A Safe Vaccine (DV-STM-07) against Salmonella Infection Prevents Abortion and Confers Protective Immunity to the Pregnant and New Born Mice

Pregnancy is a transient immuno-compromised condition which has evolved to avoid the immune rejection of the fetus by the maternal immune system. The altered immune response of the pregnant female leads to increased susceptibility to invading pathogens, resulting in abortion and congenital defects of the fetus and a subnormal response to vaccination. Active vaccination during pregnancy may lead to abortion induced by heightened cell mediated immune response. In this study, we have administered the highly attenuated vaccine strain delta pmrG-HM-D (DV-STM-07) in female mice before the onset of pregnancy and followed the immune reaction against challenge with virulent S. Typhimurium in pregnant mice. Here we demonstrate that DV-STM-07 vaccine gives protection against Salmonella in pregnant mice and also prevents Salmonella induced abortion. This protection is conferred by directing the immune response towards Th2 activation and Th1 suppression. The low Th1 response prevents abortion. The use of live attenuated vaccine just before pregnancy carries the risk of transmission to the fetus. We have shown that this vaccine is safe as the vaccine strain is quickly eliminated from the mother and is not transmitted to the fetus. This vaccine also confers immunity to the new born mice of vaccinated mothers. Since there is no evidence of the vaccine candidate reaching the new born mice, we hypothesize that it may be due to trans-colostral transfer of protective anti-Salmonella antibodies. These results suggest that our vaccine DV-STM-07 can be very useful in preventing abortion in the pregnant individuals and confer immunity to the new born. Since there are no such vaccine candidates which can be given to the new born and to the pregnant women, this vaccine holds a very bright future to combat Salmonella induced pregnancy loss.

Effective treatment of infectious diseases: A nonlinear adaptive control theoretic approach

A nonlinear adaptive system theoretic approach is presented in this paper for effective treatment of infectious diseases that affect various organs of the human body. The generic model used does not represent any specific disease. However, it mimics the generic immunological dynamics of the human body under pathological attack, including the response to external drugs. From a system theoretic point of view, drugs can be interpreted as control inputs. Assuming a set of nominal parameters in the mathematical model, first a nonlinear controller is designed based on the principle of dynamic inversion. This treatment strategy was found to be effective in completely curing "nominal patients". However, in some cases it is ineffective in curing "realistic patients". This leads to serious (sometimes fatal) damage to the affected organ. To make the drug dosage design more effective, a model-following neuro-adaptive control design is carried out using neural networks, which are trained (adapted) online. From simulation studies, this adaptive controller is found to be effective in killing the invading microbes and healing the damaged organ even in the presence of parameter uncertainties and continuing pathogen attack.

A neuro-adaptive augmented optimal dynamic inversion approach for effective and efficient treatment of chronic myelogenous leukemia

Combining the advanced techniques of optimal dynamic inversion and model-following neuro-adaptive control design, an efficient technique is presented for effective treatment of chronic myelogenous leukemia (CML). A recently developed nonlinear mathematical model for cell dynamics is used for the control (medication) synthesis. First, taking a set of nominal parameters, a nominal controller is designed based on the principle of optimal dynamic inversion. This controller can treat nominal patients (patients having same nominal parameters as used for the control design) effectively. However, since the parameters of an actual patient can be different from that of the ideal patient, to make the treatment strategy more effective and efficient, a model-following neuro-adaptive controller is augmented to the nominal controller. In this approach, a neural network trained online (based on Lyapunov stability theory) facilitates a new adaptive controller, computed online. From the simulation studies, this adaptive control design approach (treatment strategy) is found to be very effective to treat the CML disease for actual patients. Sufficient generality is retained in the theoretical developments in this paper, so that the techniques presented can be applied to other similar problem as well. Note that the technique presented is computationally non-intensive and all computations can be carried out online.

Adaptive load control of the central processor in a distributed system with a star topology

The author presents adaptive control techniques for controlling the flow of real-time jobs from the peripheral processors (PPs) to the central processor (CP) of a distributed system with a star topology. He considers two classes of flow control mechanisms: (1) proportional control, where a certain proportion of the load offered to each PP is sent to the CP, and (2) threshold control, where there is a maximum rate at which each PP can send jobs to the CP. The problem is to obtain good algorithms for dynamically adjusting the control level at each PP in order to prevent overload of the CP, when the load offered by the PPs is unknown and varying. The author formulates the problem approximately as a standard system control problem in which the system has unknown parameters that are subject to change. Using well-known techniques (e.g., naive-feedback-controller and stochastic approximation techniques), he derives adaptive controls for the system control problem. He demonstrates the efficacy of these controls in the original problem by using the control algorithms in simulations of a queuing model of the CP and the load controls.

Optimal Blood Glucose Regulation using Single Network Adaptive Critics

Diabetes is a serious disease during which the body's production and use of insulin is impaired, causing glucose concentration level toincrease in the bloodstream. Regulating blood glucose levels as close to normal as possible, leads to a substantial decrease in long term complications of diabetes. In this paper, an intelligent neural network on-line optimal feedback treatment strategy based on nonlinear optimal control theory is presented for the disease using subcutaneous treatment strategy. A simple mathematical model of the nonlinear dynamics of glucose and insulin interaction in the blood system is considered based on the Bergman's minimal model. A glucose infusion term representing the effect of glucose intake resulting from a meal is introduced into the model equations. The efficiency of the proposed controllers is shown taking random parameters and random initial conditions in presence of physical disturbances like food intake. A comparison study with linear quadratic regulator theory brings Out the advantages of the nonlinear control synthesis approach. Simulation results show that unlike linear optimal control, the proposed on-line continuous infusion strategy never leads to severe hypoglycemia problems.

New a posteriori error estimator and adaptive mesh refinement strategy for 2-D crack problems

A posteriori error estimation and adaptive refinement technique for fracture analysis of 2-D/3-D crack problems is the state-of-the-art. The objective of the present paper is to propose a new a posteriori error estimator based on strain energy release rate (SERR) or stress intensity factor (SIF) at the crack tip region and to use this along with the stress based error estimator available in the literature for the region away from the crack tip. The proposed a posteriori error estimator is called the K-S error estimator. Further, an adaptive mesh refinement (h-) strategy which can be used with K-S error estimator has been proposed for fracture analysis of 2-D crack problems. The performance of the proposed a posteriori error estimator and the h-adaptive refinement strategy have been demonstrated by employing the 4-noded, 8-noded and 9-noded plane stress finite elements. The proposed error estimator together with the h-adaptive refinement strategy will facilitate automation of fracture analysis process to provide reliable solutions.

Adaptive dendron: A bile acid oligomer behaving as both normal and inverse micellar mimic

The normal and inverse micellar property of a bile-acid-based dendritic structure was established through dye solubilization studies in both polar and nonpolar media.

Power System Stability Enhancement by Single Network Adaptive Critic Stabilizers

This paper proposes a Single Network Adaptive Critic (SNAC) based Power System Stabilizer (PSS) for enhancing the small-signal stability of power systems over a wide range of operating conditions. SNAC uses only a single critic neural network instead of the action-critic dual network architecture of typical adaptive critic designs. SNAC eliminates the iterative training loops between the action and critic networks and greatly simplifies the training procedure. The performance of the proposed PSS has been tested on a Single Machine Infinite Bus test system for various system and loading conditions. The proposed stabilizer, which is relatively easier to synthesize, consistently outperformed stabilizers based on conventional lead-lag and linear quadratic regulator designs.

Confirmation of pauling's theory that vitamin C improves immunity to infection

It is pointed out that the complement Clq, associated with the immune response system, has a part containing about 80 residues with a collagen-like sequence, with Gly at every third location and having also a number of Hyp and Hyl residues in locations before Gly, and that it takes the triple-helical conformation characteristic of collagen. As with collagen biosynthesis, ascorbic acid is therefore expected to be required for its production. Also, collagen itself, in the extracellular matrix, is connected with the fibroblast surface protein (FSP), whose absence leads to cell proliferation, and whose addition leads to suppression of malignancy in tissue culture. All these show the great importance of vitamin C for resistance to diseases, and even to cancer, as has been widely advocated by Pauling.

Comparative study of adaptive frequency hopping with power control to avoid WLAN interference in WPAN systems like Bluetooth

Presently Bluetooth(BT) is one of the widely used device for personal communication. As BT devices are operating in the unlicensed ISM band, they are often subjected to the interference from WLAN. The band width of BT (1MHz) is narrower compare to the bandwidth of WLAN (22MHz). So for coexistence purpose it is important to observe the performance of narrow band signal BT in presence of wideband interference WLAN and vice versa. As there are many work on the performance of WLAN in presence BT interference 3]4]5]6], the main focus in this paper is on performance of BT in presence of WLAN interference in AWGN, Rayleigh fading channel. Then comparison of the performance using interference avoidance technique like adaptive frequency hopping, power control for BT system is given. Finally a conclusion is drawn observing the simulation results on the technique which is more suitable for WLAN interference mitigation in BT system.

A structural principle for a class of adaptive systems

A feature common to many adaptive systems for identification and control is the adjustment.of gain parameters in a manner ensuring the stability of the overall system. This paper puts forward a principle which assures such a result for arbitrary systems which are linear and time invariant except for the adjustable parameters. The principle only demands that a transfer function be positive real. This transfer function dependent on the structure of the system with respect to the parameters. Several examples from adaptive identification, control and observer schemes are given as illustrations of the conceptual simplification provided by the structural principle.

Adaptive optimal load balancing in a nonhomogeneous multiserver system with a central job scheduler

A model comprising several servers, each equipped with its own queue and with possibly different service speeds, is considered. Each server receives a dedicated arrival stream of jobs; there is also a stream of generic jobs that arrive to a job scheduler and can be individually allocated to any of the servers. It is shown that if the arrival streams are all Poisson and all jobs have the same exponentially distributed service requirements, the probabilistic splitting of the generic stream that minimizes the average job response time is such that it balances the server idle times in a weighted least-squares sense, where the weighting coefficients are related to the service speeds of the servers. The corresponding result holds for nonexponentially distributed service times if the service speeds are all equal. This result is used to develop adaptive quasi-static algorithms for allocating jobs in the generic arrival stream when the load parameters are unknown. The algorithms utilize server idle-time measurements which are sent periodically to the central job scheduler. A model is developed for these measurements, and the result mentioned is used to cast the problem into one of finding a projection of the root of an affine function, when only noisy values of the function can be observed

Low frequency oscillations in power systems: A physical account and adaptive stabilizers

This paper presents a physical explanation of the phenomenon of low frequency oscillations experienced in power systems. A brief account of the present practice of providing fixed gain power system stabilizers (PSS) is followed by a summary of some of the recent design proposals for adaptive PSS. A novel PSS based on the effort of cancelling the negative damping torque produced by the automatic voltage regulator (AVR) is presented along with some recent studies on a multimachine system using a frequency identification technique.