The spectrum of clinical efficacy of Methotrexate (MTX) is broad in that MTX is used in the treatment of certain cancers, severe psoriasis and rheumatoid arthritis.Various mechanisms by which cancer cells grown in tissue culture become resistant to anticancer drugs. The use of multiple drugs with different mechanisms of entry into cells and different cellular targets allows for effective chemotherapy and high cure rates. In an efforts to develop effective strategies that increase the therapeutic potential of anticancer drugs with less systemic toxicity ,are being directed towards the investigation of dietary supplements and other phytotherapeutic agents for their synergistic efficacy in combination with anticancer drugs. A promising approach to improve the cancer cell selectivity of methotrexate is the chemical transformation into reversible derivatives which convert the conjugate to the parent drug by virtue of enzyme within cancer tissue. The present study includes the synthesis of two derivatives of methotrexate which are :-Schiff base methotrexate-silibinin conjugate ( compound 5), and Methotrexate-silibinin conjugate (compound 6).The synthesis of the target compounds was accomplished following multistep reaction procedures. The chemical reactions were followed up and purity of the products was checked by TLC. The structures of the final compounds and their intermediates were characterized and identified by their melting points, infrared spectroscopy, 1H-NMR and elemental microanalysis(C H N S).The anticancer activity of these compounds was investigated by HEP-2 cell line(Larynx carcinoma), which showed that compounds 5 and 6 have the higher activity than methotrexate or silibinin alone.These are promising data for the discovery of new anticancer agents in future. These compounds may deliver the parent drug selectively into the cancer cells to be hydrolyzed by enzymes that are elevated in tumor tissues compared with normal tissues . Keywords: Methotrexate, Silibinin, Cancer treatment resistance, Folate receptor, Cancer cell targeting.
In this paper, an Integral Backstepping Controller (IBC) is designed and optimized for full control, of rotational and translational dynamics, of an unmanned Quadcopter (QC). Before designing the controller, a mathematical model for the QC is developed in a form appropriate for the IBC design. Due to the underactuated property of the QC, it is possible to control the QC Cartesian positions (X, Y, and Z) and the yaw angle through ordering the desired values for them. As for the pitch and roll angles, they are generated by the position controllers. Backstepping Controller (BC) is a practical nonlinear control scheme based on Lyapunov design approach, which can, therefore, guarantee the convergence of the position tracking
... Show MoreA computational investigation has been carried out on the design and properties of the electrostatic mirror. In this research, we suggest a mathematical expression to represent the axial potential of an electrostatic mirror. The electron beam path under zero magnification condition had been investigated as mirror trajectory with the aid of fourth – order – Runge – Kutta method. The spherical and chromatic aberration coefficients of mirror has computed and normalized in terms of the focal length. The choice of the mirror depends on the operational requirements, i.e. each optical element in optical system has suffer from the chromatic aberration, for this case, it is use to operate the mirror in optical system at various values
... Show MoreThe goal of this paper is to design a robust controller for controlling a pendulum
system. The control of nonlinear systems is a common problem that is facing the researchers in control systems design. The Sliding Mode Controller (SMC) is the best solution for controlling a nonlinear system. The classical SMC consists from two phases. The first phase is the reaching phase and the second is the sliding phase. The SMC suffers from the chattering phenomenon which is considered as a severe problem and undesirable property. It is a zigzag motion along the switching surface. In this paper, the chattering is reduced by using a saturation function instead of sign function. In spite of SMC is a good method for controlling a nonlinear system b
The process of controlling a Flexible Joint Robot Manipulator (FJRM) requires additional sensors for measuring the state variables of flexible joints. Therefore, taking the elasticity into account adds a lot of complexity as all the additional sensors must be taken into account during the control process. This paper proposes a nonlinear observer that controls FJRM, without requiring equipment sensors for measuring the states. The nonlinear state equations are derived in detail for the FJRM where nonlinearity, of order three, is considered. The Takagi–Sugeno Fuzzy Model (T-SFM) technique is applied to linearize the FJRM system. The Luenberger observer is designed to estimate the unmeasured states using error correction. The develop
... Show MoreArabic calligraphy has great importance in the printing designs that are often on the written character-based to perform functional goals and to achieve some of the aesthetic values in design work, has led major developments in the field of computer manufacturing and design software for the design and layout to increase to deal with the programmed character for the purposes of typesetting has confronted this Find the Arab character programmed for the purposes of typesetting for the detection of the most important design interventions that underwent the Arabic letter written to turn it into a programmed image intended for the purposes of the printing and typesetting has been addressed in the context of which the theoretical types of
... Show MoreL1 adaptive controller has proven to provide fast adaptation with guaranteed transients in a large variety of systems. It is commonly used for controlling systems with uncertain time-varying unknown parameters. The effectiveness of L1 adaptive controller for position control of single axis has been examined and compared with Model Reference Adaptive Controller (MRAC). The Linear servo motor is one of the main constituting elements of the x-y table which is mostly used in automation application. It is characterized by time-varying friction and disturbance.
The tracking and steady state performances of both controllers have been assessed fo
... Show MoreAbstract
One of the major components in an automobile engine is the throttle valve part. It is used to keep up with emissions and fuel efficiency low. Design a control system to the throttle valve is newly common requirement trend in automotive technology. The non-smoothness nonlinearity in throttle valve model are due to the friction model and the nonlinear spring, the uncertainty in system parameters and non-satisfying the matching condition are the main obstacles when designing a throttle plate controller.
In this work, the theory of the Integral Sliding Mode Control (ISMC) is utilized to design a robust controller for the Electronic Throttle Valve (ETV) system. From the first in
... Show MoreIn this paper, first and second order sliding mode controllers are designed for a single link robotic arm actuated by two Pneumatic Artificial Muscles (PAMs). A new mathematical model for the arm has been developed based on the model of large scale pneumatic muscle actuator model. Uncertainty in parameters has been presented and tested for the two controllers. The simulation results of the second-order sliding mode controller proves to have a low tracking error and chattering effect as compared to the first order one. The verification has been done by using MATLAB and Simulink software.