Effective drug dosage design for treatment of infectious diseases using dynamic inversion

A generic nonlinear mathematical model describing the human immunological dynamics is used to design an effective automatic drug administration scheme. Even though the model describes the effects of various drugs on the dynamic system, this work is confined to the drugs that kill the invading pathogen and heal the affected organ. From a system theoretic point of view, the drug inputs can be interpreted as control inputs, which can be designed based on control theoretic concepts. The controller is designed based on the principle of dynamic inversion and is found to be effective in curing the �nominal model patient� by killing the invading microbes and healing the damaged organ. A major advantage of this technique is that it leads to a closed-form state feedback form of control. It is also proved from a rigorous mathematical analysis that the internal dynamics of the system remains stable when the proposed controller is applied. A robustness study is also carried out for testing the effectiveness of the drug administration scheme for parameter uncertainties. It is observed from simulation studies that the technique has adequate robustness for many �realistic model patients� having off-nominal parameter values as well.

Viscoelastic phenomenology based structure assignment for closed-loop vibration control of a beam with sensors and actuators

In this paper we incorporate a novel approach to synthesize a class of closed-loop feedback control, based on the variational structure assignment. Properties of a viscoelastic system are used to design an active feedback controller for an undamped structural system with distributed sensor, actuator and controller. Wave dispersion properties of onedimensional beam system have been studied. Efficiency of the chosen viscoelastic model in enhancing damping and stability properties of one-dimensional viscoelastic bar have been analyzed. The variational structure is projected on a solution space of a closed-loop system involving a weakly damped structure with distributed sensor and actuator with controller. These assign the phenomenology based internal strain rate damping parameter of a viscoelastic system to the usual elastic structure but with active control. In the formulation a model of cantilever beam with non-collocated actuator and sensor has been considered. The formulation leads to the matrix identification problem of two dynamic stiffness matrices. The method has been simplified to obtain control system gains for the free vibration control of a cantilever beam system with collocated actuator-sensor, using quadratic optimal control and pole-placement methods.

Swarm intelligence algorithms for integrated optimization of piezoelectric actuator and sensor placement and feedback gains

Swarm intelligence algorithms are applied for optimal control of flexible smart structures bonded with piezoelectric actuators and sensors. The optimal locations of actuators/sensors and feedback gain are obtained by maximizing the energy dissipated by the feedback control system. We provide a mathematical proof that this system is uncontrollable if the actuators and sensors are placed at the nodal points of the mode shapes. The optimal locations of actuators/sensors and feedback gain represent a constrained non-linear optimization problem. This problem is converted to an unconstrained optimization problem by using penalty functions. Two swarm intelligence algorithms, namely, Artificial bee colony (ABC) and glowworm swarm optimization (GSO) algorithms, are considered to obtain the optimal solution. In earlier published research, a cantilever beam with one and two collocated actuator(s)/sensor(s) was considered and the numerical results were obtained by using genetic algorithm and gradient based optimization methods. We consider the same problem and present the results obtained by using the swarm intelligence algorithms ABC and GSO. An extension of this cantilever beam problem with five collocated actuators/sensors is considered and the numerical results obtained by using the ABC and GSO algorithms are presented. The effect of increasing the number of design variables (locations of actuators and sensors and gain) on the optimization process is investigated. It is shown that the ABC and GSO algorithms are robust and are good choices for the optimization of smart structures.

Joint Performance Analysis of Channel Quality Indicator Feedback Schemes and Frequency-Domain Scheduling for LTE

Frequency-domain scheduling and rate adaptation enable next-generation orthogonal frequency-division multiple access (OFDMA) cellular systems such as Long-Term Evolution (LTE) to achieve significantly higher spectral efficiencies. LTE uses a pragmatic combination of several techniques to reduce the channel-state feedback that is required by a frequency-domain scheduler. In the subband-level feedback and user-selected subband feedback schemes specified in LTE, the user reduces feedback by reporting only the channel quality that is averaged over groups of resource blocks called subbands. This approach leads to an occasional incorrect determination of rate by the scheduler for some resource blocks. In this paper, we develop closed-form expressions for the throughput achieved by the feedback schemes of LTE. The analysis quantifies the joint effects of three critical components on the overall system throughput-scheduler, multiple-antenna mode, and the feedback scheme-and brings out its dependence on system parameters such as the number of resource blocks per subband and the rate adaptation thresholds. The effect of the coarse subband-level frequency granularity of feedback is captured. The analysis provides an independent theoretical reference and a quick system parameter optimization tool to an LTE system designer and theoretically helps in understanding the behavior of OFDMA feedback reduction techniques when operated under practical system constraints.

Decentralized linear quadratic power system stabilizers for multi-machine power systems

Linear quadratic stabilizers are well-known for their superior control capabilities when compared to the conventional lead-lag power system stabilizers. However, they have not seen much of practical importance as the state variables are generally not measurable; especially the generator rotor angle measurement is not available in most of the power plants. Full state feedback controllers require feedback of other machine states in a multi-machine power system and necessitate block diagonal structure constraints for decentralized implementation. This paper investigates the design of Linear Quadratic Power System Stabilizers using a recently proposed modified Heffron-Phillip's model. This model is derived by taking the secondary bus voltage of the step-up transformer as reference instead of the infinite bus. The state variables of this model can be obtained by local measurements. This model allows a coordinated linear quadratic control design in multi machine systems. The performance of the proposed controller has been evaluated on two widely used multi-machine power systems, 4 generator 10 bus and 10 generator 39 bus systems. It has been observed that the performance of the proposed controller is superior to that of the conventional Power System Stabilizers (PSS) over a wide range of operating and system conditions.

Material uncertainty effect on vibration control of smart composite plate using polynomial chaos expansion

Polynomial Chaos Expansion with Latin Hypercube sampling is used to study the effect of material uncertainty on vibration control of a smart composite plate with piezoelectric sensors/actuators. Composite material properties and piezoelectric coefficients are considered as independent and normally distributed random variables. Numerical results show substantial variation in structural dynamic response due to material uncertainty of active vibration control system. This change in response due to material uncertainty can be compensated by actively tuning the feedback control system. Numerical results also show variation in dispersion of dynamic characteristics and control parameters with respect to ply angle and stacking sequence.

Joint evaluation of channel feedback schemes, rate adaptation, and scheduling in OFDMA downlinks with feedback delays

Orthogonal frequency-division multiple access (OFDMA) systems divide the available bandwidth into orthogonal subchannels and exploit multiuser diversity and frequency selectivity to achieve high spectral efficiencies. However, they require a significant amount of channel state feedback for scheduling and rate adaptation and are sensitive to feedback delays. We develop a comprehensive analysis for OFDMA system throughput in the presence of feedback delays as a function of the feedback scheme, frequency-domain scheduler, and rate adaptation rule. Also derived are expressions for the outage probability, which captures the inability of a subchannel to successfully carry data due to the feedback scheme or feedback delays. Our model encompasses the popular best-n and threshold-based feedback schemes and the greedy, proportional fair, and round-robin schedulers that cover a wide range of throughput versus fairness tradeoff. It helps quantify the different robustness of the schedulers to feedback overhead and delays. Even at low vehicular speeds, it shows that small feedback delays markedly degrade the throughput and increase the outage probability. Further, given the feedback delay, the throughput degradation depends primarily on the feedback overhead and not on the feedback scheme itself. We also show how to optimize the rate adaptation thresholds as a function of feedback delay.

Common-Mode and Differential-Mode Active Damping for PWM Rectifiers

Modern pulse-width-modulated (PWM) rectifiers use LC L filters that can be applied in both the common mode and differential mode to obtain high-performance filtering. Interaction between the passive L and C components in the filter leads to resonance oscillations. These oscillations need to be damped either by the passive damping or active damping. The passive damping increases power loss and can reduce the effectiveness of the filter. Methods of active damping, using control strategy, are lossless while maintaining the effectiveness of the filters. In this paper, an active damping strategy is proposed to damp the oscillations in both line-to-line and line-to-ground. An approach based on pole placement by the state feedback is used to actively damp both the differential-and common-mode filter oscillations. Analytical expressions for the state-feedback controller gains are derived for both continuous and discrete-time model of the filter. Tradeoff in selection of the active damping gain on the lower order power converter harmonics is analyzed using a weighted admittance function. Experimental results on a 10-kVA laboratory prototype PWM rectifier are presented. The results validate the effectiveness of the active damping method, and the tradeoff in the settings of the damping gain.

PMV model is insufficient to capture subjective thermal response from Indians

A controlled laboratory experiment was carried out on forty Indian male college students for evaluating the effect of indoor thermal environment on occupants' response and thermal comfort. During experiment, indoor temperature varied from 21 degrees C to 33 degrees C, and the variables like relative humidity, airflow, air temperature and radiant temperature were recorded along with subject's physiological parameters (skin (T-sk) and oral temperature (T-c)) and subjective thermal sensation responses (TSV). From T-sk and T-c, body temperature (T-b) was evaluated. Subjective Thermal Sensation Vote (TSV) was recorded using ASHRAE 7-point scale. In PMV model, Fanger's T-sk equation was used to accommodate adaptive response. Step-wise regression analysis result showed T-b was better predictor of TSV than T-sk and T-c. Regional skin temperature response, suppressed sweating without dipping, lower sweating threshold temperature and higher cutaneous threshold for sweating were observed as thermal adaptive responses. These adaptive responses cannot be considered in PMV model. To incorporate subjective adaptive response, mean skin temperature (T-sk) is considered in dry heat loss calculation. Along with these, PMV-model and other two methodologies are adopted to calculate PMV values and results are compared. However, recent literature is limited to measure the sweat rate in Indians and consideration of constant Ersw in PMV model needs to be corrected. Using measured T-sk in PMV model (Method(1)), thermal comfort zone corresponding to 0.5 <= PMV <= 0.5 was evaluated as (22.46-25.41) degrees C with neutral temperature of 23.91 degrees C, similarly while using TSV response, wider comfort zone was estimated as (23.25-26.32) degrees C with neutral temperature at 24.83 degrees C, which was further increased to with TSV-PPDnew, relation. It was observed that PMV-model overestimated the actual thermal response. Interestingly, these subjects were found to be less sensitive to hot but more sensitive to cold. A new TSV-PPD relation (PPDnew) was obtained from the population distribution of TSV response with an asymmetric distribution of hot-cold thermal sensation response from Indians. The calculations of human thermal stress according to steady state energy balance models used on PMV model seem to be inadequate to evaluate human thermal sensation of Indians. Relevance to industry: The purpose of this paper is to estimate thermal comfort zone and optimum temperature for Indians. It also highlights that PMV model seems to be inadequate to evaluate subjective thermal perception in Indians. These results can be used in feedback control of HVAC systems in residential and industrial buildings. (C) 2014 Elsevier B.V. All rights reserved.

Multimodal therapy for complete regression of malignant melanoma using constrained nonlinear optimal dynamic inversion

Using a realistic nonlinear mathematical model for melanoma dynamics and the technique of optimal dynamic inversion (exact feedback linearization with static optimization), a multimodal automatic drug dosage strategy is proposed in this paper for complete regression of melanoma cancer in humans. The proposed strategy computes different drug dosages and gives a nonlinear state feedback solution for driving the number of cancer cells to zero. However, it is observed that when tumor is regressed to certain value, then there is no need of external drug dosages as immune system and other therapeutic states are able to regress tumor at a sufficiently fast rate which is more than exponential rate. As model has three different drug dosages, after applying dynamic inversion philosophy, drug dosages can be selected in optimized manner without crossing their toxicity limits. The combination of drug dosages is decided by appropriately selecting the control design parameter values based on physical constraints. The process is automated for all possible combinations of the chemotherapy and immunotherapy drug dosages with preferential emphasis of having maximum possible variety of drug inputs at any given point of time. Simulation study with a standard patient model shows that tumor cells are regressed from 2 x 107 to order of 105 cells because of external drug dosages in 36.93 days. After this no external drug dosages are required as immune system and other therapeutic states are able to regress tumor at greater than exponential rate and hence, tumor goes to zero (less than 0.01) in 48.77 days and healthy immune system of the patient is restored. Study with different chemotherapy drug resistance value is also carried out. (C) 2014 Elsevier Ltd. All rights reserved.

Strategies for three dimensional deployment of tethered satellites

Tethered satellites deployed from the Space Shuttle have been proposed for diverse applications. A funda- mental issue in the utilization of tethers is quick deployment and retrieval of the attached payload. Inordinate librations of the tether during deployment and retrieval is undesirable. The structural damping present in the system is too low to contain the librations. Rupp [1] proposed to control the tether reel located in the parent spacecraft to alter the tension in the tether, which in turn changes the stiffness and the damping of the system. Baker[2] applied the tension control law to a model which included out of plane motion. Modi et al.[3] proposed a control law that included nonlinear feedback of the out-of plane tether angular rate. More recently, nonlinear feedback control laws based on Liapunov functions have been proposed. Two control laws are derived in [4]. The first is based on partial decomposition of the equations of motion and utilization of a two dimensional control law developed in [5]. The other is based on a Liapunov function that takes into consideration out-of-plane motion. It is shown[4] that the control laws are effective when used in conjunction with out-of-plane thrusting. Fujii et al.,[6] used the mission function control approach to study the control law including aerodynamic drag effect explicitly into the control algorithm.

The regulation of the biosynthesis of ubiquinone in the rat

The urinary excretion of p-hydroxybenzoate was not altered by ubiquinone feeding, but, although decreased considerably, was not eliminated in protein deficiency. The incorporation of p-hydroxy[U-14C]benzaldehyde into ubiquinone in vivo increased in cold-exposed and p-chlorophenoxyisobutyrate (clofibrate)-fed rats, and these changes were parallel with the changes in the incorporation of [2-14C]mevalonate under these conditions. Starvation, cholesterol feeding and cholic acid feeding resulted in the decreased incorporation of p-hydroxy[U-14C]benzaldehyde into ubiquinone, confirming the decreased ubiquinone synthesis. Feeding exogenous ubiquinone increased the hepatic ubiquinone concentration, but did not cause any decrease in the incorporation of p-hydroxy[U-14C]benzaldehyde into ubiquinone, indicating the absence of a feedback control.

Modified ILMI algorithm for practical PID/PD implementation on a Micro Air Vehicle

This paper extends the iterative linear matrix inequality algorithm (ILMI) for systems having non-ideal PI, PD and PID implementations. The new algorithm uses the practical implementation of the feedback blocksto form the equivalent static output feedback plant. The LMI based synthesis techniques are used in the algorithm to design a multi-loop, multi-objective fixed structure control. The benefits of such a control design technique are brought out by applying it to the lateral stabilizing and tracking feedback control problem of a 30cm wingspan micro air vehicle.

Studies of the enzymes involved in nicotinamide adenine dinucleotide metabolism in Aspergillus niger

The enzyme nicotinamide amidase (nicotinamide amidohydrolase) was purified 57-fold from Aspergillus niger. The purified preparation was specific towards its substrate nicotinamide and did not deamidate NADP, NAD, NMN, N′-methyl nicotinamide, asparagine, glutamine, benzamide, α-naphthaleneamide and indoleacetamide. The asparagine, glutamine, benzamide, α-naphthaleneamide and indoleacetamide.vThe optimum pH was found to be 7.5. Temperature optimum was 40°. It had a Km value of 6.504 · 10−4 M towards nicotinamide. The enzyme exhibited Mg2+ ion requirement for its optimum activity. NAD-glycohydrolase (EC 3.2.2.5) was purified 109-fold from the mold. A. niger. The enzyme preparation was active only towards NAD and NADP and did not attack NMN, N′-methylnicotinamide and NADH. The Km value for NAD was found to be 7.693 · 10−6 M. The enzyme did not require any metal ion for its activity. It is suggested that A. niger will serve a better source for a large scale preparation of NAD-glycohydrolase than the Neurospora mold. The biological role of both NAD-glycohydrolase and nicotinamide amidase in the regulation of cellular NAD level has been discussed. It is, further, observed that NAD did not exert its feedback control on nicotinamide amidase at least in A. niger.

Some new concepts in nonlinear systems

Some new concepts characterizing the response of nonlinear systems are developed. These new concepts are denoted by the terms, the transient system equivalent, the response vector, and the space-phase components. This third concept is analyzed in comparison with the well-known technique of symmetrical components. The performance of a multiplicative feedback control system is represented by a nonlinear integro-differential equation; its solution is obtained by the principle of variation of parameters. The system response is treated as a vector and is resolved into its space-phase components. The individual effects of these components on the performance of the system are discussed. The suitability of the technique for the transient analysis of higher order nonlinear control systems is discussed.