• Genomics & Informatics
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• v.10 no.1
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• pp.33-39
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• 2012

High-throughput genomic technologies (HGTs), including next-generation DNA sequencing (NGS), microarray, and serial analysis of gene expression (SAGE), have become effective experimental tools for cancer genomics to identify cancer-associated somatic genomic alterations and genes. The main hurdle in cancer genomics is to identify the real causative mutations or genes out of many candidates from an HGT-based cancer genomic analysis. One useful approach is to refer to known cancer genes and associated information. The list of known cancer genes can be used to determine candidates of cancer driver mutations, while cancer gene-related information, including gene expression, protein-protein interaction, and pathways, can be useful for scoring novel candidates. Some cancer gene or mutation databases exist for this purpose, but few specialized tools exist for an automated analysis of a long gene list from an HGT-based cancer genomic analysis. This report presents a new web-accessible bioinformatic tool, called CaGe, a cancer genome annotation system for the assessment of candidates of cancer genes from HGT-based cancer genomics. The tool provides users with information on cancer-related genes, mutations, pathways, and associated annotations through annotation and browsing functions. With this tool, researchers can classify their candidate genes from cancer genome studies into either previously reported or novel categories of cancer genes and gain insight into underlying carcinogenic mechanisms through a pathway analysis. We show the usefulness of CaGe by assessing its performance in annotating somatic mutations from a published small cell lung cancer study.

• Asian-Australasian Journal of Animal Sciences
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• v.24 no.7
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• pp.1001-1006
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• 2011

To determine the efficiency of copper (Cu) supplementation, a feeding experiment was carried out with 240 day old broiler chicks (vencobb-100). Birds were divided into four dietary treatments: i) C - no additives, ii) $T_1$-75 mg inclusion of Cu/kg diet, iii) $T_2$-150 mg inclusion of Cu/kg diet, iv) $T_3$-250 mg inclusion of Cu/kg diet. The present study was carried out in the Department of Animal Physiology, West Bengal University of Animal and Fishery Sciences, Kolkata, India for a period of 42 days (6 weeks). Growth performance was measured in terms of live weight gain, cumulative feed intake and feed conversion ratio at the end of $21^{st}$ and $42^{nd}$ day of the experiment and the result was found to be encouraging for commercial enterprises when the chickens were fed at 150 mg Cu/kg ($T_2$) of their diet. Excess dietary copper more than 150 mg/kg reduced the haemoglobin (Hb) concentration in blood and resulted in the accumulation of copper in the liver with decreased blood Hb concentration and packed cell volumes (PCV). Copper supplementation increased the total erythrocyte count (TEC) as copper is involved in erythropoiesis. But, from the result it is indicated that the dietary copper concentration could not alter the total leukocyte count (TLC). In case of different leucocytes count (DLC), there were no significant differences observed among the different treated groups. Statistical analysis showed significant (p<0.01) difference in plasma concentration of copper, zinc, ferrous and cholesterol among the different copper treated groups. The result indicates that supplementation of copper is an effective way of improving the production performance and haematological parameters in broiler chicken.

• Microbiology and Biotechnology Letters
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• v.21 no.4
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• pp.354-365
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• 1993

A novel control method with automatic tuning of PID controller parameters has been developed for efficient regulation of dissolved oxygen concentration in fed-batch fermentations of Escherichia coli. Agitation speed and oxygen partial pressure in the inlet gas stream were chosen to be the manipulated variables. A heuristic reasoning allowed improved tuning decisions from the supervision of control performance indices and it coule obviate the needs for process assumptions or disturbance patterns. The control input consisted of feedback and feedforword parts. The feedback part was determined by PID control and the feedforward part is determined from the feed rate. The proportional gain was updated on-line by a set of heuristics rules based on the supervision of three performance indices. These indices were output error covariance, the average value of output error, and input covariance, which were calculated on-line using a moving window. The integral and derivative time constants were determined from the period of output response. The specific growth rate was maintained at a low level to avoid acetic acid accumulation and thus to achieve a high cell density. The specific growthe rate was estimated from the carbon dioxide evolution rate. In fed-batch fermentation, the simutaneous control of dissolved oxygen concentration (at 0.2; fraction of saturated value) and specific growth rate (at 0.25$hr^{-1}$) was satisfactory for the entire culture period in spite of the changes in the feed rate and the switching of control input.

• Biomolecules & Therapeutics
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• v.5 no.2
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• pp.133-149
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• 1997

4-week repeated dose toxicity of DA-5018, a new capsaicin analogue analgesic agent, was examined in 5D rats at dosage levels of 0,0.4,2, 10 and 50 mg/kg/day. DA-5018 was administered orally to 17 males and 17 females per group at doses of 0, 10 and 50 mg/kg and to 12 males and 12 females per group at doses of 0.4 and 2 mg/kg. After the administration period, 5 males and 5 females at the 0, 10 and 50 mg/kg were placed on withdrawal for 2 weeks. Treatment-related clinical signs were observed at 10 and 50 mg/kg. Clinical signs observed immediately after the administration of DA-5018 were grooming, sedation or depression, lacrimation, atacia, reddening of extremities and ears, ventral or lateral recumvincy, respiratory distress, cyanosis and convulsion. Delayed-type clinical signs including focal scabbing and depilation around nose were also observed 1 or 2 weeks after the start of administration of DA-5018. Only at the 50 mg/kg group, corneal opacities, reduced body weight gain (male) and death (male 6/17, female 3/17) were noted. In blood biochemical analysis, serum levels of glucose and triglyceride decreased at 10 and 50 mg/kg. In hematological examination, there were increases in the number of red blood cell, hemoglobin content and percent of hematocrit at 10 and 50 mg/kg. Pulmonary enlargement and hemorrhagic spot, focal scabbing and depilation around nose and corneal opacities were seen at the necropsy of the animals died during the dosing of DA-5018 50 mg/kg. Focal scabbing and depilation around nose were observed in the animals terminally necropsied at doses of 10 and 50 mg/kg. Histopathological examination revealed pulmonary hemorrhage, focal necrosis in the scabbed area, corneal necrosis, fibrosis and neovasculization in the stroma. At 0.4 and 2 mg/kg, there were no significant toxic changes attributable to the administration of DA-5018. In conclusion, target organs following to 4-week repeated dose of DA-5018 in the rat were determined to be lung, skin and eyes. Definite toxic dose and no-observed-adverse-effect-level (NOAEL) were estimated to be 50 and 2 mg/kg/day, respectively.

• Biomolecules & Therapeutics
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• v.26 no.6
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• pp.599-607
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• 2018

Fasiglifam (TAK-875) a G-protein coupled receptor 40 (GPR40) agonist, significantly improves hyperglycemia without hypoglycemia and weight gain, the major side effects of conventional anti-diabetics. Unfortunately, during multi-center Phase 3 clinical trials, unexpected liver toxicity resulted in premature termination of its development. Here, we investigated whether TAK-875 directly inflicts toxicity on hepatocytes and explored its underlying mechanism of toxicity. TAK-875 decreased viability of 2D and 3D cultures of HepG2, a human hepatocarcinoma cell line, in concentration-(>$50{\mu}M$) and time-dependent manners, both of which corresponded with ROS generation. An antioxidant, N-acetylcysteine, attenuated TAK-875-mediated hepatotoxicity, which confirmed the role of ROS generation. Of note, knockdown of GPR40 using siRNA abolished the hepatotoxicity of TAK-875 and attenuated ROS generation. In contrast, TAK-875 induced no cytotoxicity in fibroblasts up to $500{\mu}M$. Supporting the hepatotoxic potential of TAK-875, exposure to TAK-875 resulted in increased mortality of zebrafish larvae at$25{\mu}M$. Histopathological examination of zebrafish exposed to TAK-875 revealed severe hepatotoxicity as manifested by degenerated hypertrophic hepatocytes with cytoplasmic vacuolation and acentric nuclei, confirming that TAK-875 may induce direct hepatotoxicity and that ROS generation may be involved in a GPR40-dependent manner.

• Journal of Advanced Marine Engineering and Technology
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• v.39 no.3
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• pp.280-285
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• 2015

We consider a linear transceiver design method for multi-user multiple-input multiple-output (MIMO) downlink channels where a base station (BS) equipped with a finitely large number of antennas. Although a matched-filter precoder is a capacity-achieving method in massive MIMO downlink systems, it cannot guarantee to achieve the multi-user MIMO capacity in a finitely large number of antennas due to inter-user interferences. In this paper, we propose a two-stage precoder design method that maximizes the sum-rate of cell-edge users when the BS equipped with a finitely large number of antennas. At the first stage, a matched-filter precoder is adopted to exploit both beamforming gain and the reduction of the dimension of effective channels. Then, we derive the second stage precoder that maximizes the sum-rate by minimizing the weighted mean square error (WMSE). From simulation and analysis, we verify the effectiveness of the proposed method.

• Journal of Korea Society of Industrial Information Systems
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• v.17 no.7
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• pp.9-16
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• 2012

In order to extend cell coverage and to cope with shadow areas, a relay-assisted wireless communications system has been widely studied. In this paper, we propose new equalization method for single carrier (SC) frequency domain equalizer (FDE) in amplify-and-forward (AF) relaying multi-path networks to improve the performance at shadow areas. The performance of SC-FDE system in 3-slot based multi-path networks can be improved considerably with the diversity gain which we obtain by equalizing the combined signal from relays by means of the minimum mean square error (MMSE) criteria. We find the weighting coefficients of maximum ratio combining (MRC) and the tap coefficients of MMSE equalizer for SC-FDE in AF relaying multi-path networks. Simulation results show that the proposed system considerably outperforms the conventional SC-FDE system.

• Journal of Animal Science and Technology
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• v.57 no.1
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• pp.4.1-4.5
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• 2015

The study was performed to investigate the effect of dietary supplementation of a lipid-encapsulated Zinc oxide on growth parameters and intestinal mucosal morphology piglets born to Duroc-sired Landrace ${\times}$ Yorkshire dams. Twenty-four 30-day-old piglets weaned at 25 days of age were orally challenged with $5{\times}10^8$ colony forming units of enterotoxigenic Escherichia coli (ETEC) K88 and fed one of the four diets for 7 days: (i) a nursery basal diet containing 100-ppm ZnO (referred to as BASAL), (ii) BASAL supplemented with 120-ppm apramycin (referred to as ANTIBIO), (iii) BASAL with 2,400-ppm ZnO (referred to as HIGH), and BASAL containing 100-ppm lipid-encapsulated ZnO (referred to as LE). All piglets were killed at the end of the experiment for histological examination on the intestine. The results showed that the average daily gain (ADG), the villus height: crypt depth (CD) ratio in the ileum, and the goblet cell density of the villus and crypt in the duodenum, jejunum, and colon were greater in the LE-fed group that those of the BASAL (p < 0.05). Fecal consistency score (FCS) and the CD ratio in the ileum were less in the LE-fed group, compared to the BASAL-fed one (p < 0.05). The effects observed in the LE-fed group were almost equal to those of the HIGH-fed group as well as even superior to those of the ANTIBIO-fed group. Taken together, our results imply that dietary supplementation of 100-ppm lipid-encapsulated ZnO is as effective as that of 2,400-ppm ZnO for promoting growth diarrhea and intestinal morphology caused by ETEC infection.

• Asian-Australasian Journal of Animal Sciences
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• v.20 no.10
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• pp.1473-1477
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• 2007

Four-and-a-half LIM-only protein 3 (FHL3) is a member of the LIM protein superfamily and can participate in mediating protein-protein interaction by binding one another through their LIM domains. In this study, the 5'- and 3'- cDNA ends were characterized by RACE (Rapid Amplification of the cDNA Ends) methodology in combination with in silico cloning based on the partial cDNA sequence obtained. Bioinformatics analysis showed FHL3 protein contained four LIM domains and four LIM zinc-binding domains. In silico mapping assigned this gene to the gene cluster MTF1-INPP5B-SF3A3-FHL3-CGI-94 on pig chromosome 6 where several QTL affecting intramuscular fat and eye muscle area had previously been identified. Transcription of the FHL3 gene was detected in spleen, liver, kidney, small intestine, skeletal muscle, fat and stomach, with the greatest expression in skeletal muscle. The A/G polymorphism in exon II was significantly associated with birth weight, average daily gain before weaning, drip loss rate, water holding capacity and intramuscular fat in a Landrace-derived pig population. Together, the present study provided the useful information for further studies to determine the roles of FHL3 gene in the regulation of skeletal muscle cell growth and differentiation in pigs.

• Journal of Microbiology and Biotechnology
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• v.27 no.3
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• pp.500-506
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• 2017

To investigate the potential applications of bacterial heme, aminolevulinic acid synthase (HemA) was expressed in a Corynebacterium glutamicum HA strain that had been adaptively evolved against oxidative stress. The red pigment from the constructed strain was extracted and it exhibited the typical heme absorbance at 408 nm from the spectrum. To investigate the potential of this strain as an iron additive for swine, a prototype feed additive was manufactured in pilot scale by culturing the strain in a 5 ton fermenter followed by spray-drying the biomass with flour as an excipient (biomass: flour = 1:10 (w/w)). The 10% prototype additive along with regular feed was supplied to a pig, resulting in a 1.1 kg greater increase in weight gain with no diarrhea in 3 weeks as compared with that in a control pig that was fed an additive containing only flour. To verify if C. glutamicum-synthesized heme is a potential electron carrier, lactic acid bacteria were cultured under aerobic conditions with the extracted heme. The biomasses of the aerobically grown Lactococcus lactis, Lactobacillus rhamosus, and Lactobacillus casei were 97%, 15%, and 4% greater, respectively, than those under fermentative growth conditions. As a potential preservative, cultures of the four strains of lactic acid bacteria were stored at $4^{\circ}C$ with the extracted heme and living lactic acid bacterial cells were counted. There were more L. lactis and L. plantarum live cells when stored with heme, whereas L. rhamosus and L. casei showed no significant differences in live-cell numbers. The potential uses of the heme from C. glutamicum are further discussed.