• Title/Summary/Keyword: translational control

Search Result 271, Processing Time 0.038 seconds

A small molecule approach to degrade RAS with EGFR repression is a potential therapy for KRAS mutation-driven colorectal cancer resistance to cetuximab

  • Lee, Sang-Kyu;Cho, Yong-Hee;Cha, Pu-Hyeon;Yoon, Jeong-Soo;Ro, Eun Ji;Jeong, Woo-Jeong;Park, Jieun;Kim, Hyuntae;Kim, Tae Il;Min, Do Sik;Han, Gyoonhee;Choi, Kang-Yell
    • Experimental and Molecular Medicine
    • /
    • v.50 no.11
    • /
    • pp.12.1-12.12
    • /
    • 2018
  • Drugs targeting the epidermal growth factor receptor (EGFR), such as cetuximab and panitumumab, have been prescribed for metastatic colorectal cancer (CRC), but patients harboring KRAS mutations are insensitive to them and do not have an alternative drug to overcome the problem. The levels of ${\beta}$-catenin, EGFR, and RAS, especially mutant KRAS, are increased in CRC patient tissues due to mutations of adenomatous polyposis coli (APC), which occur in 90% of human CRCs. The increases in these proteins by APC loss synergistically promote tumorigenesis. Therefore, we tested KYA1797K, a recently identified small molecule that degrades both ${\beta}$-catenin and Ras via $GSK3{\beta}$ activation, and its capability to suppress the cetuximab resistance of KRAS-mutated CRC cells. KYA1797K suppressed the growth of tumor xenografts induced by CRC cells as well as tumor organoids derived from CRC patients having both APC and KRAS mutations. Lowering the levels of both ${\beta}$-catenin and RAS as well as EGFR via targeting the $Wnt/{\beta}$-catenin pathway is a therapeutic strategy for controlling CRC and other types of cancer with aberrantly activated the $Wnt/{\beta}$-catenin and EGFR-RAS pathways, including those with resistance to EGFR-targeting drugs attributed to KRAS mutations.

Regulation of Macrophage Ceruloplasmin Gene Expression: One Paradigm of 3'-UTR-mediated Translational Control

  • Mazumder, Barsanjit;Sampath, Prabha;Fox, Paul L.
    • Molecules and Cells
    • /
    • v.20 no.2
    • /
    • pp.167-172
    • /
    • 2005
  • Ceruloplasmin (Cp) is a copper protein with important functions in iron homeostasis and in inflammation. Cp mRNA expression is induced by interferon (IFN)-${\gamma}$ in U937 monocytic cells, but synthesis of Cp protein is halted after about 12 h by transcript-specific translational silencing. The silencing mechanism requires binding of a 4-component cytosolic inhibitor complex, IFN-gamma-activated inhibitor of translation (GAIT), to a defined structural element (GAIT element) in the Cp 3'-UTR. Translational silencing of Cp mRNA requires the essential proteins of mRNA circularization, suggesting that the translational inhibition requires end-to-end mRNA closure. These studies describe a new mechanism of translational control, and may shed light on the role that macrophage-derived Cp plays at the intersection of iron homeostasis and inflammation.

Translational control of a one link flexible arm

  • Lee, Seong-Cheol;Seiji Chonan;Hikaru Inooka
    • 제어로봇시스템학회:학술대회논문집
    • /
    • 1989.10a
    • /
    • pp.577-582
    • /
    • 1989
  • This is a study of the translational end-point control of a single link flexible arm-with a tip mass. The beam is mounted on a translational mechanism driven by the ball screw, whose rotation is controlled by DC servomotor. The problem of shifting the end-point from its initial position to the commanded position is studied analytically both for the open-loop control subjected to some path functions and for the closed-loop control using the feedback of the tip information.

  • PDF

A Study on Translational Motion Control in Integrated Control System for Ship Steering Motion (선박 조종운동을 위한 통합제어시스템에서의 이동운동제어에 관한 연구)

  • Woo, Ju-Eun;Kim, Jong-Hwa
    • Journal of Advanced Marine Engineering and Technology
    • /
    • v.39 no.1
    • /
    • pp.32-44
    • /
    • 2015
  • In general, a series of ship steering motion is represented by the combination of translational motion and rotational motion of the ship. Especially, special-functioned ships such as large-scale cruises, ships for installing underwater optical cable, and diver ships must be able to reveal only a translational motion without the change of orientation. In this paper, a method to comprise an integrated control system based on the joystick as a command instrument for translational motion control is suggested. In order to realize the translational motion control system, several algorithms are suggested including the velocity command generation, the selection of motional variables, and the generation and tracking of reference inputs for the selected motional variables. A simulation bench is composed to execute simulations for several translational motion commands. At last, the effectiveness of the proposed method is verified by analyzing the simulation results.

Identification and Robust $H_\infty$ Control of the Rotational/Translational Actuator System

  • Tavakoli Mahdi;Taghirad Hamid D.;Abrishamchian Mehdi
    • International Journal of Control, Automation, and Systems
    • /
    • v.3 no.3
    • /
    • pp.387-396
    • /
    • 2005
  • The Rotational/Translational Actuator (RTAC) benchmark problem considers a fourth-order dynamical system involving the nonlinear interaction of a translational oscillator and an eccentric rotational proof mass. This problem has been posed to investigate the utility of a rotational actuator for stabilizing translational motion. In order to experimentally implement any of the model-based controllers proposed in the literature, the values of model parameters are required which are generally difficult to determine rigorously. In this paper, an approach to the least-squares estimation of the parameters of a system is formulated and practically applied to the RTAC system. On the other hand, this paper shows how to model a nonlinear system as a linear uncertain system via nonparametric system identification, in order to provide the information required for linear robust $H_\infty$ control design. This method is also applied to the RTAC system, which demonstrates severe nonlinearities, due to the coupling from the rotational motion to the translational motion. Experimental results confirm that this approach can effectively condense the whole nonlinearities, uncertainties, and disturbances within the system into a favorable perturbation block.

APPLICATION OF INVERSE DUNAMICS FOR HYBRID TRANSLATIONAL POSITION/FORCE CONTROL OF A FLEXIBLE ROBOT ARM

  • Sasaki, Minoru;Inooka, Hikaru
    • 제어로봇시스템학회:학술대회논문집
    • /
    • 1989.10a
    • /
    • pp.595-599
    • /
    • 1989
  • A new simple method for controlling compliant motions of a flexible robot arm is presented. The method aims at controlling translational tip motion, force and moment by directly computing the base motion or torque. A numerical inversion of Laplace transform is used to obtain the results in the time domain. The results show the effectiveness of the method for the hybrid translational position/force control of a flexible robot arm.

  • PDF

Estimation of active multiple tuned mass dampers for asymmetric structures

  • Li, Chunxiang;Xiong, Xueyu
    • Structural Engineering and Mechanics
    • /
    • v.29 no.5
    • /
    • pp.505-530
    • /
    • 2008
  • This paper proposes the application of active multiple tuned mass dampers (AMTMD) for translational and torsional response control of a simplified two-degree-of-freedom (2DOF) structure, able to represent the dynamic characteristics of general asymmetric structures, under the ground acceleration. This 2DOF structure is a generalized 2DOF system of an asymmetric structure with predominant translational and torsional responses under earthquake excitations using the mode reduced-order method. Depending on the ratio of the torsional to the translational eigenfrequency, i.e. the torsional to translational frequency ratio (TTFR), of asymmetric structures, the following three cases can be distinguished: (1) torsionally flexible structures (TTFR < 1.0), (2) torsionally intermediate stiff structures (TTFR = 1.0), and (3) torsionally stiff structures (TTFR > 1.0). The even distribution of the AMTMD within the whole width and half width of the asymmetric structure, thus leading to three cases of installing the AMTMD (referred to as the AMTMD of case 1, AMTMD of case 2, AMTMD of case 3, respectively), is taken into account. In the present study, the criterion for searching the optimum parameters of the AMTMD is defined as the minimization of the minimum values of the maximum translational and torsional displacement dynamic magnification factors (DMF) of an asymmetric structure with the AMTMD. The criterion used for assessing the effectiveness of the AMTMD is selected as the ratio of the minimization of the minimum values of the maximum translational and torsional displacement DMF of the asymmetric structure with the AMTMD to the maximum translational and torsional displacement DMF of the asymmetric structure without the AMTMD. By resorting to these two criteria, a careful examination of the effects of the normalized eccentricity ratio (NER) on the effectiveness and robustness of the AMTMD are carried out in the mitigation of both the translational and torsional responses of the asymmetric structure. Likewise, the effectiveness of a single ATMD with the optimum positions is presented and compared with that of the AMTMD.

A Forward Closed-Form Position Solution, Kinematic Analysis And Implementation of a Translational 3-DOF Parallel Mechanism Formed by Constraining a Stewart Platform Structure (스트워트 플랫폼 구조를 구속하여 얻어지는 병진형 3 자유도 병렬 메커니즘의 정위치 해석해와 기구학 해석 및 구현)

  • Shin Dong-Min;Chung Jae-Heon;Oh Se-Min;Yi Byung-Ju;Kim Whee-Kuk
    • Journal of Institute of Control, Robotics and Systems
    • /
    • v.12 no.10
    • /
    • pp.1035-1043
    • /
    • 2006
  • In this study, a translational 3-DOF parallel mechanism formed by constraining the Stewart Platform Mechanism is investigated. The translational 3-DOF parallel mechanism has three struts(3-UPS type serial subchains) and in addition, has a PPP type serial subchain in the middle of the mechanism. Firstly, the closed-form forward and reverse position solutions are derived for this mechanism. And analysis on kinematic characteristics using isotropic index of the Jacobian is conducted to examine effects of design parameters for the mechanism. Lastly, a prototype mechanism is implemented and the kinematic performance of the translational 3-DOF parallel mechanism was verified through experimental work.

Physicians' Requirement Analysis Based Design of the Master Device Mechanism for Teleoperated Interventional Robotic System (원격 중재시술용 마스터장치에 대한 의료진 요구분석 및 이를 반영한 메커니즘 설계)

  • Woo, Hyun Soo;Cho, Jang Ho;Lee, Hyuk Jin
    • Journal of Institute of Control, Robotics and Systems
    • /
    • v.22 no.8
    • /
    • pp.603-609
    • /
    • 2016
  • This paper presents an optimally designed master device mechanism for teleoperated interventional robotic system. The interventional procedures using the teleoperated robotic system and the physicians' requirements are summarized. The master device should implement 5-DOF motion including 2-DOF translational motion for the entry position control, 2-DOF rotational motion for the orientation control, and 1- DOF translational motion for needle insertion. The handle assembly includes a 1-DOF translational mechanism for needle insertion and buttons for operation mode selection. The mechanisms for the 2-DOF translational motion and the 2-DOF rotational motion are designed using motors and brakes based on the various mechanisms to satisfy all the above requirements, respectively. Absolute position sensors are adopted to implement automatic initial positioning and orientation matching at the first step of needle insertion.

Altered Translational Control of Fragile X Mental Retardation Protein on Myelin Proteins in Neuropsychiatric Disorders

  • Jeon, Se Jin;Ryu, Jong Hoon;Bahn, Geon Ho
    • Biomolecules & Therapeutics
    • /
    • v.25 no.3
    • /
    • pp.231-238
    • /
    • 2017
  • Myelin is a specialized structure of the nervous system that both enhances electrical conductance and insulates neurons from external risk factors. In the central nervous system, polarized oligodendrocytes form myelin by wrapping processes in a spiral pattern around neuronal axons through myelin-related gene regulation. Since these events occur at a distance from the cell body, post-transcriptional control of gene expression has strategic advantage to fine-tune the overall regulation of protein contents in situ. Therefore, many research interests have been focused to identify RNA binding proteins and their regulatory mechanism in myelinating compartments. Fragile X mental retardation protein (FMRP) is one such RNA binding protein, regulating its target expression by translational control. Although the majority of works on FMRP have been performed in neurons, it is also found in the developing or mature glial cells including oligodendrocytes, where its function is not well understood. Here, we will review evidences suggesting abnormal translational regulation of myelin proteins with accompanying white matter problem and neurological deficits in fragile X syndrome, which can have wider mechanistic and pathological implication in many other neurological and psychiatric disorders.