Increased in vivo immunological potency of HB-110, a novel therapeutic HBV DNA vaccine, by electroporation

Pulse-induced permeabilization of cellular membranes, generally referred to as electroporation (EP), has been used for years as a tool to increase macromolecule uptake in tissues, including nucleic acids, for gene therapeutic applications, and this technique has been shown to result in improved immunogenicity. In this study, we assessed the utility of EP as a tool to improve the efficacy of HB-110, a novel therapeutic DNA vaccine against chronic hepatitis B, now in phase 1 of clinical study in South Korea. The potency of HB-110 in mice was shown to be improved by EP. The rapid onset of antigen expression and higher magnitude of humoral and cellular responses in electric pulse-treated mice revealed that EP may enable a substantial reduction in the dosage of DNA vaccine required to elicit a response similar in magnitude to that achievable via conventional administration. This study also showed that EP-based vaccination at 4-week-intervals elicited a cellular immune response which was about two-fold higher than the response elicited by conventional vaccination at 2-week intervals. These results may provide a rationale to reduce the clinical dose and increase the interval between the doses in the multidose vaccination schedule. Electric pulsing also elicited a more balanced immune response against four antigens expressed by HB-110: S, preS, Core, and Pol.     

Electronic structure studies of Mg0.95Mn0.05Fe2−2xTi2xO4 (0x0.8)

The electronic structure of Mg_0.95Mn_0.05Fe_2−2xTi_2xO₄ (0x0.8) compound is investigated using near edge X-ray absorption fine structure, (NEXAFS) spectroscopy measurements, carried out at O K, Fe and Ti L_3,2-edges at room temperature. The O K-edge spectra indicate that the Fe 3d orbitals have been considerably modified and a new spectral feature start dominating in the pre-edge region at higher Ti doping. The Fe 2p NEXAFS spectra exhibit a mixed valent Fe²⁺/Fe³⁺ states apart from the conversion of Fe³⁺ to Fe²⁺ with the substitution of Ti ions. The Ti L_3,2-edge spectra indicate that Ti ions remain unchanged at 4+ state. These variations in the host electronic structure due to Ti substitution are consistent with the dielectric and transport properties of the material.     

Photoelectrochemical CO2 Reduction with a Rhenium Organometallic Redox Mediator at Semiconductor/Aqueous Liquid Junction Interfaces

Electrochemical and photoelectrochemical CO₂ reductions were carried out with Re(bh‐bipy)(CO)₃(OH₂) cocatalysts in aqueous electrolytes. Competition between hydrogen evolution and CO₂ reduction was observed under (photo)electrochemical conditions for both glassy carbon and CuInS₂ electrodes. The partial current density for CO generation is limited even though the additional potential is applied. However, electrochemical hydrogen evolution was suppressed under photoelectrochemical conditions, and the selectivity and partial current density for CO were considerably increased when compared to the electrochemical reduction in an identical electrode/electrolyte system. This finding may provide insights into using semiconductor/liquid junctions for solar fuel devices to overcome the limitations of electrolysis systems with an external bias.     

Heating factors of gas targets for radioactive ion beam production

At low-energy nuclear physics facilities, the in-flight fragmentation method is often employed to produce radioactive ion beams. This technique often involves a stable ion beam at high intensity and a gas cell target. Since the parameters for the production reaction are usually chosen to take advantage of a large cross section of the resonance reaction, a slight change in the center-of-mass energy due to the reduced target density may significantly affect the rare isotope production rate. Therefore, to estimate the heating effect due to beam particles on the target thickness, a new and more comprehensive semi-empirical model is developed by employing a heating factor function. The estimated heating factors were consistent with experimental data, which were obtained from various reaction measurements at wide ranges of heat densities.

     

Self‐Assembly Behaviors of a Penta‐Phenylene Maltoside and Its Application for Membrane Protein Study

We prepared an amphiphile with a penta‐phenylene lipophilic group and a branched trimaltoside head group. This new agent, designated penta‐phenylene maltoside (PPM), showed a marked tendency to self‐assembly into micelles via strong aromatic–aromatic interactions in aqueous media, as evidenced by ¹H NMR spectroscopy and fluorescence studies. When utilized for membrane protein studies, this new agent was superior to DDM, a gold standard conventional detergent, in stabilizing multiple proteins long term. The ability of this agent to form aromatic–aromatic interactions is likely responsible for enhanced protein stabilization when associated with a target membrane protein.     

Centrosome amplification and multinuclear phenotypes are Induced by hydrogen peroxide

Multinucleated cells resulted from mitosis defect have been noted in pathophysiological states of the cells such as inflammation, senescence and cancer. Since oxidative stress has been known to correlate with these pathophysiological conditions, we tested the effect of H2O2 on the cell cycle progression and formation of multinucleated cells. H2O2 induced a significant delay in cell cycle progression in Chang liver cells. Interestingly, H2O2 actively induced hyperamplification of centrosomes (n>or=3) and multipolar spindle formation during mitosis and subsequently increased the generation of multinucleated cells. A significant increase of the phospho-ERK level was observed upon H2O2 treatment but PD98059, an MEK1/2 inhibitor, didn't reduce the frequency of cells with hyperamplified centrosomes. On the other hand, treatment of either H2O2 or adriamycin increased intracellular ROS levels and multinucleated cells, which were significantly suppressed by antioxidants, N-acetylcysteine and PDTC. Thus, our results suggest that oxidative stress can trigger centrosome hyperamplification and multinucleated cell formation, which may promote pathophysiological progression.     

Evidence for microbunching "sidebands" in a saturated free-electron laser using coherent optical transition radiation

We report the first measurements of z-dependent coherent optical transition radiation (COTR) due to electron-beam microbunching at high gains ( >10(4)) including saturation of a self-amplified spontaneous emission free-electron laser (FEL). In these experiments the fundamental wavelength was near 530 nm, and the COTR spectra exhibit the transition from simple spectra to complex spectra ( 5% spectral width) after saturation. The COTR intensity growth and angular distribution data are reported as well as the evidence for transverse spectral dependencies and an "effective" core of the beam being involved in microbunching.