Lee, Sangbae;Lee, Yuno;Briggs, James M.;Lee, Keun Woo
Bulletin of the Korean Chemical Society
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제34권7호
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pp.1972-1984
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2013
Microtubules play an important role in intracellular transport, mobility, and particularly mitosis. Paclitaxel (Taxol$^{TM}$) and paclitaxel-like compounds have been shown to be anti-tumor agents useful for various human tumors. Paclitaxel-like compounds operate by stabilizing microtubules through interface binding at the interface between two ${\beta}$-tubulin monomers in adjacent protofilaments. In this paper we present the elucidation of the structural features of paclitaxel and paclitaxel-like compounds (e.g., epothilones) with microtubule stabilizing activities, and relate their activities to spatial and chemical features of the molecules. CATALYST program was used to generate three-dimensional quantitative structure activity relationships (3D-QSARs) resulting in 3D pharmacophore models of epothilone- and paclitaxel-derivatives. Pharmacophore models were generated from diverse conformers of these compounds resulting in a high correlation between experimental and predicted biological activities (r = 0.83 and 0.91 for epothilone and paclitaxel derivatives, respectively). On the basis of biological activities of the training sets, five- and four-feature pharmacophore hypotheses were generated in the epothilone and paclitaxel series. The validation of generated hypotheses was achieved by using twelve epothilones and ten paclitaxels, respectively, which are not in the training sets. The clustering (grouping) and merging techniques were used in order to supplement spatial restrictions of each of hypothesis and to develop more comprehensive models. This approach may be of use in developing novel inhibitor candidates as well as contributing a better understanding of structural characters of many compounds useful as anticancer agents targeting microtubules.
Investigations of the commercial aircraft impact effect on nuclear island infrastructures have been drawing extensive attention, and this paper aims to perform the safety assessment of Generation III nuclear power plant (NPP) buildings subjected to typical commercial aircrafts crash. At present Part I, finite element (FE) models establishment and validations for both the aircrafts and NPP buildings are performed. (i) Airbus A320 and A380 aircrafts are selected as the representative medium and large commercial aircrafts, and the corresponding fine FE models including the skin, beam, fuel and etc. are established. By comparing the numerically derived impact force time-histories with the existing published literatures, the rationality of aircrafts models is verified. (ii) Fine FE model of the Chinese Zhejiang Sanao NPP buildings is established, including the detailed structures and reinforcing arrangement of both the containment and auxiliary buildings. (iii) By numerically reproducing the existing 1/7.5 scaled aircraft model impact tests on steel plate reinforced concrete (SC) panels and assessing the impact process and velocity time-history of aircraft model, as well as the damage and the maximum deflection of SC panels, the applicability of the existing three concrete constitutive models (i.e., K&C, Winfrith and CSC) are evaluated and the superiority of Winfrith model for SC panels under deformable missile impact is verified. The present work can provide beneficial reference for the integral aircraft crash analyses and structural damage assessment in the following two parts of this paper.
The statistical characteristics of typhoon wind speed records tend to have a considerable time-varying trend; thus, the stationary wind model may not be appropriate to estimate the wind characteristics of typhoon events. Several nonstationary wind speed models have been proposed by pioneers to characterize wind characteristics more accurately, but comparative studies on the applicability of the different wind models are still lacking. In this study, three landfall typhoons, Ampil, Jongdari, and Rumbia, recorded by ultrasonic anemometers atop the Shanghai World Financial Center (SWFC), are used for the comparative analysis of stationary and nonstationary wind characteristics. The time-varying mean is extracted with the discrete wavelet transform (DWT) method, and the time-varying standard deviation is calculated by the autoregressive moving average generalized autoregressive conditional heteroscedasticity (ARMA-GARCH) model. After extracting the time-varying trend, the longitudinal wind characteristics, e.g., the probability distribution, power spectral density (PSD), turbulence integral scale, turbulence intensity, gust factor, and peak factor, are comparatively analyzed based on the stationary wind speed model, time-varying mean wind speed model and time-varying standard deviation wind speed model. The comparative analysis of the different wind models emphasizes the significance of the nonstationary considerations in typhoon events. The time-varying standard deviation model can better identify the similarities among the different typhoons and appropriately describe the nonstationary wind characteristics of the typhoons.
Macroscopic accident analyses have been conducted to incorporate transportation safety into long-term transportation planning. In macro-level accident prediction model, exposure variable(e.g. a settled population) have been used as fundamental explanatory variable under the concept that each trip will be subjected to a probable risk of accident. However, a settled population may be embedded error by exclusion of active population concept. The objective of this research study is to develop macro-level accident prediction model using floating population variable(concept of including a settled population and active population) collected from mobile phone data. The concept of accident prediction models is introduced utilizing exposure variable as explanatory variable in a generalized linear regression with assumption of a negative binomial error structure. The goodness of fit of model using floating population variable is compared with that of the each models using population and the number of household variables. Also, log transformation models are additionally developed to improve the goodness of fit. The results show that the log transformation model using floating population variable is useful for capturing the relationships between accident and exposure variable and generally perform better than the models using other existing exposure variables. The developed model using floating population variable can be used to guide transportation safety policy decision makers to allocate resources more efficiently for the regions(or zones) with higher risk and improve urban transportation safety in transportation planning step.
Objective : We have reviewed the potential cancer preventive and other relevant properties of Panax ginseng C. A. Meyer, which has been traditionally used as a natural tonic in oriental countries. Data identification and study selection: Publications on Panax ginseng and its relation to cancer were obtained from the Medline database (1983-2000) and by checking reference lists to find earlier reports. The reports cover experimental models and human studies on cancer-preventive activity, carcinogenicity and other beneficial or adverse effects. In addition, possible mechanisms of chemoprevention by ginseng were also considered. Results : Published results from a cohort and two case-control studies in Korea suggest that the intake of ginseng may reduce the risk of several types of cancer. When ginseng was tested in animal models, a reduction in cancer incidence and multiplicity at various sites was noted. Panax ginseng and its chemical constituents have been tested for their inhibiting effect on putative carcinogenesis mechanisms (e.g., cell proliferation and apoptosis, immunosurveillance, angiogenesis); in most experiments inhibitory effects were found. Conclusion : While Panax ginseng C. A. Meyer has shown cancer preventive effects both in experimental models and in epidemiological studies, the evidence is currently not conclusive as to its cancer-preventive activity in humans. The available evidence warrants further research into the possible role of ginseng in the prevention of human cancer and carcinogenesis.
In Korea, more than half of work-related fatalities have occurred on construction sites. To reduce such occupational accidents, safety inspection by government agencies is essential in construction sites that present a high risk of serious accidents. To address this issue, this study developed risk prediction models of serious accidents in construction sites using five machine learning methods: support vector machine, random forest, XGBoost, LightGBM, and AutoML. To this end, 15 proactive information (e.g., number of stories and period of construction) that are usually available prior to construction were considered and two over-sampling techniques (SMOTE and ADASYN) were used to address the problem of class-imbalanced data. The results showed that all machine learning methods achieved 0.876~0.941 in the F1-score with the adoption of over-sampling techniques. LightGBM with ADASYN yielded the best prediction performance in both the F1-score (0.941) and the area under the ROC curve (0.941). The prediction models revealed four major features: number of stories, period of construction, excavation depth, and height. The prediction models developed in this study can be useful both for government agencies in prioritizing construction sites for safety inspection and for construction companies in establishing pre-construction preventive measures.
Park, Sunghoon;Kim, Joo-Hee;Hwang, Yong Il;Jung, Ki-Suck;Jang, Young Sook;Jang, Seung Hun
Tuberculosis and Respiratory Diseases
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제76권3호
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pp.114-119
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2014
Background: Epigallocatechin-3-gallate (EGCG), a major biologically active component of green tea, has anti-cancer activity in human and animal models. We investigated the schedule-dependent effect of EGCG and paclitaxel on growth of NCI-H460 non-small cell lung cancer cells. Methods: To investigate the combined effect of EGCG (E) and paclitaxel (P), combination indices (CIs) were calculated, and cell cycle analysis was performed. For the effect on cell apoptosis, western blot analysis was also performed. Results: CI analysis demonstrated that both concurrent and sequential E ${\rightarrow}$ P treatments had antagonistic effects (CIs >1.0), but sequential P ${\rightarrow}$ E had synergistic effects (CIs <1.0), on the growth inhibition of NCI-H460 cells. In the cell cycle analysis, although paclitaxel induced $G_2/M$ cell cycle arrest and increased the sub-G1 fraction, concurrent EGCG and paclitaxel treatments did not have any additive or synergistic effects compared with the paclitaxel treatment alone. However, western blot analysis demonstrated that sequential P ${\rightarrow}$ E treatment decreased the expression of Bcl-2 and procaspase-3 and increased poly(ADP-ribose) polymerase (PARP) cleavage; while minimal effects were seen with concurrent or sequential E ${\rightarrow}$ P treatments. Conclusion: Concurrent or sequential E ${\rightarrow}$ P treatment had opposite effects to P ${\rightarrow}$ E treatment, where P ${\rightarrow}$ E treatment showed a synergistic effect on growth inhibition of NCI-H460 cells by inducing apoptosis. Thus, the efficacy of EGCG and paclitaxel combination treatment seems to be schedule-dependent.
Purpose: In the restaurant sector, it has been known that consumers' positive perception of brands influences their positive WOM intention, and information sources play an important role in increasing credibility by enhancing consumer awareness and developing differentiated brands. This study examines the effects of information sources (e.g., advertisement, WOM, SNS) on trust (cognitive and affective) and, WOM and eWOM intention in the restaurant context. In the model, cognitive and affective trust play mediating roles in the relationships between information sources (e.g., advertisement, WOM, SNS) WOM and eWOM intention. Research design, data, and methodology: Research models and hypotheses were developed according to the research direction. The survey questionnaire items were developed and used appropriately according to the contents of this paper based on prior studies. All constructs were measured with multiple items developed and validated in prior studies. A total of 502 responses were collected from an online survey. The research model was evaluated using SmartPLS 4.0. Frequency analysis was performed to understand the demographic characteristics of the survey respondents. The reliability, convergent validity, and discriminant validity were assessed using measurement model analysis. The proposed model was verified using the structural equation model. Results: Advertisement, WOM, and SNS information sources all had a positive effect on affective trust, whereas only WOM had a significant effect on cognitive trust. In addition, affective trust had a positive effect on cognitive trust and eWOM intention but did not affect WOM intention. Finally, cognitive trust was found to have a positive effect on both WOM intention and eWOM intention. Conclusions: This study redefines the concept of where restaurant service companies should focus when providing consumers with information about their products and services. As a result, the conceptual framework of positive word of mouth intention to increase new customer visits to the restaurant brand has been expanded. In addition, this study not only presents an information source management strategy for restaurant brands, but also presents practical implications for resource allocation guidelines for customer management in the restaurant sector.
Representative human models (RHMs), a group of digital human models which represent the people of the target population within a designated percentage (e.g., 95%), are used for ergonomic design and evaluation in virtual environments. The present study evaluated the grid approach, a RHM generation method, in terms of accommodation percentage. RHMs generated from the grid approach dramatically decreased the accommodation percentage of the target population as the number of anthropometric dimensions under consideration increased. For example, the accommodation percentages by RHMs generated by the grid approach were 95% for 3 key dimensions (selected among 10 anthropometric dimensions), 45% for 5 dimensions, and 10% for 10 dimensions. A standardized multiple regression analysis found that this decreasing accommodation percentage was caused by low correlations between key dimensions and other dimensions. The accommodation evaluation process used in the present study is applicable to evaluation of other RHM generation methods.
In robotics and other fields of engineering, techniques for artificial reality or virtual reality are focused on and studied extensively, e.g., virtual existence for tele-operator systems in robotics, and virtual reality of designed objects in architecture. In order to realize the system we should create physical stimulations according to internal models created by experiences in a human brain. The internal model does not have to have direct connections to the real world, however, the stimulation must be signals such that the internal model are retrieved in a human brain. In this paper we propose a technique for tele-virtual reality of dynamic mechanical models, which means that one dynamic mechanical model can be shared by peoples in distant places. Since a stability issue due to time delays arises in the system, we employed a scattering technique developed for a tele-operator system and a kind of passive adaptive controllers. Furthermore, restrictions due to a simple digital implementation of the scattering transformation are discussed and some conditions for stability are shown. The proposed method is applied to a remote tug of war system and the effectiveness is verified.
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