Because existing therapeutic cancer vaccines provide only a limited clinical benefit, a different vaccination strategy is necessary to improve vaccine efficacy. We developed a nanoparticulate cancer vaccine by encapsulating a synthetic long peptide antigen within an immunologically inert nanoparticulate hydrogel (nanogel) of cholesteryl pullulan (CHP). After subcutaneous injection to mice, the nanogel-based vaccine was efficiently transported to the draining lymph node, and was preferentially engulfed by medullary macrophages but was not sensed by other macrophages and dendritic cells (so-called "immunologically stealth mode"). Although the function of medullary macrophages in T cell immunity has been unexplored so far, these macrophages effectively cross-primed the vaccine-specific CD8(+) T cells in the presence of a Toll-like receptor (TLR) agonist as an adjuvant. The nanogel-based vaccine significantly inhibited in vivo tumor growth in the prophylactic and therapeutic settings, compared to another vaccine formulation using a conventional delivery system, incomplete Freund's adjuvant. We also revealed that lymph node macrophages were highly responsive to TLR stimulation, which may underlie the potency of the macrophage-oriented, nanogel-based vaccine. These results indicate that targeting medullary macrophages using the immunologically stealth nanoparticulate delivery system is an effective vaccine strategy.
A systematic analysis of the deep level spectrum in the lower half of the bandgap of Au–Zn1−xMgxO (0.056<x<0.18) Schottky diodes is presented. Two deep levels are observed at Ev+580 and Ev+280 meV regardless of the bandgap energy with trap concentrations linearly increasing with the Mg content. The Ev+280 meV trap concentration becomes as high as 1.01×1018 cm−3 at 18% Mg, partially compensating the films and causing a decrease from 8.02×1016 to 1.27×1016 cm−3 in the net electron concentration and an increase by three orders of magnitude in the diode series resistance due to electron trapping.
Schottky photodiodes based on Au-ZnMgO/sapphire are demonstrated covering the spectral region from 3.35 to 3.48 eV, with UV/VIS rejection ratios up to ∼105 and responsivities as high as 185 A/W. Both the rejection ratio and the responsivity are shown to be largely enhanced by the presence of an internal gain mechanism, by which the compensated films become highly conductive as a result of illumination. This causes a large increase in the tunnel current through the Schottky barrier, yielding internal gains that are a function of the incident photon flux.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is the cause of novel coronavirus disease 2019 (COVID-19), was first reported in Wuhan, China, and now has spread across the world as a global pandemic. The propagation from asymptomatic polymerase chain reaction (PCR)-positive individuals represents a complicating factor in the efforts to control the COVID-19 pandemic. We examined the course of PCR assays and the duration of viral shedding in 23 asymptomatic or mild COVID-19 patients from the cruise ship who were admitted to our hospital. Among these 23 cases, the median duration of viral shedding was 19 days (range, 6-37 days) from initial viral detection. Eight cases (35%) had another positive PCR result after testing negative once. Although the duration of viral shedding was approximately three weeks, the infectivity and transmissibility period from asymptomatic and mild COVID-19 cases is unclear. Further studies are needed to determine how long such asymptomatic and mild COVID-19 cases have infectivity.
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