A TSG101/MDM2 regulatory loop modulates MDM2 degradation and MDM2/p53 feedback control

The p53 tumor suppressor protein and the MDM2 oncoprotein form a feedback-control loop that up-regulates cellular MDM2 production, blocks p53 activity, and promotes p53 decay. tsg101 was discovered as a gene whose deficiency results in neoplastic transformation of NIH 3T3 cells and the ability to generate metastatic tumors in nude mice. Its protein product contains a domain, Ubc, characteristic of the catalytic domain of ubiquitin conjugase (E2) enzymes but lacking an active-site cysteine crucial for ubiquitin conjugase activity. Here we report that TSG101 participates with MDM2 in an autoregulatory loop that modulates the cellular levels of both proteins, and also of p53, by affecting protein decay. We show that the Ubc domain of TSG101 interferes with ubiquitination of MDM2, that TSG101 inhibits MDM2 decay and elevates its steady-state level, and that these events are associated with down-regulation of p53 protein. Conversely, pulse–chase and Western blot experiments in wild-type and mutant fibroblasts indicate that elevation of MDM2 by overexpression of wild-type p53, by amplification of the endogenous MDM2 gene, or by transfection of MDM2-expressing constructs promotes TSG101 loss, which we show occurs by 26S proteasome-dependent decay. Our results identify TSG101 as both a regulator of, and target of, MDM2/p53 circuitry.

Feedback control of underactuated cable-driven parallel robots

In this work an Underactuated Cable-Driven Parallel Robot (UACDPR) that operates in the three dimensional Euclidean space is considered. The End-Effector has 6 degrees of freedom and is actuated by 4 cables, therefore from a mechanical point of view the robot is defined underconstrained. However, considering only three controlled pose variables, the degree of redundancy for the control theory can be considered one. The aim of this thesis is to design a feedback controller for a point-to-point motion that satisfies the transient requirements, and is capable of reducing oscillations that derive from the reduced number of constraints. A force control is chosen for the positioning of the End-Effector, and error with respect to the reference is computed through data measure of several sensors (load cells, encoders and inclinometers) such as cable lengths, tension and orientation of the platform. In order to express the relation between pose and cable tension, the inverse model is derived from the kinematic and dynamic model of the parallel robot. The intrinsic non-linear nature of UACDPRs systems introduces an additional level of complexity in the development of the controller, as a result the control law is composed by a partial feedback linearization, and damping injection to reduce orientation instability. The fourth cable allows to satisfy a further tension distribution constraint, ensuring positive tension during all the instants of motion. Then simulations with different initial conditions are presented in order to optimize control parameters, and lastly an experimental validation of the model is carried out, the results are analysed and limits of the presented approach are defined.

A state-space modeling approach for active structural acoustic control

The demands for improvement in sound quality and reduction of noise generated by vehicles are constantly increasing, as well as the penalties for space and weight of the control solutions. A promising approach to cope with this challenge is the use of active structural-acoustic control. Usually, the low frequency noise is transmitted into the vehicle`s cabin through structural paths, which raises the necessity of dealing with vibro-acoustic models. This kind of models should allow the inclusion of sensors and actuators models, if accurate performance indexes are to be accessed. The challenge thus resides in deriving reasonable sized models that integrate structural, acoustic, electrical components and the controller algorithm. The advantages of adequate active control simulation strategies relies on the cost and time reduction in the development phase. Therefore, the aim of this paper is to present a methodology for simulating vibro-acoustic systems including this coupled model in a closed loop control simulation framework that also takes into account the interaction between the system and the control sensors/actuators. It is shown that neglecting the sensor/actuator dynamics can lead to inaccurate performance predictions.

Experimental analysis of active-passive vibration control using viscoelastic materials and extension and shear piezoelectric actuators

Hybrid active-passive damping treatments combine the reliability, low cost and robustness of viscoelastic damping treatments and the high-performance, modal selective and adaptive piezoelectric active control. Numerous hybrid damping treatments have been reported in the literature. They differ mainly by the relative positions of viscoelastic treatments, sensors and piezoelectric actuators. In this work we present an experimental analysis of three active-passive damping design configurations applied to a cantilever beam. In particular, two design configurations based on the extension mode of piezoelectric actuators combined with viscoelastic constrained layer damping treatments and one design configuration with shear piezoelectric actuators embedded in a sandwich beam with viscoelastic core are analyzed. For comparison purposes, a purely active design configuration with an extension piezoelectric actuator bonded to an elastic beam is also analyzed. The active-passive damping performance of the four design configurations is compared. Results show that active-passive design configurations provide more reliable and wider-range damping performance than the purely active configuration.

Active magneto-optical control of spontaneous emission in graphene

We investigate the spontaneous emission rate of a two-level quantum emitter near a graphene-coated substrate under the influence of an external magnetic field or strain induced pseudo-magnetic field. We demonstrate that the application of the magnetic field can substantially increase or decrease the decay rate. We show that a suppression as large as 99$\%$ in the Purcell factor is achieved even for moderate magnetic fields. The emitter's lifetime is a discontinuous function of $|{\bf B}|$, which is a direct consequence of the occurrence of discrete Landau levels in graphene. We demonstrate that, in the near-field regime, the magnetic field enables an unprecedented control of the decay pathways into which the photon/polariton can be emitted. Our findings strongly suggest that a magnetic field could act as an efficient agent for on-demand, active control of light-matter interactions in graphene at the quantum level.

Optimal feedback control rules sensitive to controlled endogenous risk-aversion

The objective of this paper is to correct and improve the results obtained by Van der Ploeg (1984a, 1984b) and utilized in the theoretical literature related to feedback stochastic optimal control sensitive to constant exogenous risk-aversion (see, Jacobson, 1973, Karp, 1987 and Whittle, 1981, 1989, 1990, among others) or to the classic context of risk-neutral decision-makers (see, Chow, 1973, 1976a, 1976b, 1977, 1978, 1981, 1993). More realistic and attractive, this new approach is placed in the context of a time-varying endogenous risk-aversion which is under the control of the decision-maker. It has strong qualitative implications on the agent's optimal policy during the entire planning horizon.

Feedback control of DnaA-mediated replication initiation by replisome-associated HdaA protein in Caulobacter.

Chromosome replication in Caulobacter crescentus is tightly regulated to ensure that initiation occurs at the right time and only once during the cell cycle. The timing of replication initiation is controlled by both CtrA and DnaA. CtrA binds to and silences the origin. Upon the clearance of CtrA from the cell, the DnaA protein accumulates and allows loading of the replisome at the origin. Here, we identify an additional layer of replication initiation control that is mediated by the HdaA protein. In Escherichia coli, the Hda protein inactivates DnaA after replication initiation. We show that the Caulobacter HdaA homologue is necessary to restrict the initiation of DNA replication to only once per cell cycle and that it dynamically colocalizes with the replisome throughout the cell cycle. Moreover, the transcription of hdaA is directly activated by DnaA, providing a robust feedback regulatory mechanism that adjusts the levels of HdaA to inactivate DnaA.

Feedback control of unstable cellular solidification fronts

We present a feedback control scheme to stabilize unstable cellular patterns during the directional solidification of a binary alloy. The scheme is based on local heating of cell tips which protrude ahead of the mean position of all tips in the array. The feasibility of this scheme is demonstrated using phase-field simulations and, experimentally, using a real-time image processing algorithm, to track cell tips, coupled with a movable laser spot array device to heat the tips locally. We demonstrate, both numerically and experimentally, that spacings well below the threshold for a period-doubling instability can be stabilized. As predicted by the numerical calculations, cellular arrays become stable with uniform spacing through the feedback control which is maintained with minimal heating.

Analysis of Active Magnet Bearing Control Software

Problems of the designing active magnet bearingcontrol are developed. The estimation controller are designed and applied to a rigid rotor. The mathematical model of the active magnet bearing controller is developed. This mathematical model is realized on a DSP. The results of this realization are analyzed. The conclusions about the digital signal processing are made.

Bifurcation Analysis of Eigenstructure Assignment Control in a Simple Nonlinear Aircraft Model

Aircraft systems are highly nonlinear and time varying. High-performance aircraft at high angles of incidence experience undesired coupling of the lateral and longitudinal variables, resulting in departure from normal controlled � ight. The construction of a robust closed-loop control that extends the stable and decoupled � ight envelope as far as possible is pursued. For the study of these systems, nonlinear analysis methods are needed. Previously, bifurcation techniques have been used mainly to analyze open-loop nonlinear aircraft models and to investigate control effects on dynamic behavior. Linear feedback control designs constructed by eigenstructure assignment methods at a � xed � ight condition are investigated for a simple nonlinear aircraft model. Bifurcation analysis, in conjunction with linear control design methods, is shown to aid control law design for the nonlinear system.