27 research outputs found

    TAROGE-M: radio antenna array on antarctic high mountain for detecting near-horizontal ultra-high energy air showers

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    Abstract The TAROGE-M radio observatory is a self-triggered antenna array on top of the ???2700 m high Mt. Melbourne in Antarctica, designed to detect impulsive geomagnetic emission from extensive air showers induced by ultra-high energy (UHE) particles beyond 1017 eV, including cosmic rays, Earth-skimming tau neutrinos, and particularly, the ???ANITA anomalous events??? (AAE) from near and below the horizon. The six AAE discovered by the ANITA experiment have signal features similar to tau neutrinos but that hypothesis is in tension either with the interaction length predicted by Standard Model or with the flux limits set by other experiments. Their origin remains uncertain, requiring more experimental inputs for clarification. The detection concept of TAROGE-M takes advantage of a high altitude with synoptic view toward the horizon as an efficient signal collector, and the radio quietness as well as strong and near vertical geomagnetic field in Antarctica, enhancing the relative radio signal strength. This approach has a low energy threshold, high duty cycle, and is easy to extend for quickly enlarging statistics. Here we report experimental results from the first TAROGE-M station deployed in January 2020, corresponding to approximately one month of livetime. The station consists of six receiving antennas operating at 180-450 MHz, and can reconstruct source directions of impulsive events with an angular resolution of ???0.3??, calibrated in situ with a drone-borne pulser system. To demonstrate TAROGE-M's ability to detect UHE air showers, a search for cosmic ray signals in 25.3-days of data together with the detection simulation were conducted, resulting in seven identified candidates. The detected events have a mean reconstructed energy of 0.95-0.31+0.46 EeV and zenith angles ranging from 25?? to 82??, with both distributions agreeing with the simulations, indicating an energy threshold at about 0.3 EeV. The estimated cosmic ray flux at that energy is 1.2-0.9+0.7 ?? 10-16 eV-1 km-2 yr-1 sr-1, also consistent with results of other experiments. The TAROGE-M sensitivity to AAEs is approximated by the tau neutrino exposure with simulations, which suggests comparable sensitivity as ANITA's at around 1 EeV energy with a few station-years of operation. These first results verified the station design and performance in a polar and high-altitude environment, and are promising for further discovery of tau neutrinos and AAEs after an extension in the near future

    Film-trigger applicator (FTA) for improved skin penetration of microneedle using punching force of carboxymethyl cellulose film acting as a microneedle applicator

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    Abstract Background Dissolving microneedle (DMN) is a transdermal drug delivery system that creates pore in the skin and directly deliver drug through the pore channel. DMN is considered as one of the promising system alternatives to injection because it is minimally invasive and free from needle-related issues. However, traditional DMN patch system has limitations of incomplete insertion and need of complex external devices. Here, we designed film-trigger applicator (FTA) system that successfully delivered DMN inside the skin layers using fracture energy of carboxymethyl cellulose (CMC) film via micropillars. We highlighted advantages of FTA system in DMN delivery compared with DMN patch, including that the film itself can act as DMN applicator. Methods FTA system consists of DMNs fabricated on the CMC film, DMN array holder having holes aligned to DMN array, and micropillars prepared using general purpose polystyrene. We analyzed punching force on the film by micropillars until the film puncture point at different CMC film concentrations and micropillar diameters. We also compared drug delivery efficiency using rhodamine B fluorescence diffusion and skin penetration using optical coherence tomography (OCT) of FTA with those of conventional DMN patch. In vivo experiments were conducted to evaluate DMN delivery efficiency using C57BL/6 mice and insulin as a model drug. Results FTA system showed enhanced delivery efficiency compared with that of the existing DMN patch system. We concluded CMC film as a successful DMN applicator as it showed enhanced DMN penetration in OCT and rhodamine B diffusion studies. Further, we applied FTA on shaved mouse dorsal skin and observed successful skin penetration. The FTA group showed higher level of plasma insulin in vivo than that of the DMN patch group. Conclusions FTA system consisting of simple polymer film and micropillars showed enhanced DMN delivery than that of the existing DMN patch system. Because FTA works with simple finger force without sticky patch and external devices, FTA is a novel and promising platform to overcome the limitations of conventional microneedle patch delivery system; we suggest FTA as a next generation applicator for microneedle application in the future

    Improvement of Biophysical Properties and Affinity of a Human Anti-L1CAM Therapeutic Antibody through Antibody Engineering Based on Computational Methods

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    The biophysical properties of therapeutic antibodies influence their manufacturability, efficacy, and safety. To develop an anti-cancer antibody, we previously generated a human monoclonal antibody (Ab417) that specifically binds to L1 cell adhesion molecule with a high affinity, and we validated its anti-tumor activity and mechanism of action in human cholangiocarcinoma xenograft models. In the present study, we aimed to improve the biophysical properties of Ab417. We designed 20 variants of Ab417 with reduced aggregation propensity, less potential post-translational modification (PTM) motifs, and the lowest predicted immunogenicity using computational methods. Next, we constructed these variants to analyze their expression levels and antigen-binding activities. One variant (Ab612)—which contains six substitutions for reduced surface hydrophobicity, removal of PTM, and change to the germline residue—exhibited an increased expression level and antigen-binding activity compared to Ab417. In further studies, compared to Ab417, Ab612 showed improved biophysical properties, including reduced aggregation propensity, increased stability, higher purification yield, lower pI, higher affinity, and greater in vivo anti-tumor efficacy. Additionally, we generated a highly productive and stable research cell bank (RCB) and scaled up the production process to 50 L, yielding 6.6 g/L of Ab612. The RCB will be used for preclinical development of Ab612

    Effect of ZnO and SnO2 Nanolayers at Grain Boundaries on Thermoelectric Properties of Polycrystalline Skutterudites

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    Nanostructuring is considered one of the key approaches to achieve highly efficient thermoelectric alloys by reducing thermal conductivity. In this study, we investigated the effect of oxide (ZnO and SnO2) nanolayers at the grain boundaries of polycrystalline In0.2Yb0.1Co4Sb12 skutterudites on their electrical and thermal transport properties. Skutterudite powders with oxide nanolayers were prepared by atomic layer deposition method, and the number of deposition cycles was varied to control the coating thickness. The coated powders were consolidated by spark plasma sintering. With increasing number of deposition cycle, the electrical conductivity gradually decreased, while the Seebeck coefficient changed insignificantly; this indicates that the carrier mobility decreased due to the oxide nanolayers. In contrast, the lattice thermal conductivity increased with an increase in the number of deposition cycles, demonstrating the reduction in phonon scattering by grain boundaries owing to the oxide nanolayers. Thus, we could easily control the thermoelectric properties of skutterudite materials through adjusting the oxide nanolayer by atomic layer deposition method
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