Anti-invasive activity of α-tocopherol against hepatoma cells in culture via protein kinase C inhibition

Effects of α-, β-, γ- and δ-tocopherols on the proliferation and invasion of AH109A hepatoma cells and their modes of action were investigated. Four tocopherols inhibited the invasion as well as the proliferation of AH109A cells. Their inhibitory effects were more prominent on the invasion than on the proliferation. At 1 µM, α-tocopherol showed most potent anti-invasive activity without any influence on the proliferation. We have previously demonstrated that reactive oxygen species increase the invasion of AH109A cells. α-Tocopherol suppressed the reactive oxygen species-induced invasion but failed to suppress the reactive oxygen species-induced rises in intracellular peroxide level. GF 109203X, a protein kinase C inhibitor, decreased the invasive activity of AH109A cells. In contrast, phorbol-12-myristate-13-acetate, a protein kinase C activator, increased the invasive capacity of AH109A cells. α-Tocopherol suppressed the phorbol-12-myristate-13-acetate-induced increase in the invasion, and canceled the phorbol-12-myristate-13-acetate-induced rises in protein kinase C activity and phosphorylation of extracellular signal-regulated kinase. These results suggest that tocopherols, especially α-tocopherol, possess inhibitory effect more strongly on the invasion of AH109A cells than on the proliferation. They also suggest that the anti-invasive activity of α-tocopherol is raised through suppression of PKC/ERK signaling

Dual-Matrix Domain-Wall: A Novel Technique for Generating Permutations by QUBO and Ising Models with Quadratic Sizes

The Ising model is defined by an objective function using a quadratic formula of qubit variables. The problem of an Ising model aims to determine the qubit values of the variables that minimize the objective function, and many optimization problems can be reduced to this problem. In this paper, we focus on optimization problems related to permutations, where the goal is to find the optimal permutation out of the $n!$ possible permutations of $n$ elements. To represent these problems as Ising models, a commonly employed approach is to use a kernel that utilizes one-hot encoding to find any one of the $n!$ permutations as the optimal solution. However, this kernel contains a large number of quadratic terms and high absolute coefficient values. The main contribution of this paper is the introduction of a novel permutation encoding technique called dual-matrix domain-wall, which significantly reduces the number of quadratic terms and the maximum absolute coefficient values in the kernel. Surprisingly, our dual-matrix domain-wall encoding reduces the quadratic term count and maximum absolute coefficient values from $n^3-n^2$ and $2n-4$ to $6n^2-12n+4$ and $2$, respectively. We also demonstrate the applicability of our encoding technique to partial permutations and Quadratic Unconstrained Binary Optimization (QUBO) models. Furthermore, we discuss a family of permutation problems that can be efficiently implemented using Ising/QUBO models with our dual-matrix domain-wall encoding.Comment: 26 pages, 9 figure

Anti-inflammatory Nanomedicine for Cardiovascular Disease

Coronary artery disease, in the development of which inflammation mediated by innate immune cells plays a critical role, is one of the leading causes of death worldwide. The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) are a widely used lipid-lowering drug that has lipid-independent vasculoprotective effects, such as improvement of endothelial dysfunction, antioxidant properties, and inhibitory effects on inflammation. Despite recent advances in lipid-lowering therapy, clinical trials of statins suggest that anti-inflammatory therapy beyond lipid-lowering therapy is indispensible to further reduce cardiovascular events. One possible therapeutic option to the residual risk is to directly intervene in the inflammatory process by utilizing a nanotechnology-based drug delivery system (nano-DDS). Various nano-sized materials are currently developed as DDS, including micelles, liposomes, polymeric nanoparticles, dendrimers, carbon nanotubes, and metallic nanoparticles. The application of nano-DDS to coronary artery disease is a feasible strategy since the inflammatory milieu enhances incorporation of nano-sized materials into mononuclear phagocytic system and permeability of target lesions, which confers nano-DDS on “passive-targeting” property. Recently, we have developed a polymeric nanoparticle-incorporating statin to maximize its anti-inflammatory property. This statin nanoparticle has been tested in various disease models, including plaque destabilization and rupture, myocardial ischemia-reperfusion injury, and ventricular remodeling after acute myocardial infarction, and its clinical application is in progress. In this review, we present current development of DDS and future perspective on the application of anti-inflammatory nanomedicine to treat life-threatening cardiovascular diseases

Direct measurement of spectral shape of Cherenkov light using cosmic muons

The spectral pulse shape of Cherenkov lights was directly measured by using cosmic muons. The observed decay times for early and late timing were 5.0 and 5.2ns, respectively. They were actually shorter than the time of scintillation lights which were also measured as 9.3ns and 9.2ns, respectively. However we could not see the difference of the rise time between scintillation and Cherenkov lights. This was due to the slow response of our DAQ equipment, photomultiplier and FADC digitize

Precise pulse shape measurement of Cherenkov light using sub-MeV electrons from Sr-90/Y-90 beta source

The precise spectral pulse shape from Cherenkov lights was directly measured by using sub-MeV electrons from 90Sr/90Y beta source. The observed shape was clearly different from the shape of scintillation light. The pulse rise and fall （decay） time for Cherenkov light were 0.8 ns and 2.5 ns, respectively. They were actually shorter than those times of scintillation light which were also measured by 1.6 ns and 6.5 ns, respectively. This clear Thisclearclear difference of rise time will be used for the pulse shape discrimination in order to select PMTs which receive Cherenkov lights, and the topological information due to Cherenkov light will be used for the reduction of backgrounds from 208Tl beta decay which should be major backgrounds observed around Q-value （3.35MeV）of 96Zr neutrinoless double beta decay

HUN-ZICOS 検出器を用いたチェレンコフ光の位相幾何学情報の直接観測

The topological information of Cherenkov light from low energy electron was directly measured by HUNIZICOS detector. A 1.484 MeV electron with fixed direction to the center of hemispherical surface of the detector was generated by Compton back scattering with 100 degree from 88Y 1.836 MeV gamma. The observed averaged angle of Cherenkov light emitted from this electron was clustered around 40 degree assuming the vertex position to be at the center of truncated icosahedron photomultiplier jig. It was not Cherenkov angle around 47 degree as obtained by old simulation and the vertex to be the center of light yield for hitted photomultiplier. According to the HUNI-ZICOS simulation, the averaged angle of Cherenkov light was also clustered around 40 degree. On the other hands, the simulated averaged angle of scintillation was clustered around 49 degree, which is consistent with the averaged value of angle between the direction to center of hemisphere surface and each photomultiplier from the center of the jig. The obtained hitmap seemed to have same non flat structure as that of simulation due to Cherenkov ring. This is an evidence that Cherenkov lights emitted from 1.484 MeV electron should really have their topology. Therefore, we concluded that we will be able to reduce 208Tl background using the averaged angle for 96Zr neutrinoless double beta decay search.HUNI-ZICOS検出器を用いて低エネルギー電子が放出するチェレンコフ光の位相幾何学情報の直接観測を行った。単一方向・単色エネルギーを持つ電子を用いてチェレンコフ光の均角を観測したところ、光電子増倍管を設置する切頂20面体の治具の中心をバーテックスと仮定すると、40度に事象が集中していた。また、シミュレーションによると、チェレンコフ光の平均角は同様に40度に集中していた。これに対して、シンチレーション光の平均角は49度に集中していた。これは、切頂20面体の中心から半球の中心方向と、各光電子増倍管との間の角度の平均値と一致している。また、観測された光電子増倍管のヒットマップはチェレンコフ光リングにより一定の構造にはなっておらず、シミュレーションのヒットマップの構造とも合致している。これらの事実は、低エネルギー電子から放射されたチェレンコフ光は位相幾何学情報を維持していることの証拠である。つまり、平均角を用いればニュートリノを放出しない二重ベータ崩壊事象の探索で問題となる208Tlの背景事象を除去できると結論づけた

Effects of fly ash on NOx removal by pulsed streamers

NOx removal methods using plasma chemical reactions in nonthermal plasmas have been widely studied. In this paper, the effects of the addition of fly ash on NOx removal using short-pulsed discharge plasmas are described. Fly ash which had been collected from a coal-burning thermal electrical power plant was used. Experiments were performed using four different mixtures of gases which included NO. These were (N2+NO), (N2+NO+O2), (N2+NO+H2O), and (N2+NO+O2+H 2O). These gas mixtures were used either with or without the addition of fly ash. The initial concentration of NO was fixed at 200 ppm (NO parts per million of the gas mixture), The study of the NOx (NO+NO2) removal was performed with the fly ash, as it is relevant to real situations in coal power plants. The results show that the presence of fly ash decreased the NOx removal rate slightly in the case of dry gas mixtures while it increased the NOx removal rate substantially in the case of wet gas mixtures. These results suggest that the presence of fly ash in the flue gases, which also contain a few percentages of moisture, would be advantageous to the treatment of flue gases emitted from thermal power plants for the removal of nitrogen oxides

Influence of Gas Flow Rate and Reactor Length on NO Removal Using Pulsed Power

A short duration of 100-ns pulsed power has been used to remove nitric oxide (NO) in a mixture of nitrogen, oxygen, water vapor, and NO, simulating flue gases from a power station. The effects of the gas flow rate, the reactor length, and the pulse repetition rate on the percentage of NO removal and its energy efficiency are reported. The percentage of NO removal at a fixed gas flow rate increased with increasing pulse repetition rate due to the increased energy into the discharge. At a fixed pulse rate, the removal of NO increased with decreasing gas flow rate due to the increased residence time of the gas in the discharge reactor, thus facilitating the creation of increased radicals of O and N which then decreased NO. The energy removal efficiency of NO (in mol/kWh) decreased with increasing gas flow rate and increasing removal ratio of NO. The removal of NO increased with increasing energy density (J/I) input into the discharge at different reactor length

Development of pulse shape discrimination for Cherenkov lights in liquid scintillator

With a liquid scintillation used for ZICOS experiment, we measured pulse shapes in case of several radio isotopes, 60Co, 137Cs, 133Ba, and 57Co. Taking FADC timing at 60 nsec for the peak position, FADC spectra from 58.5 nsec to 80 nsec were almost same shape for each RI, however, before 58.5 nsec, we have found that those were different shape. Especially, in case of 57Co, the energy is lower than Cherenkov threshold, so that the spectra should not include Cherenkov light. Using those spectra between 57.0 nsec and 58.0 nsec（3 bins）, we calculated simply χ2 and it was clearly discriminated that χ2 ≥ 0.1 should be include Cherenkov lights. This was also confirmed by Compton electrons with fixed energy and fixed direction. Obtained detection inefficiency of Cherenkov lights was observed by 21.4 ± 9.6 %. According to Compton edge events which have almost same direction as the incident γ and backgrounds events which should have isotropic direction, the detection inefficiency were 10.4 ± 0.5 % and 49.1 ± 1.4 %, respectively. They were quite different values and the inefficiency of both fixed energy and Compton edge events were statistically same. This is a direct evidence that Cherenkov lights should keep their topology even if they are emitted by around 1 MeV electron

Production of Nitric Monoxide Using Pulsed Discharges for a Medical Application

Nitric monoxide (NO) is widely used in medical treatment of acute respiratory distress syndrome (ARDS). The production of NO is of interest to the medical community. In the present work, NO is generated by pulsed discharges between two rod electrodes in a mixture of nitrogen and oxygen. An arc discharge having a temperature of about 10000K was produced, which was sufficient to generate NO. Some of the important parameters affecting the production of NO have been investigated. These include the percentage of O2 (6-94%) in the mixture of N2 and O2, the energy of the discharge (0.5-12 J/pulse), the pulse repetition rate (0.5-4.5 pps) and the flow rate (1.35-5.4 l/min) of the gas mixture. NO2 produced in the discharge was successfully changed to NO using a heated molybdenum tube. NO2 must be extracted from the gas before clinical inhalation. The concentration of ozone was completely eliminated by bubbling the gas mixture through water. A maximum of NO and a minimum of NO2 concentrations were generated when the proportion of O2 in the gas mixture was in the range of 20-27%. The concentrations of NO and NO2 increased with increasing pulse repetition rate and with decreasing flow rate of the mixture. In all cases, NO2 was effectively removed using a heated molybdenum tube