river embankment) and the displacement of exposed people. These actions are likely inefficient in a context of increased major hazards that might put great pressure on displaced residents’ livelihoods. In other words, there is a wide gap between discourse and implementation