DA-5018 is a synthetic capsaicin derivative under development as a non-narcotic a analgesic ag$\varepsilon$nt. DA-50 18 showed a potent analgesic activity against acute and chronic pain m model(Tablel, 2.), but it had a narrow margin of safety. DA-5018 did not bind to opioid(${\kappa}, {\delta}, {\mu}$), NKl, CGRP receptors in vitro and its analgesic effect was not antagonized by naloxone, a and it did not develop analgesic tolerance. In addition DA-5018 had no inhibitory effects against c cyclooxygenase and 5-lipooxygenase activities. DA-5018 significantly increased the relcase of substance P from the slices of the rat spinal cord. These results suggest that DA-50 18 is not a narcotic nor aspirin-like analgesic and the release of substance P is one of analgesic mechanism of action of DA-5018. We found that DA-5018 was almost ten times more potent and was at l least IOO-times less irritable compared to capsaicin. Accordingly development of topical formula was adopted. Topical formula was desiged and screened by flux test of DA-5018 using hairless mouse skin and several formulas were selected. With these topical formulas we a assessed the analgesic efficacy and carried out the toxicity, skin irritation and pharmacokinetic studies. In streptozotocin-induced hyperalgesic rat and 50 % galactose-fed hyperalgesic rat as diabetic pain models, DA-5018 cream increased the pain thresh이ds up to 77.0% and 24.4% respectively, while Zostrix-HP(capsaicin cream) incr$\varepsilon$as cd by 65.9% and 21.0%. DA-5018 c cream showed a good analgesic effect as welI in FCA-induced arthritic rat. DA-5018 cream did not show any toxicological signs in acute and chronic toxicity test and had little skin irritation in car swclIing and scratching t$\varepsilon$st. Pharmacokinetics of DA-50 18 were studied after topical application of ${14}^C$-Iabelled or unlabelIed DA-5018 cream. Plasma and skin concentrations c except applied skin wcre below the dctection limit and after 7-day cummulative application, plasma concentrations were also below detection limit DA-50 18 may have an advantag$\varepsilon$ ov$\varepsilon$r c capsaicin and is now being developed as a topical agent for the treatment of pains. DA-50 18 cream was approved for Korean IND and is now under a Phase II clinical study for arthritic pain a after finising Phase I study. DA-50 18 was also liscensed out to Stiefel Company in America in
This article reviews recent developments in three-dimensional (3-D) magntotelluric (MT) imaging. The inversion of MT data is fundamentally ill-posed, and therefore the resultant solution is non-unique. A regularizing scheme must be involved to reduce the non-uniqueness while retaining certain a priori information in the solution. The standard approach to nonlinear inversion in geophysis has been the Gauss-Newton method, which solves a sequence of linearized inverse problems. When running to convergence, the algorithm minimizes an objective function over the space of models and in the sense produces an optimal solution of the inverse problem. The general usefulness of iterative, linearized inversion algorithms, however is greatly limited in 3-D MT applications by the requirement of computing the Jacobian(partial derivative, sensitivity) matrix of the forward problem. The difficulty may be relaxed using conjugate gradients(CG) methods. A linear CG technique is used to solve each step of Gauss-Newton iterations incompletely, while the method of nonlinear CG is applied directly to the minimization of the objective function. These CG techniques replace computation of jacobian matrix and solution of a large linear system with computations equivalent to only three forward problems per inversion iteration. Consequently, the algorithms are efficient in computational speed and memory requirement, making 3-D inversion feasible.
In this paper, the wind tunnel test for the measurement of aerodynamic characteristics of transmission conductors with asymmetric sections is described. A single conductor model and bundled conductor models with ice accreted shapes are tested both in steady and turbulent flow, and the aerodynamic coefficients are acquired. Transmission conductor galloping is a kind of wind-induced vibration which is characterized by primarily vertical oscillation with a very low frequency and a high amplitude. It is well known that transmission conductor galloping is generally caused by moderately strong, steady winds when a transmission conductor has an asymmetric cross-section shaped by accreted ice. Galloping should be considered from the design stage of overhead lines because it can cause severe wear and fatigue damage to attachments as well as transmission conductors. It is reported that there have been normally 20 events of galloping per year in Korea, which may be followed by serious consequences in the electric power system. Therefore, this research is performed to measure aerodynamic characteristics of ice accreted transmission conductors to understand and control transmission conductor galloping so that it would help to prevent unexpected failures and reduce the maintenance costs caused by galloping.
Journal of the Computational Structural Engineering Institute of Korea
/
v.30
no.4
/
pp.329-334
/
2017
The structures, which are made up with the huge number of degrees-of-freedom and the assembly of substructures, have a great complexity. In order to increase the computational efficiency, the analysis models have to be simplified. Many substructuring techniques have been developed to simplify large-scale engineering problems. The techniques are very powerful for solving nonlinear problems which require many iterative calculations. In this paper, a modal derivatives-based model order reduction method, which is able to capture the stretching-bending coupling behavior in geometrically nonlinear systems, is adopted and investigated for its performance evaluation. The quadratic terms in nonlinear beam theory, such as Green-Lagrange strains, can be explained by the modal derivatives. They can be obtained by taking the modal directional derivatives of eigenmodes and form the second order terms of modal reduction basis. The method proposed is then applied to a co-rotational finite element formulation that is well-suited for geometrically nonlinear problems. Numerical results reveal that the end-shortening effect is very important, in which a conventional modal reduction method does not work unless the full model is used. It is demonstrated that the modal derivative approach yields the best compromised result and is very promising for substructuring large-scale geometrically nonlinear problems.
A gas turbine engine plays an important role as a prime mover that is used in the marine transportation field as well as the space/aviation and power plant fields. However, it has a complicated structure and there is a time delay element in the combustion process. Therefore, an elaborate mathematical model needs to be developed to control a gas turbine engine. In this study, a modeling technique for a gas generator, a PLA actuator, and a metering valve, which are major components of a gas turbine engine, is explained. In addition, sub-models are obtained at several operating points in a steady state based on the trial running data of a gas turbine engine, and a method for controlling the engine speed is proposed by designing an NPID controller for each sub-model. The proposed NPID controller uses three kinds of gains that are implemented with a nonlinear function. The parameters of the NPID controller are tuned using real-coded genetic algorithms in terms of minimizing the objective function. The validity of the proposed method is examined by applying to a gas turbine engine and by conducting a simulation.
The major goals of periodontal therapy is the functional regeneration of periodontal supporting structures already destructed by periodontal disease as well as the reduction of signs and symptoms of progressive periodontal disease. There have been many efforts to develop materials and therapeutic methods to promote periodontal wound healing. There have been increasing interest on the chitosan made by chitin. Chitin is second only to cellulose as the most abundant natural biopolymer. It is a structural component of the exoskeleton of invertebrates(e.g., shrimp, crabs, lobsters), of the cell wall of fungi, and of the cuticle of insects. Chitosan is a derivative of chitin made by deacetylation of side chains. Many experiments using chitosan in various animal models have proven its beneficial effects. The aim of this study is to evaluate the osteogenesis of chitosan on the calvarial critical size defect in Sprague Dawley rats. An 8 mm surgical defect was produced with a trephine bur in the area of the midsagittal suture. The rats were divided into two groups: Untreated control group versus experimental group with 50mg of soluble chitosan gel. The animals were sacrificed at 2, 4 and 8 weeks after surgical procedure. The specimens were examined by histologic, histomorphometric and radiodensitometric analyses. The results are as follows: 1. The length of newly formed bone in the defects was $102.91{\pm}25.46{\mu}m$, $219.46{\pm}97.81{\mu}m$ at the 2 weeks, $130.95{\pm}39.24{\mu}m$, $212.39{\pm}89.22{\mu}m$ at the 4 weeks, $181.53{\pm}76.35{\mu}m$ and $257.12{\pm}51.22{\mu}m$ at the 8 weeks in the control group and experimental group respectively. At all periods, the means of experimental group was greater than those of control group. But, there was no statistically significant difference between the two groups. 2. The area of newly formed bone in the defects was $2962.06{\pm}1284.48{\mu}m^2$, $5194.88{\pm}1247.88{\mu}m^2$ at the 2 weeks, $5103.25{\pm}1375.88{\mu}m^2$, $7751.43{\pm}2228.20{\mu}m^2$ at the 4 weeks and $8046.20{\pm}818.99{\mu}m^2$, $15578.57{\pm}5606.55{\mu}m^2$ at the 8 weeks in the control group and experimental group respectively. At all periods, the means of experimental group was greater than those of control group. The experimental group showed statistically significant difference to the control group at the 2 and 8 weeks. 3. The density of newly formed bone in the defects was $14.26{\pm}6.33%$, $27.91{\pm}6.65%$ at the 2 weeks, $20.06{\pm}9.07%$, $27.86{\pm}8.20%$ at the 4 weeks and $22.99{\pm}3.76%$, $32.17{\pm}6.38%$ at the 8 weeks in the control group and experimental group respectively. At all periods, the means of experimental group was greater than those of control group. The experimental group showed statistically significant difference to the control group at the 2 and 8 weeks. These results suggest that the use of chitosan on the calvarial defects in rats has significant effect on the regeneration of bone tissue in itself
The major goals of periodontal therapy are the functional regeneration of periodontal supporting structures already destructed by periodontal disease as well as the reduction of signs and symptoms of progressive periodontal disease. There have been many efforts to develop materials and therapeutic methods to promote periodontal wound healing. There have been increasing interest on the chitosan made by chtin. Chitosan is a derivative of chitin made by deacetylation of side chains. Chitosan has been widely studied as bone substitution and membrane material in periodontology. Many experiments using chitosan in various animal models have proven its beneficial effects. Tetracycline has been considered for use in the treatment of chronic periodontal disease and gingivitis. The aim of this study is to evlauate the osteogenesis of tetracycline blended chitosan membranes on the calvarial critical size defect in Sprague Dawley rats. An 8mm surgical defect was produced with a trephine bur in the area of the midsagittal suture. The rats were divided into five groups: Untreated control group versus four experimental group. Four types of membranes were made and comparative study was been done. Two types of non-woven membranes were made by immersing non-woven chitosan into either the tetracycline solution or chitosan-tetracycline solution. Other two types of sponge membranes were fabricated by immersing chitosan sponge into the tetracycline solution, and subsequent freeze-drying. The animals were sacrificed at 2 and 8 weeks after surgical procedure. The specimens were examined by histologic analyses. The results are as follows: 1. Clinically the use of tetracycline blended chitosan membrane showed great healing capacity. 2. The new bone formations of all the experimental group, non-woven and sponge type membranes were greater than those of control group. But, there was no significant difference between the experimental groups. 3. Resorption of chitosan membranes were not shown in any groups at 2 weeks and 8 weeks. These results suggest that the use of tetracycline blended chitosan membrane on the calvarial defects in rats has significant effect on the regeneration of bone tissue in itself. And it implicate that tetracycline blended chitosan membrane might be useful for guided tissue regeneration.
Purpose: The balance between synthesis and degradation of proteins plays a critical role in the maintenance of skeletal muscle mass. Mitochondrial dysfunction has been closely associated with skeletal muscle atrophy caused by aging, cancer, and chemotherapy. Polygalacin D is a saponin derivative isolated from Platycodon grandiflorum (Jacq.) A. DC. This study aimed to investigate the effects of polygalacin D on myoblast differentiation and muscle atrophy in association with mitochondrial function in in vitro and in zebrafish models in vivo. Methods: C2C12 myoblasts were cultured in differentiation media containing different concentrations of polygalacin D, followed by the immunostaining of the myotubes with myosin heavy chain (MHC). The mRNA expression of markers related to myogenesis, muscle atrophy, and mitochondrial function was determined by real-time quantitative reverse transcription polymerase chain reaction. Wild type AB* zebrafish (Danio rerio) embryos were treated with 5-fluorouracil, leucovorin, and irinotecan (FOLFIRI) with or without polygalacin D, and immunostained to detect slow and fast types of muscle fibers. The Tg(Xla.Eef1a1:mitoEGFP) zebrafish expressing mitochondria-targeted green fluorescent protein was used to monitor mitochondrial morphology. Results: The exposure of C2C12 myotubes to 0.1 ng/mL of polygalacin D increased the formation of MHC-positive multinucleated myotubes (≥ 8 nuclei) compared with the control. Polygalacin D significantly increased the expression of MHC isoforms (Myh1, Myh2, Myh4, and Myh7) involved in myoblast differentiation while it decreased the expression of atrophic markers including muscle RING-finger protein-1 (MuRF1), mothers against decapentaplegic homolog (Smad)2, and Smad3. In addition, polygalacin D promoted peroxisome proliferator-activated receptor-gamma coactivator (Pgc1α) expression and reduced the level of mitochondrial fission regulators such as dynamin-1-like protein (Drp1) and mitochondrial fission 1 (Fis1). In a zebrafish model of FOLFIRI-induced muscle atrophy, polygalacin D improved not only mitochondrial dysfunction but also slow and fast muscle fiber atrophy. Conclusion: These results demonstrated that polygalacin D promotes myogenesis and alleviates chemotherapy-induced muscle atrophy by improving mitochondrial function. Thus, polygalacin D could be useful as nutrition support to prevent and ameliorate muscle wasting and weakness.
Market timing is an investment strategy which is used for obtaining excessive return from financial market. In general, detection of market timing means determining when to buy and sell to get excess return from trading. In many market timing systems, trading rules have been used as an engine to generate signals for trade. On the other hand, some researchers proposed the rough set analysis as a proper tool for market timing because it does not generate a signal for trade when the pattern of the market is uncertain by using the control function. The data for the rough set analysis should be discretized of numeric value because the rough set only accepts categorical data for analysis. Discretization searches for proper "cuts" for numeric data that determine intervals. All values that lie within each interval are transformed into same value. In general, there are four methods for data discretization in rough set analysis including equal frequency scaling, expert's knowledge-based discretization, minimum entropy scaling, and na$\ddot{i}$ve and Boolean reasoning-based discretization. Equal frequency scaling fixes a number of intervals and examines the histogram of each variable, then determines cuts so that approximately the same number of samples fall into each of the intervals. Expert's knowledge-based discretization determines cuts according to knowledge of domain experts through literature review or interview with experts. Minimum entropy scaling implements the algorithm based on recursively partitioning the value set of each variable so that a local measure of entropy is optimized. Na$\ddot{i}$ve and Booleanreasoning-based discretization searches categorical values by using Na$\ddot{i}$ve scaling the data, then finds the optimized dicretization thresholds through Boolean reasoning. Although the rough set analysis is promising for market timing, there is little research on the impact of the various data discretization methods on performance from trading using the rough set analysis. In this study, we compare stock market timing models using rough set analysis with various data discretization methods. The research data used in this study are the KOSPI 200 from May 1996 to October 1998. KOSPI 200 is the underlying index of the KOSPI 200 futures which is the first derivative instrument in the Korean stock market. The KOSPI 200 is a market value weighted index which consists of 200 stocks selected by criteria on liquidity and their status in corresponding industry including manufacturing, construction, communication, electricity and gas, distribution and services, and financing. The total number of samples is 660 trading days. In addition, this study uses popular technical indicators as independent variables. The experimental results show that the most profitable method for the training sample is the na$\ddot{i}$ve and Boolean reasoning but the expert's knowledge-based discretization is the most profitable method for the validation sample. In addition, the expert's knowledge-based discretization produced robust performance for both of training and validation sample. We also compared rough set analysis and decision tree. This study experimented C4.5 for the comparison purpose. The results show that rough set analysis with expert's knowledge-based discretization produced more profitable rules than C4.5.
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