• Molecular & Cellular Toxicology
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• v.3 no.2
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• pp.137-144
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• 2007

The mechanism of cytotoxicity of doxifluridine, a prodrug fluorouracil (5-FU), has been ascribed to the misincorporation of fluoropyrimidine into RNA and DNA and to the inhibition of the nucleotide synthetic enzyme thymidylate synthase. Increased understanding of the mechanism of 5-FU has led to the development of strategies that increases its anticancer activity or predicts its sensitivity to patients. Using GeneChip?? Rhesus Macaque Genome arrays, we analyzed gene expression profiles of doxifluridine after two weeks repeated administration in cynomolgus monkey. Kegg pathway analysis suggested that cytoskeletal rearrangement and cell adhesion remodeling were commonly occurred in colon, jejunum, and liver. However, expression of genes encoding extracellular matrix was distinguished colon from others. In colon, COL6A2, COL18A1, ELN, and LAMA5 were over-expressed. In contrast, genes included in same category were down-regulated in jejunum and liver. Interestingly, MMP7 and TIMP1, the key enzymes responsible for ECM regulation, were overexpressed in colon. Several studies were reported that both gene reduced cell sensitivity to chemotherapy-induced apoptosis. Therefore, we suggest they have potential as target for modulation of 5-FU action. In addition, the expression of genes which have been previously known to involve in 5-FU pathway, were examined in three organs. Particularly, there were more remarkable changes in colon than in others. In colon, ECGF1, DYPD, TYMS, DHFR, FPGS, DUT, BCL2, BAX, and BAK1 except CAD were expressed in the direction that was good response to doxifluridine. These results may provide that colon is a prominent target of doxifluridine and transcriptional profiling is useful to find new targets affecting the response to the drug.

• Journal of Animal Science and Technology
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• v.63 no.4
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• pp.854-863
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• 2021

Weaning induces physiological changes in intestinal development that affect pigs' growth performance and susceptibility to disease. As a posttranscriptional regulator, microRNAs (miRNAs) regulate cellular homeostasis during intestinal development. We performed small RNA expression profiling in the small intestine of piglets before weaning (BW), 1 week after weaning (1W), and 2 weeks after weaning (2W) to identify weaning-associated differentially expressed miRNAs. We identified 38 differentially expressed miRNAs with varying expression levels among BW, 1W, and 2W. Then, we classified expression patterns of the identified miRNAs into four types. ssc-miR-196a and ssc-miR-451 represent pattern 1, which had an increased expression at 1W and a decreased expression at 2W. ssc-miR-499-5p represents pattern 2, which had an increased expression at 1W and a stable expression at 2W. ssc-miR-7135-3p and ssc-miR-144 represent pattern 3, which had a stable expression at 1W and a decreased expression at 2W. Eleven miRNAs (ssc-miR-542-3p, ssc-miR-214, ssc-miR-758, ssc-miR-4331, ssc-miR-105-1, ssc-miR-1285, ssc-miR-10a-5p, ssc-miR-4332, ssc-miR-503, ssc-miR-6782-3p, and ssc-miR-424-5p) represent pattern 4, which had a decreased expression at 1W and a stable expression at 2W. Moreover, we identified 133 candidate targets for miR-196a using a target prediction database. Gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses revealed that the target genes were associated with 19 biological processes, 4 cellular components, 8 molecular functions, and 7 KEGG pathways, including anterior/posterior pattern specification as well as the cancer, PI3K-Akt, MAPK, GnRH, and neurotrophin signaling pathways. These findings suggest that miRNAs regulate the development of the small intestine during the weaning process in piglets by anterior/posterior pattern specification as well as the cancer, PI3K-Akt, MAPK, GnRH, and neurotrophin signaling pathways.

• Journal of Animal Science and Technology
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• v.64 no.2
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• pp.312-329
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• 2022

Feed cost is the main factor affecting the economic benefits of pig industry. Improving the feed efficiency (FE) can reduce the feed cost and improve the economic benefits of pig breeding enterprises. Liver is a complex metabolic organ which affects the distribution of nutrients and regulates the efficiency of energy conversion from nutrients to muscle or fat, thereby affecting feed efficiency. MicroRNAs (miRNAs) are small non-coding RNAs that can regulate feed efficiency through the modulation of gene expression at the post-transcriptional level. In this study, we analyzed miRNA profiling of liver tissues in High-FE and Low-FE pigs for the purpose of identifying key miRNAs related to feed efficiency. A total 212~221 annotated porcine miRNAs and 136~281 novel miRNAs were identified in the pig liver. Among them, 188 annotated miRNAs were co-expressed in High-FE and Low-FE pigs. The 14 miRNAs were significantly differentially expressed (DE) in the livers of high-FE pigs and low-FE pigs, of which 5 were downregulated and 9 were upregulated. Kyoto Encyclopedia of Genes and Genomes analysis of liver DE miRNAs in high-FE pigs and low-FE pigs indicated that the target genes of DE miRNAs were significantly enriched in insulin signaling pathway, Gonadotropin-releasing hormone signaling pathway, and mammalian target of rapamycin signaling pathway. To verify the reliability of sequencing results, 5 DE miRNAs were randomly selected for quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The qRT-PCR results of miRNAs were confirmed to be consistent with sequencing data. DE miRNA data indicated that liver-specific miRNAs synergistically acted with mRNAs to improve feed efficiency. The liver miRNAs expression analysis revealed the metabolic pathways by which the liver miRNAs regulate pig feed efficiency.

• IEMEK Journal of Embedded Systems and Applications
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• v.18 no.3
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• pp.89-100
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• 2023

Recently, on-device artificial intelligence (AI) solutions using mobile devices and embedded edge devices have emerged in various fields, such as computer vision, to address network traffic burdens, low-energy operations, and security problems. Although vision transformer deep learning models have outperformed conventional convolutional neural network (CNN) models in computer vision, they require more computations and parameters than CNN models. Thus, they are not directly applicable to embedded edge devices with limited hardware resources. Many researchers have proposed various model compression methods or lightweight architectures for vision transformers; however, there are only a few studies evaluating the effects of model compression techniques of vision transformers on performance. Regarding this problem, this paper presents a performance evaluation of vision transformers on embedded platforms. We investigated the behaviors of three vision transformers: DeiT, LeViT, and MobileViT. Each model performance was evaluated by accuracy and inference time on edge devices using the ImageNet dataset. We assessed the effects of the quantization method applied to the models on latency enhancement and accuracy degradation by profiling the proportion of response time occupied by major operations. In addition, we evaluated the performance of each model on GPU and EdgeTPU-based edge devices. In our experimental results, LeViT showed the best performance in CPU-based edge devices, and DeiT-small showed the highest performance improvement in GPU-based edge devices. In addition, only MobileViT models showed performance improvement on EdgeTPU. Summarizing the analysis results through profiling, the degree of performance improvement of each vision transformer model was highly dependent on the proportion of parts that could be optimized in the target edge device. In summary, to apply vision transformers to on-device AI solutions, either proper operation composition and optimizations specific to target edge devices must be considered.

• Clinical Endoscopy
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• v.57 no.3
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• pp.384-392
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• 2024

Background/Aims: Endoscopic ultrasound-guided tissue acquisition (EUS-TA) is a standard diagnostic method for biliary tract cancer (BTC), and samples obtained in this manner may be used for comprehensive genomic profiling (CGP). This study evaluated the utility of EUS-TA for CGP in a clinical setting and determined the factors associated with the adequacy of CGP in patients with BTC. Methods: CGP was attempted for 105 samples from 94 patients with BTC at the Aichi Cancer Center, Japan, from October 2019 to April 2022. Results: Overall, 77.1% (81/105) of the samples were adequate for CGP. For 22-G or 19-G fine-needle biopsy (FNB), the sample adequacy was 85.7% (36/42), which was similar to that of surgical specimens (94%, p=0.45). Univariate analysis revealed that 22-G or larger FNB needle usage (86%, p=0.003), the target primary lesions (88%, p=0.015), a target size ≥30 mm (100%, p=0.0013), and number of punctures (90%, p=0.016) were significantly positively associated with CGP sample adequacy. Conclusions: EUS-TA is useful for CGP tissue sampling in patients with BTC. In particular, the use of 22-G or larger FNB needles may allow for specimen adequacy comparable to that of surgical specimens.

• Journal of Microbiology and Biotechnology
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• v.25 no.2
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• pp.217-226
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• 2015

Metabolite profiles of seven commercial vinegars and two traditional vinegars were performed by gas chromatography time-of-flight mass spectrometry with multivariate statistical analysis. During alcohol fermentation, yeast, nuruk, and koji were used as sugars for nutrients and as fermentation substrates. Commercial and traditional vinegars were significantly separated in the principal component analysis and orthogonal partial least square discriminant analysis. Six sugars and sugar alcohols, three organic acids, and two other components were selected as different metabolites. Target analysis by ultra-performance liquid chromatography quadruple-time-of-flight mass spectrometry and liquid chromatography-ion trap-mass spectrometry/mass spectrometry were used to detect several metabolites having antioxidant activity, such as cyanidin-3-xylosylrutinoside, cyanidin-3-rutinoside, and quercetin, which were mainly detected in Rural Korean Black raspberry vinegar (RKB). These metabolites contributed to the highest antioxidant activity measured in RKB among the nine vinegars. This study revealed that MS-based metabolite profiling was useful in helping to understand the metabolite differences between commercial and traditional vinegars and to evaluate the association between active compounds of vinegar and antioxidant activity.

• Molecular & Cellular Toxicology
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• v.5 no.1
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• pp.67-74
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• 2009

Exposures to environmental chemicals that mimic endogenous hormones are proposed for a number of adverse health effects, including infertility, abnormal prenatal and childhood development and above all cancers. In addition, recently miRNA (micro RNA) has been recognized to play an important role in various diseases and in cellular and molecular responses to toxicants. In this study, endocrine disrupting environmental toxicant, nonylphenol (NP) was treated to MCF-7 (Human breast cancer cell) and HepG2 (Human hepatocellular liver carcinoma) cell line at 3 hrs and 48 hrs time point and miRNA analysis using $mirVana^{TM}$ miRNA bioarray was performed and compared with total mRNA microarray data for the same cell line and treatment. Robust data quality was achieved through the use of dye-swap. Analysis of microarray data identifies a total of 20 and 11 miRNA expressions at 3 hrs and 48 hrs exposure to NP in MCF-7 cell line and a total of 14 and 47 miRNA expression at 3 hrs and 48 hrs exposure respectively to NP in HepG2 cell line. Expression profiling of the selected miRNA (let-7c, miR-16, miR-195, miR-200b, miR200c, miR-205, and miR-589) reveals changes in the expression of target genes related to metabolism, immune response, apoptosis, and cell differentiation. The present study can be informative and helpful to understand the role of miRNA in molecular mechanism of chemical toxicity and their influence on hormone dependent disease. Also this study may prove to be a valuable tool for screening potential estrogen mimicking pollutants in the environment.

• Journal of Korean Ophthalmic Optics Society
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• v.4 no.1
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• pp.21-25
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• 1999

The TiN, thin films were prepared on glass substrate by RF(radio-frequency) magnetron sputtering apparatus from a Ti target in a gaseous mixture of argon and nitrogen. In deposition, a RF power supply was used as a power source with a constant power of 240W, and the substrate was heated to $200^{\circ}C$. The films were obtained at nitogen flow rates in the range 3-9 sccm with a constant argon flow rate of 20 secm. For the films obtained, the sheet resistance and the chemical binding energy of the films was observed by four-point-probe method and x-ray photoelectron spectroscopy(XPS) depth profiling respectively. In addition, we investigated the relationship between the surface resistance and the chemical nature of the films.

• BMB Reports
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• v.46 no.11
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• pp.539-543
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• 2013

There is a correlation between obesity and the amount of brown adipose tissue; however, the molecular mechanism of brown adipogenic differentiation has not been as extensively studied. In this study, we performed a protein tyrosine phosphatase (PTP) profiling analysis during the brown adipogenic differentiation of mouse primary brown preadipocytes. Several PTPs, including PTPRF, PTPRZ, and DUSP12 showing differential expression patterns were identified. In the case of DUSP12, the expression level is dramatically downregulated during brown adipogenesis. The ectopic expression of DUSP12 using a retroviral expression system induces the suppression of adipogenic differentiation, whereas a catalytic inactive DUSP12 mutant showed no effect on differentiation. These results suggest that DUSP12 is involved in brown adipogenic differentiation and may be used as a target protein for the treatment or prevention of obesity by the regulation of brown adipogenic differentiation.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.6 no.1
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• pp.40-51
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• 2006

Purpose: A personal computer-based system was developed for automated metabolic profiling of organic aciduria and aminoacidopathy by gas chromatography-mass spectrometry and data interpretation for the diagnosis of metabolic disorders Methods: For automatic data profiling and interpretation, we compiled retention time, two target ions and their intensity ratio for 77 organic acids and 13 amino acids metabolites. Metabolites above the cut-off values were flagged as abnormal compounds. The data interpretation was a based on combination of flagged metabolites. Diagnostic or index metabolites were categorized into three groups, "and", "or" and "NO" compiled for each disorder to improve the specificity of the diagnosis. Groups "and" and "or" comprised essential and optional compounds, respectively, to reach a specific diagnosis. Group "NO" comprised metabolites that must be absent to make a definite diagnosis. We tested this system by analyzing patients with confirmed Propionic aciduria and others. Results: In all cases, the diagnostic metabolites were identified and correct diagnosis was founded to be made among the possible disease suggested by the system. Conclusion: The study showed that the developed method could be the method of choices in rapid, sensitive and simultaneous screening for organic aciduria and amino acidopathy with this simplified automated system.