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Covid-19 virus variants identified so far are due to viral genetic diversity, genetic evolution, and variable infectivity, suggesting that high infection rates and high mortality rates may be contributed by these mutations. And it has been reported that the targeting strategies for innate immunity should be less vulnerable to viral evolution, variant emergence and resistance. Therefore, the most effective solution to Covid-19 infection has been proposed to prevent and treat severe exacerbation of patients with moderate disease by enhancing human immune responses such as NK cell and T cell. In previous studies, we demonstrated for the first time that γ-PGA induced significant antitumor activity and antiviral activity by modulating NK cell-mediated cytotoxicity. Especially intranasal administration of γ-PGA was found to effectively induce protective innate and CTL immune responses against viruses and we found out that γ-PGA can be an effective treatment for cervical intraepithelial neoplasia 1 through phase 2b clinical trial. In this study, the possibility of γ-PGA as a Covid-19 immune modulating agent was confirmed by animal experiments infected with Covid-19 viruses. After oral administration of γ-PGA 300μg/mouse once a day for 5 days in a K18-hACE2 TG mouse model infected with SARS-CoV-2 (NCCP 43326; original strain) and SARS-CoV-2 (NCCP 43390; Delta variant), virus titer and clinical symptom improvement were confirmed. In the RjHan:AURA Syrian hamster model infected with SARS-CoV-2 (NCCP 49930; Delta variant), 350 or 550 μg/head of γ-PGA was administered orally for 10 days once a day. The virus for infection was administered at 5 × 104 TCID50, and the titer of virus and the improvement of pneumonia lesions were measured to confirm the effectiveness in terms of prevention or treatment. In the mouse model infected with original Covid-19 virus stain, the weight loss was significantly reduced and the survival rate was also improved by the administration of γ-PGA. And γ-PGA alleviated the pneumonic lesions and reduced the virus titer of lung tissue in mice infected with delta variant. In the delta-variant virus infected hamster model, γ-PGA showed statistically significant improvement of weight loss and lung inflammation during administration after infection. This is a promising result for possibility of Covid-19 therapeutics along with the efficacy results of mouse model, suggesting γ-PGA can be therapeutic candidate to modulate an innate immune response for Covid-19. Citation Format: Chan-Hee Yoo, Jae Chul Choi, Do Young Lee, Chun-Soo Lee, Young-Chul Park. Repurposing of poly-γ-glutamic acid, immunotherapeutic drug for cervical intraepithelial neoplasia 1, as covid-19 treatment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 794.

A hexaaluminate support was prepared by a co-precipitation method, and a metal (Cu, Pt, or Ir) was impregnated on the support to prepare a powdered catalyst. After that, organic and inorganic binders were added to the powdery catalyst and then pellets were formed. The so-formed catalysts were heat-treated at 1200°C, and their physicochemical properties were analyzed by N2-adsorption, X-ray diffraction (XRD), X-ray fluorenscence (XRF), and scanning electron microscopy (SEM). The decomposition activity of the catalysts on an ammonium dinitramide (ADN)-based liquid propellant was evaluated repeatedly, and the effects of catalyst composition and morphology on low temperature decomposition activity and durability were investigated. It was confirmed that the Cu-hexa-pellet, Pt-hexa-pellet, and Ir-hexa-pellet catalysts could be recovered and reused as a catalyst for decomposition of an ADN-based liquid monopropellant. The initial activity and the thermal stability of the Cu-hexa-pellet catalyst for the decomposition of ADN-based liquid monopropellants were better than for the other catalysts. The better activity of the Cu-hexa-pellet catalyst seems to be because the dispersion of the copper was higher than the metal dispersion in the other two catalysts.

The garment industry, which is traditionally labour-intensive, is facing significant challenges to reduce production costs in the face of material, labour, and infrastructure maintenance cost incre...

Green hypergolic propellants have been extensively studied. In the present study, we attempted to improve the measurement technique for the ignition delay in hypergolic reactions by using a drop-test apparatus. The evaluation method for the hypergolicity is important because an increase in the diversification of green hypergolic combinations is inevitable. Hydrogen peroxide (90 wt%) was used as an oxidizer, and six different reactive fuels were prepared. Sodium borohydride was utilized as an ignition source for the fuels. Optical and acoustic sensors were employed to reliably measure the ignition delay. The proposed measurement technique used in this study accurately reflected the physical phenomena of the hypergolic interactions. The technical limitations in the conventional measurement technique using a high-speed camera were experimentally investigated. Liquid-phase reactions were dominant in the hypergolic reactions of the glyme-based reactive fuels. Gas-phase reactions significantly influenced the hypergolic reactions of most of the amine-based reactive fuels. The pyridine-based reactive fuel had a longer delay time for the gas-phase reaction process than the liquid-phase reaction process. Recognizing the rate-determining step of the hypergolic ignition is necessary for not only designing a rocket injector but also reducing combustion instability, e.g., reactive stream separation.

To enable Small and Medium-sized Enterprises (SMEs) level garment manufacturers to measure and monitor the work of individual workers without incurring a large financial burden, a smart sewing work...

We investigated the influence of a copper loading strategy over hexaaluminate on catalytic performance during the decomposition of an ammonium dinitramide (ADN)-based liquid propellant. Powder-type and pellet-type Cu/hexaaluminate catalysts were prepared and their chemico-physical properties were characterized by N2 adsorption, XRD, and XRF. A Cu-hexa-pellet-A catalyst in which copper atoms are positioned inside the hexaaluminate matrix showed the lowest decomposition onset temperature in decomposition of an ADN-based propellant The excellent activity of the Cu-hexa-pellet-A catalyst is ascribed to copper being well incorporated in the hexaaluminate matrix, and the dispersion of the copper is higher than that in two other catalysts. When a thermal shock was applied at a high temperature of 1,200 °C prior to catalyst reuse, physical properties such as surface area, average pore diameter, and the compressive strength of the fresh catalyst did not deteriorate remarkably after five times repetitive reuse and heat treatment. Consequently, the Cu-hexa-pellet-A catalyst was confirmed to be a catalyst that has excellent activity and heat resistance simultaneously in decomposition of an ADN-based propellant.

27-Hydroxycholesterol (27OHChol) is a bioactive molecule that induces monocytic cell activation and differentiation and thereby participates in immune responses under hypercholesterolemic condition. However, it is unknown whether cyclosporin A (CsA), an immunosuppressant, affects biological effects of 27OHChol. In this study, we investigated whether CsA alters 27OHChol-induced cellular and molecular responses using the human monocyte/macrophage THP-1 cells. Treatment of the cells with CsA resulted in decreased expression of the mDC-specific markers (CD80, CD83 and CD88) induced by 27OHChol. Reduced endocytic activity recovered in the presence of CsA. The drug also inhibited the expressions of MHC class I and II molecules and CD197, a homing molecule of mDCs. We further investigated the outcomes of CsA treatment on the expression of M1 polarization markers and CD14, a component of the innate immune system. The drug decreased transcript levels of genes associated with the M1 polarization of monocytic cells, including CCL2, as well as expression of CD14 and MMP-9 which is involved in soluble CD14 shedding. Taken together, these results indicate that CsA inhibits the 27OHChol-induced differentiation and activation of monocytic cells into a mature dendritic cell (mDC) type and an immuno-stimulatory M1 subset, respectively, thereby modifying immune responses in a milieu rich in cholesterol and oxidized cholesterol molecules.

Implementing digital transformation in the garment industry is very difficult, owing to its labor-intensive structural characteristics. Further, the productivity of a garment production system is considerably influenced by a combination of processes and operators. This study proposes a simulation-based hybrid optimization method to maximize the productivity of a garment production line. The simulation reflects the actual site characteristics, i.e., process and operator level indices, and the optimization process reflects constraints based on expert knowledge. The optimization process derives an optimal operator sequence through a genetic algorithm (GA) and sequentially removes bottlenecks through workload analysis based on the results. The proposed simulation optimization (SO) method improved productivity by ∼67.4%, which is 52.3% higher than that obtained by the existing meta-heuristic algorithm. The correlation between workload and production was verified by analyzing the workload change trends. This study holds significance because it presents a new simulation-based optimization model that further applies the workload distribution method by eliminating bottlenecks and digitizing garment production lines.

The objective of this study is to elucidate the catalytic performance of hexaaluminate catalysts incorporating Cu and Ir simultaneously during the decomposition of an ammonium dinitramide (ADN)-based liquid propellant. Pellet-type catalysts were prepared and their chemico-physical properties were characterized by N2 adsorption, XRD, and XRF. It was confirmed that Cu and Ir atoms are well incorporated inside the hexaaluminate matrix of the Cu(x)Ir(10-x)-hexaaluminate catalysts and the content of Ir incorporated into hexaaluminte matrix was in the range of 2.5–8.2 wt%. The Cu(7)Ir(3)-hexaaluminate catalyst showed excellent activity in decomposition of ADN-based liquid monopropellant. The activity of the Cu(7)Ir(3)-hexaaluminate catalyst was much higher than that of the Cu(7)Ir(3)/hexaaluminate-imp catalyst prepared by impregnation of Cu and Ir onto the hexaaluminate pellet surface. This is attributed to the Cu and Ir being well incorporated in the hexaaluminate matrix and the dispersion of the Cu and Ir being greater in the Cu(7)Ir(3)-hexaaluminate than in the Cu(7)Ir(3)/hexaaluminate-imp.

The inspection of sewing defects is an essential step in the quality assurance of garment manufacturing. Although traditional automated defect detection applications have shown good performance, these methods are usually configured with handcrafted features designed by a human operator. Recently, deep learning methods that include Convolutional Neural Networks (CNNs) have demonstrated excellent performance in a wide variety of computer-vision applications. To take advantage of the CNN’s feature representation, the direct utilization of feature maps from the convolutional layers as universal feature descriptors has been studied. In this paper, we propose a sewing defect detection method using a CNN feature map extracted from the initial layers of a pre-trained VGG-16 to detect a broken stitch from a captured image of a sewing operation. To assess the effectiveness of the proposed method, experiments were conducted on a set of sewing images, including normal images, their synthetic defects, and rotated images. As a result, the proposed method detected true defects with 92.3% accuracy. Moreover, additional conditions for computing devices and deep learning libraries were investigated to reduce the computing time required for real-time computation. Using a general and cheap single-board computer with resizing the image and utilizing a lightweight deep learning library, the computing time was 0.22 s. The results confirm the feasibility of the proposed method’s performance as an appropriate manufacturing technology for garment production.

Scalable synthesis of high purities ammonium dinitramide (ADN), 98.2% or more has been performed through conversion of potassium dinitramide (KDN) into ammonium dinitramide using guanylurea dinitramide (GUDN) as a precursor, which can be scalable up to a few hundred grams. The obtained ADN and corresponding liquid ADN blended with fuel was subject to the decomposition reaction with and without iridium catalyst. The result of the decomposition reaction suggested that the blending of methanol with ADN gave a high performance. It has been shown that the presence of ammonium hydroxide in the blend maintained pH around 10 and also stabilized the ADN solution for more than 20 day at 60 °C.

Background - Despite preventive HPV vaccines is implemented worldwide, current treatments for high grade cervical intraepithelial neoplasia are ablative, and no pharmacological treatments are available. Here we evaluated safety of BLS-ILB-E710c, HPV 16 E7-expressing Lactobacillus-based vaccine, and explored its efficacy for histopathological regression in women with CIN2/3. Methods - Safety and efficacy of BLS-ILB-E710c were assessed in CIN2/3 associated with HPV16 and its related HPV types in a randomized, double-blind, placebo-controlled phase 2b study. Total of 116 patients was recruited from fourteen hospitals in South Korea, and were randomized (2:1) to receive 1000 mg BLS-ILB-E710c or placebo for 5 days at 1, 2, 4, and 8 weeks. The primary endpoint was histopathological regression to CIN1 or normal pathology at 16 weeks after the first dose. Full analysis set (FAS) and Per-protocol set (PPS) analyses were based on patients receiving at least one oral vaccination, and on patients receiving four rounds of oral vaccination without protocol violations, respectively. The safety population included all patients who enrolled. The trial is registered at clinicaltrials.gov (number NCT03274206). Findings - Total of 116 patients were randomized, and 113 received either BLS-ILB-E710c (n=75) or placebo (n=38). The oral vaccination was well tolerated and no serious vaccine-related AEs occurred. No differences were showed between the BLS-ILB-E710c and placebo groups for patient background and adverse events. In the full analysis set (FAS) no statistically significant difference was noted between the two groups of histopathological regression at 16 weeks. However, the distribution by Bethesda system (for cervical cytology) in CIN2 patients showed significant differences between two groups (P=0.0304), which can affect histopathological regression. Sub-group analysis in FAS is performed to reduce the bias; histopathological classification (CIN2, CIN3) and cytological classification (≤ASCUS, LSIL, HISL). Therefore, in CIN3 sub-group, BLS-ILB-E710c recipients showed 13.33% of higher histopathological regression at 32 weeks than placebo recipients, and interestingly represented the statistically significant difference when histopathological regression at 32 weeks compared with 16 weeks (percentage point difference 34.87 [95% CI 7.78–61.96]; P=0.0216). In BLS-ILB-E710c recipients of CIN3 sub-group with histopathological regression, E7-specific CD8+ T lymphocyte immune responses were induced at 32 weeks (P= 0.0323). In addition, in HSIL sub-group, BLS-ILB-E710c recipients showed higher histopathological regression at 32 weeks than placebo recipients in similar with CIN3 sub-group analysis. Interpretation – Based on the finding this study, BLS-ILB-E710c could induce the local immune response by recruiting HPV16 E7-specific CD8+ T cells to cervical lesions, leading to histologic regression. To assess the efficacy of BLS-ILB-E710c as a novel Lactobacillus-based oral vaccine, it is necessary to define the population and time frame for phase 3 trial. Citation Format: Jae Kwan Lee, Seung Hun Song, Young Tae Kim, Chi-Heum Cho, Chan Joo Kim, Young-Chul Park. A double-blind randomized, placebo-controlled trial of oral administration with human papillomavirus (HPV) type 16 E7-expressing Lactobacillus-based vaccine, BLS-ILB-E710c, for the treatment of cervical intraepithelial neoplasia (CIN2/3) [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2021 Oct 7-10. Philadelphia (PA): AACR; Mol Cancer Ther 2021;20(12 Suppl):Abstract nr P043.

Anthocyanins, one of the major plant pigments, are responsible for the coloration of various plant tissues and organs, including fruits. They are known to have significant health benefits. Anthocyanin biosynthesis is influenced by environmental factors such as cold temperature and is transcriptionally regulated by MYB/bHLH/WD40 complexes composed of R2R3-MYB, basic helix-loop-helix (bHLH), and WD40-type transcription factors (TFs). The Ruby locus, which encodes a MYB TF, controls anthocyanin production in the fruit of blood orange varieties in a dominant manner. For the marker-assisted selection of citrus breeding lines with high anthocyanin production, we established PCR-based molecular markers for robust genotyping of Ruby locus alleles. Two dominant Ruby alleles, RD-1 and RD-2, were specifically detected in the blood orange varieties with high anthocyanin contents in their fruit flesh, but not in the varieties rich in lycopene. For functional analysis of Ruby alleles, we generated transgenic Arabidopsis expressing a functional wild-type R, a non-functional r-1, or a dominant RD-2 allele. Expression levels of flavonoid/anthocyanin biosynthetic genes and anthocyanin production were highly increased in the transgenic plants expressing the dominant Ruby allele by its retrotransposon-mediated native promoter under cold treatment, suggesting that the retrotransposon may contain cis-regulatory elements that respond to cold temperature. Our results also support that the MYB TF encoded by Ruby could be a key component of regulatory complexes that control flavonoid/anthocyanin biosynthesis in citrus.

We investigated whether diclofenac could influence the development of antigen-presenting cells in an oxygenated cholesterol-rich environment by determining its effects on the 27-hydroxycholesterol (27OHChol)-induced differentiation of monocytic cells into mature dendritic cells (mDCs). Treatment of human THP-1 monocytic cells with diclofenac antagonized the effects of 27OHChol by attenuating dendrite formation and cell attachment and promoting endocytic function. Diclofenac inhibited the transcription and surface expression of the mDC markers of CD80, CD83, and CD88, and reduced the 27OHChol-induced elevation of surface levels of MHC class I and II molecules to the basal levels in a dose-dependent manner. It also reduced the expression of CD197, a molecule involved in DC homing and migration. These results indicate that diclofenac inhibits the differentiation of monocytic cells into mDCs, thereby potentially modulating adaptive immune responses in a milieu rich in cholesterol oxidation products.

27-Hydroxycholesterol induces differentiation of monocytic cells into mature dendritic cells, mDCs. In the current study we sought to determinen roles of the PI3K and the ERK pathways in the 27OHChol-induced differentiation. Up-regulation of mDC-specific markers like CD80, CD83 and CD88 induced by stimulation with 27OHChol was significantly reduced in the presence of LY294002, an inhibitor of PI3K, and U0126, an inhibitor of ERK. Surface expression of MHC class I and II molecules elevated by 27OHChol was decreased to basal levels in the presence of the inhibitors. Treatment with LY294002 or U0126 resulted in recovery of endocytic activity which was reduced by 27OHChol. CD197 expression and cell adherence enhanced by 27OHChol were attenuated in the presence of the inhibitors. Transcription and surface expression of CD molecules involved in atherosclerosis such as CD105, CD137 and CD166 were also significantly decreased by treatment with LY294002 and U0126. These results mean that the PI3K and the ERK signaling pathways are necessary for differentiation of monocytic cells into mDCs and involved in over-expression of atherosclerosis-associated molecules in response to 27OHChol.

The preponderance of temporomandibular joint (TMJ) degenerative disorders in women and their early onset during reproductive years have implicated female sex hormones, particularly 17-β estradiol (E2), in the pathogenesis of these disorders. Nevertheless, the mechanisms by which E2 contributes to TMJ degenerative disorders and the reasons for its targeted effects on the TMJ but not other joints remain poorly understood. Here, we developed an ovariectomized mouse model in which systemic E2 concentrations mimicked those in cycling women, and we determined the effect of E2 on the targeted turnover of TMJ fibrocartilage matrix via E2-induced matrix metalloproteinases MMP9 and MMP13. Infusion of E2 and progesterone (P4; hormone control) over 7 d resulted in 5- and 8-fold greater serum E2 and P4 levels relative to controls, respectively, achieving systemic hormone levels similar to high baseline levels in cycling women. Administration of E2 but not P4 caused a significant loss of TMJ collagen and glycosaminoglycans, which was accompanied by amplification of ERα and specific increases in MMP9 and MMP13 expression. This dose of E2 had no effect on knee meniscus fibrocartilage, demonstrating the specificity of the degradative effect of E2. Dose-response experiments showed a greater sensitivity and a higher peak induction of MMP9 and MMP13 in TMJ fibrocartilaginous cells than knee meniscus cells to E2, providing an explanation for the differential responses of these tissues to E2. Using MMP9- and MMP13-null mice, we observed no discernible effects of each proteinase individually to E2-mediated TMJ matrix loss but noted a significant compensatory reciprocal induction of each MMP by E2 in the absence of the other. The redundancy in E2’s induction of MMP9 and MMP13 suggests that the proteinases may together contribute to E2-mediated TMJ fibrocartilage loss. These results advance our understanding of E2-mediated upregulation of MMP9 and MMP13 on fibrocartilage matrix turnover targeted to the TMJ.

Many citrus cultivars have the polyembryony trait that develops many nucellar embryos alongside a single zygotic embryo in an individual seed by sporophytic apomixis. This unique botanical trait hinders citrus breeding by genetic hybridization and affects breeding efficiency and cost. Techniques to efficiently identify nucellar and zygotic individuals in citrus are still very limited. For a systematic and targeted citrus breeding program, we collected 101 citrus genetic resources and determined their embryo types, which revealed 22 monoembryo, 54 polyembryo, and 25 mixed types. We also developed 17 simple sequence repeat (SSR) markers showing polymorphism among the genetic resources from the public resources and our own comparative genome analysis. Seventeen SSR markers detected a total of 181 alleles, ranging from 5 to 16 alleles per locus. The average polymorphism information content value was 0.67, ranging from 0.43 to 0.84. Genetic cluster analysis based on similarity matrices of alleles revealed that several genetic resources of the genus Citrus were fragmented and/or scattered throughout the entire dendrogram, not forming unique groups, due to frequent natural or intended genetic crossings. Application of these polymorphic SSR markers to F1 individuals derived from several genetic crosses using polyembryonic citrus cultivars as a female parent revealed that the polyembryony trait decreased the breeding efficiency due to the poor occurrence rate of zygotic individuals. Therefore, our results suggest that identification of nucellar and zygotic embryo-derived F1 individuals using SSR markers as a genotyping technology may be a powerful tool for establishing a systematic molecular breeding program in citrus.