• Title/Summary/Keyword: Complex Mode Analysis

Search Result 361, Processing Time 0.027 seconds

Crystal Structures of Spleen Tyrosine Kinase in Complex with Two Novel 4-Aminopyrido[4,3-d] Pyrimidine Derivative Inhibitors

  • Lee, Sang Jae;Choi, Jang-Sik;Bong, Seoung Min;Hwang, Hae-Jun;Lee, Jaesang;Song, Ho-Juhn;Lee, Jaekyoo;Kim, Jung-Ho;Koh, Jong Sung;Lee, Byung Il
    • Molecules and Cells
    • /
    • v.41 no.6
    • /
    • pp.545-552
    • /
    • 2018
  • Spleen tyrosine kinase (SYK) is a cytosolic non-receptor protein tyrosine kinase. Because SYK mediates key receptor signaling pathways involving the B cell receptor and Fc receptors, SYK is an attractive target for autoimmune disease and cancer treatments. To date, representative oral SYK inhibitors, including fostamatinib (R406 or R788), entospletinib (GS-9973), cerdulatinib (PRT062070), and TAK-659, have been assessed in clinical trials. Here, we report the crystal structures of SYK in complex with two newly developed inhibitors possessing 4-aminopyrido[4,3-D]pyrimidine moieties (SKI-G-618 and SKI-O-85). One SYK inhibitor (SKI-G-618) exhibited moderate inhibitory activity against SYK, whereas the other inhibitor (SKI-O-85) exhibited a low inhibitory profile against SYK. Binding mode analysis indicates that a highly potent SYK inhibitor might be developed by modifying and optimizing the functional groups that interact with Leu377, Gly378, and Val385 in the G-loop and the nearby region in SYK. In agreement with our structural analysis, one of our SYK inhibitor (SKI-G-618) shows strong inhibitory activities on the ${\beta}$-hexosaminidase release and phosphorylation of SYK/Vav in RBL-2H3 cells. Taken together, our findings have important implications for the design of high affinity SYK inhibitors.

Analysis on the Filling Mode of Propellant Supply System for the Korea Space Launch Vehicle (한국형발사체 추진제공급시스템 충전모드 해석)

  • Lee, Jaejun;Park, Sangmin;Kang, Sunil;Oh, Hwayoung;Jung, Eun Sang
    • Journal of the Korean Society of Propulsion Engineers
    • /
    • v.20 no.4
    • /
    • pp.50-58
    • /
    • 2016
  • Korean Space Launch Vehicle (KSLV-II) Propellant Supply System charges liquid oxygen and kerosene to each propellant tank for the stages. To charge the launch vehicle propellant tank safety, the propellant charge flow rates and scenarios should be defined. First, the Propellant Supply System was modeled with 1D flow analysis program. The control valve capacity and orifice size were calculated by performing the 1D steady state simulation. Second, the 1D transient simulation was performed by using the steady state simulation results. As propellants were being charged at the each tank, the increased tank liquid level decreases the charge flow rate. Consequently, the proposed supply system satisfies the required design charging conditions.

Design of Sliding Mode Fuzzy Controller for Vibration Reduction of Large Structures (대형구조물의 진동 감소를 위한 슬라이딩 모드 퍼지 제어기의 설계)

  • 윤정방;김상범
    • Journal of the Earthquake Engineering Society of Korea
    • /
    • v.3 no.3
    • /
    • pp.63-74
    • /
    • 1999
  • A sliding mode fuzzy control (SMFC) algorithm is presented for vibration of large structures. Rule-base of the fuzzy inference engine is constructed based on the sliding mode control, which is one of the nonlinear control algorithms. Fuzziness of the controller makes the control system robust against the uncertainties in the system parameters and the input excitation. Non-linearity of the control rule makes the controller more effective than linear controllers. Design procedure based on the present fuzzy control is more convenient than those of the conventional algorithms based on complex mathematical analysis, such as linear quadratic regulator and sliding mode control(SMC). Robustness of presented controller is illustrated by examining the loop transfer function. For verification of the present algorithm, a numerical study is carried out on the benchmark problem initiated by the ASCE Committee on Structural Control. To achieve a high level of realism, various aspects are considered such as actuator-structure interaction, modeling error, sensor noise, actuator time delay, precision of the A/D and D/A converters, magnitude of control force, and order of control model. Performance of the SMFC is examined in comparison with those of other control algorithms such as $H_{mixed 2/{\infty}}$ optimal polynomial control, neural networks control, and SMC, which were reported by other researchers. The results indicate that the present SMFC is an efficient and attractive control method, since the vibration responses of the structure can be reduced very effectively and the design procedure is simple and convenient.

  • PDF

Cobalt(II) Complex of 1,2-Bis(2,2'-bipyridyl-6-yl)ethane. Crystallization Process and Structural Analysis of Two Shapes of Crystals (1,2-비스(2,2'-디피리딜-6일)에탄의 코발트 착물. 두 가지 형태의 결정화 과정 및 구조 분석적 접근)

  • Park, Sung-Ho;Yoo, Kyung-Ho;Jung, Ok-Sang
    • Analytical Science and Technology
    • /
    • v.12 no.5
    • /
    • pp.421-427
    • /
    • 1999
  • Two shapes of crystals have been isolated by the interdiffusion of $Co(NCS)_2$ dissolved in methanol with 1,2-bis(2,2'-bipyridyl-6-yl)ethane (bbpe) dissolved in chloroform. The two crystals have been elucidated as $trans-Co^{II}(NCS)_2(bbpe)$ and $trans-Co^{II}(NCS)_2(bbpe){\cdot}2CHCl_3$, by X-ray crystallography, elemental analysis, IR, and thermal analysis. The two molecular structures are very similar except for the absence or presence of chloroform solvate molecules. The bbpe ligand coordinates to the cobalt(II) ion in an open-ended tetradentate mode, resulting in discrete mononuclear cobalt(II) complex. The cobalt atom adopts a typical octahedral arrangement with six nitrogen donating atoms with two NCS groups in trans positions. A significant solid-to-solid phase transition occurs presumably due to the change of conformationally flexible bbpe ligand. The formation of both crystals oeeurs in a successive two-step process, the formation of $trans-Co^{II}(NCS)_2(bbpe)$ and its transformation into $trans-Co^{II}(NCS)_2(bbpe){\cdot}2CHCl_3$. The thermal stability and favorable formation of the solvate crystals may be ascribed to the interaction between S atom of NCS group and Cl of chloroform.

  • PDF

Non-Essential Activation of Co2+ and Zn2+ on Mushroom Tyrosinase: Kinetic and Structural Stability

  • Gheibi, N.;Saboury, A.A.;Sarreshtehdari, M.
    • Bulletin of the Korean Chemical Society
    • /
    • v.32 no.5
    • /
    • pp.1500-1506
    • /
    • 2011
  • Tyrosinase is a widespread enzyme with great promising capabilities. The Lineweaver-Burk plots of the catecholase reactions showed that the kinetics of mushroom tyrosinase (MT), activated by $Co^{2+}$ and $Zn^{2+}$ at different pHs (6, 7, 8 and 9) obeyed the non-essential activation mode. The binding of metal ions to the enzyme increases the maximum velocity of the enzyme due to an increase in the enzyme catalytic constant ($k_{cat}$). From the kinetic analysis, dissociation constants of the activator from the enzyme-metal ion complex ($K_a$) were obtained as $5{\times}10^4M^{-1}$ and $8.33{\times}10^3M^{-1}$ for $Co^{2+}$ and $Zn^{2+}$ at pH 9 and 6 respectively. The structural analysis of MT through circular dichroism (CD) and intensive fluorescence spectra revealed that the conformational stability of the enzyme in these pHs reaches its maximum value in the presence of each of the two metal ions.

A Design Fitness Analysis of Journal Bearings for LPLi Fuel Pump Application (LPLi 연료펌프 적용을 위한 저어널 베어링의 설계 적합성 해석)

  • Lee, An-Sung;Kim, Chang-Up
    • Tribology and Lubricants
    • /
    • v.25 no.5
    • /
    • pp.324-329
    • /
    • 2009
  • In this study a complex design fitness analysis of journal bearings is carried out for the LPLi rotary-vane fuel pump application, as an external and horizontal installation, in LPG vehicles. Bearings considered in the analyses are plain and 3-axial groove journal bearings. Upon reflecting the fact that the primary failure mode of bearings in the application is a premature friction and wear failure of bearing metal due to a very low viscosity of liquid fuel LPG as a bearing lubricant, the performance factors of bearings used in an evaluation process of design fitness are a load carrying capacity and vibration suppression ability relative to a rated speed. At this time the design variables of bearings are a radial clearance and length. Results show that, in terms of both of the load carrying capacity and vibration suppression ability, the plain journal bearings are superior to the 3-axial groove journal bearings and among the plain bearings the smaller the bearing clearance (5>10>$15\;{\mu}m$) is and the longer the bearing length (6<8<10<12<14 mm) is, the better the bearing performance is.

Analysis of th estress intensity factor of mode I crack in a finite width plate with variable thickness (두께가 變化하는 有限幅板材에서의 모우드 I 龜裂 應力擴大係數 解析)

  • 양원호;방시항
    • Transactions of the Korean Society of Mechanical Engineers
    • /
    • v.11 no.1
    • /
    • pp.132-144
    • /
    • 1987
  • This paper presents the theroetical analysis of the crack tip stress intensity factor for a center crack in a finite width plate with variable thickness. The analyses were based on Laurent's expansions of complex stress potentials where the expansion coefficients are determined from the boundary conditions. The perturbation method was employed in numerical calculations. The correction factor F(.lambda.)is given in the form of power series of .lambda. [a numerical formula] where .lambda.=a/w$^{1}$; Dimensionless crack length, .betha.=t$_{2}$/t; Thickness ratio .omega.=w$_{2}$/w$_{1}$; width ratio The correction factor values vary with the width ratio .omega. and the maximum variation occurs around .betha.=1. For the case of .betha.=1 or .betha.=0 (uniform thickness plate0, the correction factor values agree well with Feddersen's formula. In all cases, as .lambda. approaches to 1 (thickness interface), the correction factor values are decreased rapidly for .betha.>1, and increased rapidly for .betha.<1.

Development of Optimal Design User Interface for Waveguide tee Junction using PSO Algorithm and VBA (PSO 알고리즘과 VBA를 이용한 Waveguide tee Junction의 최적설계 인터페이스 개발)

  • Park, Hyun-Soo;Byun, Jin-Kyu;Lee, Dal-Ho;Lee, Hyang-Beom
    • 한국정보통신설비학회:학술대회논문집
    • /
    • 2009.08a
    • /
    • pp.36-39
    • /
    • 2009
  • We developed an optimal design interface based on VBA(Visual Basic Application) that takes advantage of API(Application Program Interface) function of commonly used EM analysis software. The developed interface is adopted for an optimal design of a septum in a waveguide tee junction using PSO(Particle Swarm Optimization) algorithm. The objective function of the optimal design is defined by $S_{11}$-parameter of the waveguide tee junction Design variables are established as position of the septum, that are changed to satisfy the design goal Using the developed design interface and PSO algorithm, the objective function converged to the smallest value, showing the validity of the proposed method. The design interface was developed using Microsoft Excel software, enabling easy control of design parameters for user. Also, various analysis parameters can be set in the Excel interface, including waveguide input mode and frequency. After completion of the design, field solutions at user-specified positrons can be extracted to the output files in complex number form.

  • PDF

Numerically integrated modified virtual crack closure integral technique for 2-D crack problems

  • Palani, G.S.;Dattaguru, B.;Iyer, Nagesh R.
    • Structural Engineering and Mechanics
    • /
    • v.18 no.6
    • /
    • pp.731-744
    • /
    • 2004
  • Modified virtual crack closure integral (MVCCI) technique has become very popular for computation of strain energy release rate (SERR) and stress intensity factor (SIF) for 2-D crack problems. The objective of this paper is to propose a numerical integration procedure for MVCCI so as to generalize the technique and make its application much wider. This new procedure called as numerically integrated MVCCI (NI-MVCCI) will remove the dependence of MVCCI equations on the type of finite element employed in the basic stress analysis. Numerical studies on fracture analysis of 2-D crack (mode I and II) problems have been conducted by employing 4-noded, 8-noded (regular & quarter-point), 9-noded and 12-noded finite elements. For non-singular (regular) elements at crack tip, NI-MVCCI technique generates the same results as MVCCI, but the advantage for higher order regular and singular elements is that complex equations for MVCCI need not be derived. Gauss numerical integration rule to be employed for 8-noded singular (quarter-point) element for accurate computation of SERR and SIF has been recommended based on the numerical studies.

Wear Characteristics of Multi- span Tube Due to Turbulence Excitation (다경간 전열관의 난류 가진에 의한 마모특성 연구)

  • Kim, Hyung-Jin;Sung, Bong-Zoo;Park, Chi-Yong;Ryu, Ki-Whan
    • Transactions of the Korean Society for Noise and Vibration Engineering
    • /
    • v.16 no.9 s.114
    • /
    • pp.904-911
    • /
    • 2006
  • A modified energy method for the fretting wear of the steam generator tube is proposed to calculate the wear-out depth between the nuclear steam generator tube and its support. Estimation of fretting-wear damage typically requires a non-linear dynamic analysis with the information of the gap velocity and the flow density around the tube. This analysis is very complex and time consuming. The basic concept of the energy method is that the volume wear rate due to the fretting-wear phenomena Is related to work rate which is time rate of the product of normal contact force and sliding distance. The wearing motion is due to dynamic interaction between vibrating tube and its support structure, such as tube support plate and anti-vibration bar. It can be assumed that the absorbed work rate would come from turbulent flow energy around the vibrating tube. This study also numerically obtains the wear-out depth with various wear topologies. A new dissection method is applied to the multi-span tubes to represent the vibrational mode. It turns out that both the secondary side density and the normal gap velocity are important parameters for the fretting-wear phenomena of the steam generator tube.