Abstract Drug repositioning aims to identify new therapeutic indications for approved medications. Recently, the importance of computational drug repositioning has been highlighted because it can reduce the costs, development time, and risks compared to traditional drug discovery. Most approaches in this area use networks for systematic analysis. Inferring drug-disease associations is then defined as a link prediction problem in a heterogeneous network composed of drugs and diseases. In this article, we present a novel method of computational drug repositioning, named drug repositioning with attention walking (DRAW). DRAW proceeds as follows: first, a subgraph enclosing the target link for prediction is extracted. Second, a graph convolutional network captures the structural features of the labeled nodes in the subgraph. Third, the transition probabilities are computed using attention mechanisms and converted into random walk profiles. Finally, a multi-layer perceptron takes random walk profiles and predicts whether a target link exists. As an experiment, we constructed two heterogeneous networks with drug-drug similarities based on chemical structures and anatomical therapeutic chemical classification (ATC) codes. Using 10-fold cross-validation, DRAW achieved an area under the receiver operating characteristic (ROC) curve of 0.903 and outperformed state-of-the-art methods. Moreover, we demonstrated the results of case studies for selected drugs and diseases to further confirm the capability of DRAW to predict drug-disease associations.
We previously reported that silk peptide (SP) treatment led to increased resting fat oxidation in exercised mice. However, it was not known whether SP treatment could effectively increase exercise capacity. Accordingly, this study aimed to examine whether SP treatment affected energy metabolism during exercise in addition to exercise performance.We randomized 36 7-week-old male ICR mice into 2 groups: the control (n = 18) and SP (n = 18) groups. All mice were trained by treadmill running 5 times per week for 2 weeks. SP was dissolved in distilled water and daily 800-mg/kg body weight doses before the running exercise were oral administered intraperitoneally to the SP group for 2 weeks. [Formula: see text] was measured before and after the 2 weeks training period. We also assessed energy metabolism during exercise for 1 h after the 2 week training period. In addition to blood samples, liver glycogen and gastrocnemius-white and gastrocnemius-red muscle was obtained at the following 3 time points: at rest, immediately after exercise, and 1-hour post exercise.The [Formula: see text] max after 2 weeks of training was significantly increased (8%) in the SP group compared to the baseline; a similar result was not observed in the CON group. The sum of fat oxidation during a 1-h period tended to be 13% higher in the SP group than in the CON group (P < 0.077). In particular, the sum of fat oxidation was significantly higher in the SP group during the initial 20-min phase than that in the CON group (P < 0.05). The glycogen concentration in the white gastrocnemius muscle did not differ between the groups either rest or after 1 h of exercise but was significantly higher in the SP group than in the CON group during the recovery period (1 h post-exercise completion).These results suggest that SP treatment can improve the exercise performance. Therefore, SP is considered to confer beneficial effects upon athletes, in whom exercise abilities are required.
A 1.2 V, 3.0 Gb/s/pin 16Tb NAND flash memory package with proposed 4 th generation F-chip is presented. It is implemented with self-training techniques such as hybrid delay locked loop (DLL) and 3-step duty cycle correction (DCC) to overcome the speed bottlenecks in F-chip to NAND interface. Also, its multi-termination feature improves power efficiency by providing the use of different terminations on its interfaces. This work achieves an I/O speed of 3.0 Gb/s and power consumption of 58mW which are an improvement of 66% and 23.3%, respectively, in comparison with 3 rd generation F-chip.
Yoon, J.-S.; Park, J-H.; Cho, Y.K.; Ha, T., and Lee, J.H., 2019. Experiments on efficiency review of new-type screens for waste treatment in the drainage canal. In: Lee, J.L.; Yoon, J.-S.; Cho, W.C.; Muin, M., and Lee, J. (eds.), The 3rd International Water Safety Symposium. Journal of Coastal Research, Special Issue No. 91, pp. 266-270. Coconut Creek (Florida), ISSN 0749-0208.Drainage canals installed for irrigation in farms are helplessly exposed to reckless garbages and municipal wastes. In addition, according to “Design Standards for Agricultural Drainage (2012)” of the Korean Ministry of Agriculture, Food and Rural Affairs, drainage canals with inlet flow below 5 m3/sec cannot use dust collectors, causing issues related to treatment of municipal wastes that accumulate in drainages. This study proposed a method of collecting municipal wastes by installing a separate dust collecting canal and screen in drainage canals as an alternative solution to these issues, and their efficiency was analyzed by a hydraulic model test. The hydraulic model test analyzed hydraulic characteristics according to different shapes (screen installation angle, screen blade angle) of screen I in the main drainage canal and the clogging of screen II in the dust collecting canal. The effect of collecting municipal wastes entering into the dust collecting canal was reviewed by applying the LS-PIV (Large Scale Particle Image Velocimetry) technique. Result of the hydraulic model test, highest efficiency was shown when length of screen I became longest with installation angle of 15° and blade angle of 30°. The concerned back-water phenomenon did not occur.
Here, we proposed an enzyme-linked oligonucleotide assay (ELONA) to quantitatively detect periostin using periostin-specific two ssDNA aptamers in a sandwich manner. Patients with T H 2-high asthma have higher periostin levels in their blood. The two aptamers (PL2 trim and PL5 trim ) developed for the first time in this study showed specific binding affinity (PL2 trim K d = 10.76 nM, PL5 trim K d =36.97 nM) and a dual binding property that did not interfere with each other for periostin. Indeed, the sandwich ELONA using the dual binding property showed a meaningful detection of periostin, and showed the best detection performance when the PL2 trim and PL5 trim were used as capture and detection aptamer, respectively. In addition, the sensitivity of the sandwich assay was significantly increased by introducing streptavidin-poly horseradish peroxidase (SA-poly HRP). The established assay system was able to detect periostin within 3 hours and achieved low detection limits of 0.32 nM and 5.3 nM in buffer and serum spike conditions, respectively. Moreover, the aptasensor detected only periostin by distinguishing it from other blood proteins in buffer. Therefore, the sandwich ELONA could provide cost-effectiveness, high sensitivity, and superior specificity for periostin, which proves a possible use in discriminating T H 2-high asthmatics with high periostin levels.
The antibacterial activities of methanol extracts of 19 commercial herbal medicines were measured against the fish pathogens Vibrio ichthyoenteri and Streptococcus iniae, which cause several fish diseases. Rhus javanica showed the strongest antibacterial activity against V. ichthyoenteri and S. iniae. The methanol extract of R. javanica was extracted further using several organic solvents with different polarities. The extract from the ethyl acetate fraction showed strong activity against both fish pathogens. The minimum inhibitory concentration (MIC) of the R. javanica extract was $32{\mu}g/mL$ for V. ichthyoenteri and $128{\mu}g/mL$ for S. iniae. Further purification and isolation of the active compound (s) responsible for these activities and further study of the synergistic effect using combinations of antibiotics against pathogenic bacteria are needed.
(1) The purpose of this study was to investigate the effect of whey protein supplementation under dietary control on improvements in muscle mass and function following resistance exercise training. (2) Thirty-two men were randomly assigned to a whey protein supplementation group taking whey protein isolate (PSG, n = 17) and a placebo group (CON, n = 15). Participants were provided with three meals per day corresponding to the estimated individual daily energy intake. The supervised resistance exercise program was conducted 60 min per day, six days per week, for four weeks. (3) Post-intervention, there was a significant interaction between groups in terms of muscle mass increase (p = 0.033, η2 = 0.14), with a greater increase in the PSG. There were also significant interactions between the groups and increases in peak torque of the dominant knee flexors (p = 0.048, η2 = 0.12), dominant shoulder extensors, and non-dominant shoulder extensors (p = 0.028, η2 = 0.15; p = 0.015, η2 = 0.18), and the total work of the dominant knee and shoulder extensors (p = 0.012, η2 = 0.19; p = 0.013, η2 = 0.19), with greater increases in the PSG. (4) These results suggest that whey protein supplementation enhances resistance exercise-induced increase in muscle mass and overall muscular strength and endurance, independent of dietary influence.
Background: Leprosy is a chronic infectious disease caused by Mycobacterium leprae and the treatment of choice is ofloxacin (OFX). Specific amino acid substitutions in DNA gyrase of M. leprae have been reported leading to resistance against the drug. In our previous study, WQ-3810, a fluoroquinolone with a new R1 group (6-amino-3,5-difluoropyridin-2-yl) was shown to have a strong inhibitory activity on OFX-resistant DNA gyrases of M. leprae, and the structural characteristics of its R1 group was predicted to enhance the inhibitory activity. Methodology/Principal Finding: To further understand the contribution of the R1 group, WQ-3334 with the same R1 group as WQ-3810, WQ-4064, and WQ-4065, but with slightly modified R1 group, were assessed on their activities against recombinant DNA gyrase of M. leprae. An in silico study was conducted to understand the molecular interactions between DNA gyrase and WQ compounds. WQ-3334 and WQ-3810 were shown to have greater inhibitory activity against M. leprae DNA gyrase than others. Furthermore, analysis using quinolone-resistant M. leprae DNA gyrases showed that WQ-3334 had greater inhibitory activity than WQ-3810. The R8 group was shown to be a factor for the linkage of the R1 groups with GyrB by an in silico study. Conclusions/Significance: The inhibitory effect of WQ compounds that have a new R1 group against M. leprae DNA gyrase can be enhanced by improving the binding affinity with different R8 group molecules. The information obtained by this work could be applied to design new fluoroquinolones effective for quinolone-resistant M. leprae and other bacterial pathogens.
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