Pharmacophore Modeling, Virtual Screening and Molecular Docking Studies for Identification of New Inverse Agonists of Human Histamine H1 Receptor
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- Bulletin of the Korean Chemical Society
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- v.31 no.1
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- pp.52-58
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- 2010
Human histamine H1 receptor (HHR1) is a G protein-coupled receptor and a primary target for antiallergic therapy. Here, the ligand-based three-dimensional pharmacophore models were built from a set of known HHR1 inverse agonists using HypoGen module of CATALYST software. All ten generated pharmacophore models consist of five essential features: hydrogen bond acceptor, ring aromatic, positive ionizable and two hydrophobic functions. Best model had a correlation coefficient of 0.854 for training set compounds and it was validated with an external test set with a high correlation value of 0.925. Using this model Maybridge database containing 60,000 compounds was screened for potential leads. A rigorous screening for drug-like compounds unveiled RH01692 and SPB00834, two novel molecules for HHR1 with good CATALYST fit and estimated activity values. The new lead molecules were docked into the active site of constructed HHR1 homology model based on recently crystallized squid rhodopsin as template. Both the hit compounds were found to have critical interactions with Glu177, Phe432 and other important amino acids. The interpretations of this study may effectively be deployed in designing of novel HHR1 inverse agonists.
Various LIDs with natural water circulation function are applied to reduce urban environmental problems and environmental impact of development projects. However, excessive Infiltration and evaporation of LID facilities dry the LID internal soil, thus reducing plant and microbial activity and reducing environmental re duction ability. The purpose of this study was to develop a real-time measurement system with complex sensors to derive the management plan of LID facilities. The test of measurable sensors and Internet of Things (IoT) application was conducted in artificial wetlands shaped in acrylic boxes. The applied sensors were intended to be built at a low cost considering the distributed LID and were based on Arduino and Raspberry Pi, which are relatively inexpensive and commercialized. In addition, the goal was to develop complex sensor measurements to analyze the current state o f LID facilities and the effects of maintenance and abnormal weather conditions. Sensors are required to measure wind direction, wind speed, rainfall, carbon dioxide, Micro-dust, temperature and humidity, acidity, and location information in real time. Data collection devices, storage server programs, and operation programs for PC and mobile devices were developed to collect, transmit and check the results of measured data from applied sensors. The measurements obtained through each sensor are passed through the Wifi module to the management server and stored on the database server in real time. Analysis of the four-month measurement result values conducted in this study confirmed the stability and applicability of ICT technology application to LID facilities. Real-time measured values are found to be able to utilize big data to evaluate the functions of LID facilities and derive maintenance measures.
The KMA has cooperated with the Oklahoma University in USA to develop a Polarimetric Radar Data (PRD) simulator to improve the microphysical processes in Korea Local Analysis and Prediction System (KLAPS), which is critical for the utilization of PRD into Numerical Weather Prediction (NWP) field. The simulator is like a tool to convert NWP data into PRD, so it enables us to compare NWP data with PRD directly. The simulator can simulate polarimetric radar variables such as reflectivity (Z), differential reflectivity (
Silent information regulator 2 (Sir2) or sirtuins are NAD(+)-dependent deacetylases, which hydrolyze the acetyllysine residues. In mammals, sirtuins are classified into seven different classes (SIRT1-7). SIRT1 was reported to be involved in age related disorders like obesity, metabolic syndrome, type II diabetes mellitus and Parkinson’s disease. Activation of SIRT1 is one of the promising approaches to treat these age related diseases. In this study, we have used HipHop module of CATALYST to identify a series of pharmacophore models to screen SIRT1 enhancing molecules. Three molecules from Sirtris Pharmaceuticals were selected as training set and 607 sirtuin activator molecules were used as test set. Five different hypotheses were developed and then validated using the training set and the test set. The results showed that the best pharmacophore model has four features, ring aromatic, positive ionization and two hydrogen-bond acceptors. The best hypothesis from our study, Hypo2, screened high number of active molecules from the test set. Thus, we suggest that this four feature pharmacophore model could be helpful to screen novel SIRT1 activator molecules. Hypo2-virtual screening against Maybridge database reveals seven molecules, which contains all the critical features. Moreover, two new scaffolds were identified from this study. These scaffolds may be a potent lead for the SIRT1 activation.
Many researchers have studied flash memory in order to replace hard disk storages. Many FTL algorithms have been proposed to overcome physical constraints of flash memory such as erase-before-write, wear leveling, and poor write performance. Therefore, these constraints should be considered for testing FTL algorithms and the performance evaluation of flash memory. As doing the experiments, we suffer from several problems with costs and settings in experimental configuration. When we, for example, replay the traces of Oracle to evaluate the I/O performance with flash memory, it is hard to extract exact traces of I/O operations in Oracle. Since there are only write operations in the log, it is impossible to gather read operations. In MySQL and SQLite, we can gather the read operations by changing I/O functions in the source codes. But it is not easy to search for the exact points about I/O and even if we can find out the points, we might get wrong results depending on how we modify source codes to get I/O traces. The FlaSim proposed in this paper removes the difficulties when we evaluate the performance of FTL algorithms and flash memory. Our Linux drivers emulate the flash memory as a hard disk. And we can easily obtain the usage statistics of flash memory such as the number of write, read, and erase operations. The FlaSim can be gracefully extended to support the additional modules implemented by novel algorithms and ideas. In this paper, we describe the structure of FTL emulator, development tools and operating methods. We expect this emulator to be helpful for many experiments and research with flash memory.
With the recent growth of the AI speaker market, the demand for speech synthesis technology that enables natural conversation with users is increasing. Therefore, there is a need for a multi-speaker speech synthesis system that can generate voices of various tones. In order to synthesize natural speech, it is required to train with a large-capacity. high-quality speech DB. However, it is very difficult in terms of recording time and cost to collect a high-quality, large-capacity speech database uttered by many speakers. Therefore, it is necessary to train the speech synthesis system using the speech DB of a very large number of speakers with a small amount of training data for each speaker, and a technique for naturally expressing the tone and rhyme of multiple speakers is required. In this paper, we propose a technology for constructing a speaker encoder by applying the deep learning-based x-vector technique used in speaker recognition technology, and synthesizing a new speaker's tone with a small amount of data through the speaker encoder. In the multi-speaker speech synthesis system, the module for synthesizing mel-spectrogram from input text is composed of Tacotron2, and the vocoder generating synthesized speech consists of WaveNet with mixture of logistic distributions applied. The x-vector extracted from the trained speaker embedding neural networks is added to Tacotron2 as an input to express the desired speaker's tone.
The new medical device technologies for bio-signal information and medical information which developed in various forms have been increasing. Information gathering techniques and the increasing of the bio-signal information device are being used as the main information of the medical service in everyday life. Hence, there is increasing in utilization of the various bio-signals, but it has a problem that does not account for security reasons. Furthermore, the medical image information and bio-signal of the patient in medical field is generated by the individual device, that make the situation cannot be managed and integrated. In order to solve that problem, in this paper we integrated the QR code signal associated with the medial image information including the finding of the doctor and the bio-signal information. bio-signal. System implementation environment for medical imaging devices and bio-signal acquisition was configured through bio-signal measurement, smart device and PC. For the ROI extraction of bio-signal and the receiving of image information that transfer from the medical equipment or bio-signal measurement, .NET Framework was used to operate the QR server module on Window Server 2008 operating system. The main function of the QR server module is to parse the DICOM file generated from the medical imaging device and extract the identified ROI information to store and manage in the database. Additionally, EMR, patient health information such as OCS, extracted ROI information needed for basic information and emergency situation is managed by QR code. QR code and ROI management and the bio-signal information file also store and manage depending on the size of receiving the bio-singnal information case with a PID (patient identification) to be used by the bio-signal device. If the receiving of information is not less than the maximum size to be converted into a QR code, the QR code and the URL information can access the bio-signal information through the server. Likewise, .Net Framework is installed to provide the information in the form of the QR code, so the client can check and find the relevant information through PC and android-based smart device. Finally, the existing medical imaging information, bio-signal information and the health information of the patient are integrated over the result of executing the application service in order to provide a medical information service which is suitable in medical field.
The wall shear stress in the vicinity of end-to end anastomoses under steady flow conditions was measured using a flush-mounted hot-film anemometer(FMHFA) probe. The experimental measurements were in good agreement with numerical results except in flow with low Reynolds numbers. The wall shear stress increased proximal to the anastomosis in flow from the Penrose tubing (simulating an artery) to the PTFE: graft. In flow from the PTFE graft to the Penrose tubing, low wall shear stress was observed distal to the anastomosis. Abnormal distributions of wall shear stress in the vicinity of the anastomosis, resulting from the compliance mismatch between the graft and the host artery, might be an important factor of ANFH formation and the graft failure. The present study suggests a correlation between regions of the low wall shear stress and the development of anastomotic neointimal fibrous hyperplasia(ANPH) in end-to-end anastomoses. 30523 T00401030523 ^x Air pressure decay(APD) rate and ultrafiltration rate(UFR) tests were performed on new and saline rinsed dialyzers as well as those roused in patients several times. C-DAK 4000 (Cordis Dow) and CF IS-11 (Baxter Travenol) reused dialyzers obtained from the dialysis clinic were used in the present study. The new dialyzers exhibited a relatively flat APD, whereas saline rinsed and reused dialyzers showed considerable amount of decay. C-DAH dialyzers had a larger APD(11.70
The wall shear stress in the vicinity of end-to end anastomoses under steady flow conditions was measured using a flush-mounted hot-film anemometer(FMHFA) probe. The experimental measurements were in good agreement with numerical results except in flow with low Reynolds numbers. The wall shear stress increased proximal to the anastomosis in flow from the Penrose tubing (simulating an artery) to the PTFE: graft. In flow from the PTFE graft to the Penrose tubing, low wall shear stress was observed distal to the anastomosis. Abnormal distributions of wall shear stress in the vicinity of the anastomosis, resulting from the compliance mismatch between the graft and the host artery, might be an important factor of ANFH formation and the graft failure. The present study suggests a correlation between regions of the low wall shear stress and the development of anastomotic neointimal fibrous hyperplasia(ANPH) in end-to-end anastomoses. 30523 T00401030523 ^x Air pressure decay(APD) rate and ultrafiltration rate(UFR) tests were performed on new and saline rinsed dialyzers as well as those roused in patients several times. C-DAK 4000 (Cordis Dow) and CF IS-11 (Baxter Travenol) reused dialyzers obtained from the dialysis clinic were used in the present study. The new dialyzers exhibited a relatively flat APD, whereas saline rinsed and reused dialyzers showed considerable amount of decay. C-DAH dialyzers had a larger APD(11.70
Recently, as economic property it has become necessary to acquire and utilize the framework for water resource measurement and performance management as the property of water resources changes to hold "public property". To date, the evaluation of water technology has been carried out by feasibility study analysis or technology assessment based on net present value (NPV) or benefit-to-cost (B/C) effect, however it is not yet systemized in terms of valuation models to objectively assess an economic value of technology-based business to receive diffusion and feedback of research outcomes. Therefore, K-water (known as a government-supported public company in Korea) company feels the necessity to establish a technology valuation framework suitable for technical characteristics of water resources fields in charge and verify an exemplified case applied to the technology. The K-water evaluation technology applied to this study, as a public interest goods, can be used as a tool to measure the value and achievement contributed to society and to manage them. Therefore, by calculating the value in which the subject technology contributed to the entire society as a public resource, we make use of it as a basis information for the advertising medium of performance on the influence effect of the benefits or the necessity of cost input, and then secure the legitimacy for large-scale R&D cost input in terms of the characteristics of public technology. Hence, K-water company, one of the public corporation in Korea which deals with public goods of 'water resources', will be able to establish a commercialization strategy for business operation and prepare for a basis for the performance calculation of input R&D cost. In this study, K-water has developed a web-based technology valuation model for public interest type water resources based on the technology evaluation system that is suitable for the characteristics of a technology in water resources fields. In particular, by utilizing the evaluation methodology of the Institute of Advanced Industrial Science and Technology (AIST) in Japan to match the expense items to the expense accounts based on the related benefit items, we proposed the so-called 'K-water's proprietary model' which involves the 'cost-benefit' approach and the FCF (Free Cash Flow), and ultimately led to build a pipeline on the K-water research performance management system and then verify the practical case of a technology related to "desalination". We analyze the embedded design logic and evaluation process of web-based valuation system that reflects characteristics of water resources technology, reference information and database(D/B)-associated logic for each model to calculate public interest-based and profit-based technology values in technology integrated management system. We review the hybrid evaluation module that reflects the quantitative index of the qualitative evaluation indices reflecting the unique characteristics of water resources and the visualized user-interface (UI) of the actual web-based evaluation, which both are appended for calculating the business value based on financial data to the existing web-based technology valuation systems in other fields. K-water's technology valuation model is evaluated by distinguishing between public-interest type and profitable-type water technology. First, evaluation modules in profit-type technology valuation model are designed based on 'profitability of technology'. For example, the technology inventory K-water holds has a number of profit-oriented technologies such as water treatment membranes. On the other hand, the public interest-type technology valuation is designed to evaluate the public-interest oriented technology such as the dam, which reflects the characteristics of public benefits and costs. In order to examine the appropriateness of the cost-benefit based public utility valuation model (i.e. K-water specific technology valuation model) presented in this study, we applied to practical cases from calculation of benefit-to-cost analysis on water resource technology with 20 years of lifetime. In future we will additionally conduct verifying the K-water public utility-based valuation model by each business model which reflects various business environmental characteristics.