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Toxicokinetics of paraquat in Korean patients with acute poisoning

  • Kim, Hak-Jae;Kim, Hyung-Ki;Lee, Hwayoung;Bae, Jun-Seok;Kown, Jun-Tack;Gil, Hyo-Wook;Hong, Sae-Yong
    • The Korean Journal of Physiology and Pharmacology
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    • v.20 no.1
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    • pp.35-39
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    • 2016
  • To conduct a kinetic study of paraquat (PQ), we investigated 9 patients with acute PQ intoxication. All of them ingested more than 20 ml of undiluted PQ herbicide to commit suicide and arrived at our hospital early, not later than 7 h after PQ ingestion. The urine dithionite test for PQ in all of the nine patients was strongly positive at emergency room. Blood samples were obtained every 30 min for the first 2~3 h and then every 1 or 2 h, as long as the clinical progression was stable among the patients for 30 h after PQ ingestion. The area under the plasma concentration-time curve ($AUC_{inf}$), which was extrapolated to infinity, was calculated using the trapezoidal rule. Toxicokinetic parameters, such as the terminal elimination half-life, apparent oral clearance, and apparent volume of distribution ($V_d/F$) were calculated. The maximum PQ concentration ($C_{max}$) and the time to reach maximum PQ concentration ($T_{max}$) were also obtained. Plasma PQ concentrations in nine patients were well described by a bi-exponential curve with a mean terminal elimination half-life of $13.1{\pm}6.8h$. $C_{max}$ and $AUC_{inf}$ were $20.8{\pm}25.7mg/l$ and $172.5{\pm}160.3h{\cdot}mg/l$, respectively. Apparent volume of distribution and apparent oral clearance were $50.9{\pm}61.3l/kg$ and $173.4{\pm}111.2l/h$, respectively. There were a significant correlation (r=0.84; p<0.05) between the PQ amount ingested and $C_{max}$. $AUC_{inf}$ also showed a significant correlation (r=0.83; p<0.05) with the PQ amount ingested. These correlations provide evidence that PQ has dose-linear toxicokinetic characteristics.

Bioequivalence of Efexor® XR capsule to Venfaxine® OR tablet (Venlafaxine 75 mg) (이팩사® XR서방캅셀(벤라팍신, 75 mg)에 대한 벤팍신®OR서방정의 생물학적동등성)

  • Aryal, Dipendra Kumar;Oh, Soo-Yeon;Cho, Jong-Tae;Kim, Hyung-Gun;Kim, Yoon-Gyoon
    • Journal of Pharmaceutical Investigation
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    • v.37 no.6
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    • pp.397-402
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    • 2007
  • To evaluate the bioequivalence of two venlafaxine formulations, a standard 2-way randomized cross-over study was conducted in twenty-four healthy male Korean volunteers. A single oral dose of 75 mg of test formulation Venfaxine $OR^{(R)}$ (tablet) or reference formulation Efexor $XR^{(R)}$ (capsule) was administered with one-week washout period. Plasma concentrations of venlafaxine were assayed for over a period of 72 hours with a well validated method using liquid chromatography coupled to tandem mass spectrometry (LC-MS-MS). The $mean{\pm}S.D$. of maximum concentration $(C_{max})$ and elimination half-life $(t_{1/2})$ were $64.7{\pm}28.5$ ng/mL, $9.2{\pm}3.0$ h, and $67.2{\pm}30.2$ ng/mL, $9.9{\pm}3.5$ h for test and reference formulations, respectively. Time to reach maximum concentration $(T_{max})$ expressed in median value (range), for the test and the reference, were 10 h (6-14) and 8h (4-12), respectively. Similarly, area under the plasma concentration-time curve, from time zero to last sampling time $(AUC_t)$ and from time zero to time infinity $(AUC_{inf})$, for test and reference formulations were $1185{\pm}755$, $1326{\pm}896$ and $1124{\pm}737$, $1185{\pm}755$ $ng{\cdot}h/mL$, respectively. The parametric 90% confidence intervals on the mean of the differences between the two formulations (test-reference) of the log transformed values of $AUC_t$, and $C_{max}$ were 0.9630 to 1.1383 and 0.8650 to 1.0446, respectively. The overall results indicate that the two formulations are bioequivalent and can be prescribe interchangeably.

A Design of 2 DOF PID Controller Using Performance Index (평가지표를 이용한 2자유도 PID제어기 설계)

  • 유항열;이정국;이금원;이준모
    • Journal of the Institute of Convergence Signal Processing
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    • v.5 no.1
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    • pp.66-72
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    • 2004
  • PID control has been well used for several decades. For PID algorithms, some tuning methods are used for selecting PID parameters and with these selected parameters, PID control system is designed. But in some cases various kinds of performance indices are used instead of well-known tuning rules, and so variable type of performance index must be tested so that the designed control system meets the some specifications. For 2 DOF PID controller design this paper presents a linear combinational type of performance indices constituting of index for robust performance, which is obtained by h infinity norm of a weighted complementary sensitivity function, including other time domain indices such as error, energy and changing rate of control input. By numerical methods, the optimal 2 DOF PID parameters are obtained. Therefore various types of 2 degree of freedom PID controllers such as I-PD controller are used so that this two degree of freedom PID controllers may give more desirable output characteristics. Simulations are done with MATLAB m file and mdl files.

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Hydrogen Perm-Selectivity Property of the Palladium Hydrogen Separation Membranes on Porous Stainless Steel Support Manufactured by Metal Injection Molding (금속 사출성형 방식의 다공성 스테인리스 강 지지체에 형성된 팔라듐 수소 분리막의 투과 선택도 특성)

  • Kim, Se-Hong;Yang, Ji-Hye;Lim, Da-Sol;Kim, Dong-Won
    • Journal of Surface Science and Engineering
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    • v.50 no.2
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    • pp.98-107
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    • 2017
  • Pd-based membranes have been widely used in hydrogen purification and separation due to their high hydrogen diffusivity and infinite selectivity. However, it has been difficult to fabricate thin and dense Pd-based membranes on a porous stainless steel(PSS) support. In case of a conventional PSS support having the large size of surface pores, it was required to use complex surface treatment and thick Pd coating more than $6{\mu}m$ on the PSS was required in order to form pore free surface. In this study, we could fabricate thin and dense Pd membrane with only $3{\mu}m$ Pd layer on a new PSS support manufactured by metal injection molding(MIM). The PSS support had low surface roughness and mean pore size of $5{\mu}m$. Pd membrane were prepared by advanced Pd sputter deposition on the modified PSS support using fine polishing and YSZ vacuum filling surface treatment. At temperature $400^{\circ}C$ and transmembrane pressure difference of 1 bar, hydrogen flux and selectivity of $H_2/N_2$ were $11.22ml\;cm^{-2}min^{-1}$ and infinity, respectively. Comparing with $6{\mu}m$ Pd membrane, $3{\mu}m$ Pd membrane showed 2.5 times higher hydrogen flux which could be due to the decreased Pd layer thickness from $6{\mu}m$ to $3{\mu}m$ and an increased porosity. It was also found that pressure exponent was changed from 0.5 on $6{\mu}m$ Pd membrane to 0.8 on $3{\mu}m$ Pd membrane.

Bioequivalence Evaluation of the Cisapride Formulation Produced by Dong Wha Pharmaceutical Co. (동화약품 시사프리드제제의 생물학적 동등성 평가)

  • 윤광희;박진영;박선주;조은희;유제만;김경식;정석재;이민화;심창구
    • Biomolecules & Therapeutics
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    • v.7 no.1
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    • pp.59-65
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    • 1999
  • A bioequivalence study of the Dong Wha Cisapril tablets(Dong Wha Pharm. Ind. Co., Ltd.) to the Prepulsid tablets(Janssen Korea Ltd.), formulations of cisapride, was conducted. Twenty four healthy Korean male subjects received each formulation at the dose of 5 mg as cisapride in a 2$\times$2 crossover study. There was a 1-week washout period between the doses. Plasma concentrations of cisapride were monitored by an LC/MS method for over a period of 36 h after each administration. AUC(area under the plasma concentration- time curve from time zero to infinity) was calculated by the linear trapezoidal and extrapolation method. $C_{max}$ (maximum plasma drug concentration) and $T_{max}$ (time to reach $C_{max}$) were compiled from the plasma drug concentration-time data. Analysis of variance (ANOVA) revealed that there are no differences in AUC, $C_{max}$ and $T_{max}$ between the formulations. The apparent differences between the formulations in these parameters were all far less than 20% (i.e., 6.8, -6.6 and 1.8% for AUC, $C_{max}$ and $T_{max}$, respectively). Minimum detectable differences(%) at $\alpha$=0.05 and 1-$\beta$=0.8 were all less than 20% in these parameters between the formulations (i.e., 16.5, 11.4 and 16.4% for AUC, $C_{max}$ and $T_{max}$, respectively). The 90% confidence intervals for these parameters were also within 20% (i.e., -2.9~ 16.4, -13.2~0.1 and -7.8~ 11.4% for AUC, $C_{max}$ and $T_{max}$, respectively). These results satisfy the bioequivalence criteria of the Korea Food and Drug Administration (KFDA) guidelines (No. 98-51). Therefore, these results indicate that the two formulations of cisapride are bioequivalent and, thus, may be prescribed interchangeably.hangeably.y.hangeably.

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Fuzzy neural network controller of interconnected method for civil structures

  • Chen, Z.Y.;Meng, Yahui;Wang, Ruei-yuan;Chen, Timothy
    • Advances in concrete construction
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    • v.13 no.5
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    • pp.385-394
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    • 2022
  • Recently, an increasing number of cutting-edged studies have shown that designing a smart active control for real-time implementation requires piles of hard-work criteria in the design process, including performance controllers to reduce the tracking errors and tolerance to external interference and measure system disturbed perturbations. This article proposes an effective artificial-intelligence method using these rigorous criteria, which can be translated into general control plants for the management of civil engineering installations. To facilitate the calculation, an efficient solution process based on linear matrix (LMI) inequality has been introduced to verify the relevance of the proposed method, and extensive simulators have been carried out for the numerical constructive model in the seismic stimulation of the active rigidity. Additionally, a fuzzy model of the neural network based system (NN) is developed using an interconnected method for LDI (linear differential) representation determined for arbitrary dynamics. This expression is constructed with a nonlinear sector which converts the nonlinear model into a multiple linear deformation of the linear model and a new state sufficient to guarantee the asymptomatic stability of the Lyapunov function of the linear matrix inequality. In the control design, we incorporated H Infinity optimized development algorithm and performance analysis stability. Finally, there is a numerical practical example with simulations to show the results. The implication results in the RMS response with as well as without tuned mass damper (TMD) of the benchmark building under the external excitation, the El-Centro Earthquake, in which it also showed the simulation using evolved bat algorithmic LMI fuzzy controllers in term of RMS in acceleration and displacement of the building.

LOW REGULARITY SOLUTIONS TO HIGHER-ORDER HARTREE-FOCK EQUATIONS WITH UNIFORM BOUNDS

  • Changhun Yang
    • Journal of the Chungcheong Mathematical Society
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    • v.37 no.1
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    • pp.27-40
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    • 2024
  • In this paper, we consider the higher-order HartreeFock equations. The higher-order linear Schrödinger equation was introduced in [5] as the formal finite Taylor expansion of the pseudorelativistic linear Schrödinger equation. In [13], the authors established global-in-time Strichartz estimates for the linear higher-order equations which hold uniformly in the speed of light c ≥ 1 and as their applications they proved the convergence of higher-order Hartree-Fock equations to the corresponding pseudo-relativistic equation on arbitrary time interval as c goes to infinity when the Taylor expansion order is odd. To achieve this, they not only showed the existence of solutions in L2 space but also proved that the solutions stay bounded uniformly in c. We address the remaining question on the convergence of higherorder Hartree-Fock equations when the Taylor expansion order is even. The distinguished feature from the odd case is that the group velocity of phase function would be vanishing when the size of frequency is comparable to c. Owing to this property, the kinetic energy of solutions is not coercive and only weaker Strichartz estimates compared to the odd case were obtained in [13]. Thus, we only manage to establish the existence of local solutions in Hs space for s > $\frac{1}{3}$ on a finite time interval [-T, T], however, the time interval does not depend on c and the solutions are bounded uniformly in c. In addition, we provide the convergence result of higher-order Hartree-Fock equations to the pseudo-relativistic equation with the same convergence rate as the odd case, which holds on [-T, T].

Effect of B-complex vitamins on the antifatigue activity and bioavailability of ginsenoside Re after oral administration

  • Chen, Yin Bin;Wang, Yu Fang;Hou, Wei;Wang, Ying Ping;Xiao, Sheng Yuan;Fu, Yang Yang;Wang, Jia;Zheng, Si Wen;Zheng, Pei He
    • Journal of Ginseng Research
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    • v.41 no.2
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    • pp.209-214
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    • 2017
  • Background: Both ginsenoside Re and B-complex vitamins are widely used as nutritional supplements. They are often taken together so as to fully utilize their antifatigue and refreshing effects, respectively. Whether actually a drug-nutrient interaction exists between ginsenoside Re and B-complex vitamins is still unknown. The objective of this study was to simultaneously investigate the effect of B-complex vitamins on the antifatigue activity and bioavailability of ginsenoside Re after their oral administration. The study results will provide valuable theoretical guidance for the combined utilization of ginseng and B-complex vitamins. Methods: Ginsenoside Re with or without B-complex vitamins was orally administered to mice to evaluate its antifatigue effects and to rats to evaluate its bioavailability. The antifatigue activity was evaluated by the weight-loaded swimming test and biochemical parameters, including hepatic glycogen, plasma urea nitrogen, and blood lactic acid. The concentration of ginsenoside Re in plasma was determined by liquid chromatography-tandem mass spectrometry. Results: No antifatigue effect of ginsenoside Re was noted when ginsenoside Re in combination with B-complex vitamins was orally administered to mice. B-complex vitamins caused to a reduction in the bioavailability of ginsenoside Re with the area under the concentration-time curve from zero to infinity markedly decreasing from $11,830.85{\pm}2,366.47h{\cdot}ng/mL$ to $890.55{\pm}372.94h{\cdot}ng/mL$. Conclusion: The results suggested that there were pharmacokinetic and pharmacodynamic drug-nutrient interactions between ginsenoside Re and B-complex vitamins. B-complex vitamins can significantly weaken the antifatigue effect and decrease the bioavailability of ginsenoside Re when simultaneously administered orally.

Bioequivalence of Loxipen Tablet to Loxonin Tablet (Sodium Loxoprofen Anhydride 60 mg) (록소닌 정(록소프로펜 나트륨 무수물 60 mg)에 대한 록시펜 정의 생물학적 동등성)

  • Kim, In-Wha;Han, Tae-Gyu;Kim, Kyung-Sik;Chung, Suk-Jae;Lee, Min-Hwa;Shim, Chang-Koo
    • Journal of Pharmaceutical Investigation
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    • v.28 no.3
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    • pp.185-191
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    • 1998
  • A bioequivalence study of the Loxipen tablets (Dae Wha Pharmaceutical Co., Korea) to the Loxonin tablets (Dong Hwa Pharmaceutical Co., Korea), formulations of sodium loxoprofen anhydrous 60 mg, was conducted. Sixteen healthy Korean male subjects received each formulation at the dose of 60 mg as sodium loxoprofen anhydrous in a $2{\times}2$ crossover study. There was a 2-week washout period between the dose. Plasma concentrations of loxoprofen were monitored by an HPLC method for over a period of 6 h after each administration. AUC (area under the plasma concentration-time curve from time zero to infinity) was calculated by the linear trapezoidal and extrapolation method. $C_{max}$ (maximum plasma drug concentration) and $T_{max}$ $(time\;to\;reach\;C_{max})$ were compiled from the plasma drug concentration-time data. Analysis of variance (ANOVA) revealed that there are no differences in AUC, $C_{max}$ and $T_{max}$ between the formulations. The apparent differences between the formulations in these parameters were all far less than 20% (i.e., 5.88, 7.81 and 6.09% for AUC, $C_{max}$ and $T_{max}$, respectively). Minimum detectable differences (%) at ${\alpha}=0.1$ and $1-{\beta}=0.8$ were all less than 20% difference in these parameters between the formulations were all over 0.8 (i.e., 15.81, 13.13 and 19.85 for AUC, $C_{max}$ and $T_{max}$, respectively). The 90% confidence intervals for these parameters were also within ${\pm}20%$ (i.e., $-16.52{\sim}4.77$, $-16.65{\sim}1,02$ and $-19.45{\sim}7.28%$ for AUC, $C_{max}$ and $T_{max}$, respectively). These results satisfy the bioequivalence criteria of the Korea Food and Drug Administration (KFDA) guidelines (No. 98-51). Therefore, these results indicate that the 2 formulations of loxoprofen are bioequivalent and, thus, may be prescribed interchangeably.

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Biodeodorization of Trimethylamine by Biofilter Packed with Waste Tire-Chips (폐타이어칩 충진형 바이오 필터에 의한 Trimethylamine 제거)

  • Park, Hun-Ju;Kim, Chang-Gyun
    • Journal of Korean Society of Environmental Engineers
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    • v.30 no.8
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    • pp.789-797
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    • 2008
  • This study was conducted to investigate removal characteristics of gaseous trimethylamine(TMA) through biofilter packed with waste tire-chips. The sludge in this experiment was collected from an activated sludge operated in a wastewater treatment facility treating malodorous pollutants. The nominal amount of collected sludge was inoculated through packing materials in the filter. The removal efficiencies for varying concentrations and SVs(Space velocity) were assessed based on TMA, COD$_{Cr}$, NO$_3{^-}$-N, NO$_2{^-}$-N, NH$_4{^+}$-N and EPS(Extracellular Polymeric Substances) in leachate, since biofilter had been steady-stately operated. The influent concentration of 10 ppm of TMA was removed to approximately 95% regardless of changing SV at 120 and 180 hr$^{-1}$, but it was lowered to 80 to 90% at SV 240 hr$^{-1}$. As influent concentration was gradually increased from 5 to 55 ppm, the removal efficiencies of TMA were initially high for 95% in the range of 5 to 10 ppm, but lowered to 80% for 10 to 30 ppm. As a part of kinetic study for TMA decomposition, V$_m$(maximum substrate removal rate) and $K_s$(substrate infinity coefficient) were 14.3 g$\cdot$m$^{-3}$$\cdot$h$^{-1}$ and 0.043 g$\cdot$m$^{-3}$, respectively while adapted period was shown in the range of 100 to 150 hr. Also, the EPS concentration was consistently observed from the leachate showing 100 to 200 ppm, which indicates that biofilm has been continuously formed and sustained throughout tire-chips packed reactor.