V.K. Jain

In vivo radioprotection studies of 3,3′-diselenodipropionic acid, a selenocystine derivative

3,3-Diselenodipropionic acid (DSePA), a diselenide and a derivative of selenocystine, was evaluated for in vivo radioprotective effects in Swiss albino mice, at an intraperitoneal dose of 2 mg/kg body wt, for 5 days before whole-body exposure to gamma-radiation. The radioprotective efficacy was evaluated by assessing protection of the hepatic tissue, the spleen, and the gastrointestinal (GI) tract and survival against sub- and supralethal doses of gamma-radiation. DSePA inhibited radiation-induced hepatic lipid peroxidation, protein carbonylation, loss of hepatic function, and damage to the hepatic architecture. DSePA also attenuated the depletion of endogenous antioxidants such as glutathione, glutathione peroxidase, superoxide dismutase, and catalase in the livers of irradiated mice. DSePA also restored the radiation-induced reduction in villus height, crypt cell numbers, and spleen cellularity, indicating protective effects on the GI tract and the hematopoietic system. The results from single-cell gel electrophoresis of the peripheral blood leukocytes showed that DSePA can attenuate radiation-induced DNA damage. The mRNA expression analysis of genes revealed that DSePA augmented GADD45alpha and inhibited p21 in both spleen and liver tissues. DSePA also inhibited radiation-induced apoptosis in the spleen and reversed radiation-induced alterations in the expression of the proapoptotic BAX and the antiapoptotic Bcl-2 genes. In line with these observations, DSePA improved the 30-day survival of irradiated mice by 35.3%. In conclusion, these findings clearly confirm that DSePA exhibits protective effects against whole-body gamma-radiation and the probable mechanisms of action involve the maintenance of antioxidant enzymes, prophylactic action through the attenuation of the DNA damage, and inhibition of apoptosis.

A selenocysteine derivative therapy affects radiation-induced pneumonitis in the mouse.

The mechanism leading to the radiation-induced lung response of pneumonitis is largely unknown. Here we investigated whether treatment with 3,3-diselenodipropionic acid (DSePA), which reduces radiation-induced oxidative stress in acute response models, decreases the lung response to irradiation. Mice of the C3H/HeJ (alveolitis/pneumonitis-responding) strain received 18 Gy whole-thorax irradiation, and a subset of these mice was treated with DSePA (2 mg/kg) three times per week, beginning at 2 hours after radiation treatment, and continuing in the postirradiation period until death because of respiratory distress symptoms. DSePA treatment increased the postirradiation survival time of mice by an average of 32 days (P = 0.0002). Radiation-treated and DSePA-treated mice presented lower levels of lipid peroxidation and augmented glutathione peroxidase in the lungs, compared with those levels measured in mice receiving radiation only, when mice receiving radiation only were killed because of distress symptoms, whereas catalase and superoxide dismutase levels did not show consistent differences among treatment groups. DSePA treatment decreased pneumonitis and the numbers of mast cells, neutrophils, and lymphocytes in the lungs and bronchoalveolar lavage, respectively, of irradiated mice relative to mice exposed to radiation alone. DSePA treatment also decreased the radiation-induced increase in granulocyte colony-stimulating factor levels in the bronchoalveolar lavage and lung-tissue expression of intercellular adhesion molecule-1 and E-selectin, while increasing the expression of glutathione peroxidase-4. We conclude that DSePA treatment reduces radiation-induced pneumonitis in mice by delaying oxidative damage and the inflammatory cell influx.

An algorithm for determining the most reliable path of a network

Abstract This paper present an algorithm for determining the most reliable path between two specified vertices of a communication network, taking into account both the reliabilities of nodes and links. The proposed algorithm is based on the basic idea of node removal technique, which is generally used for finding Boolean transmission functions between input-output terminals in the analysis of bilateral switching networks. The proposed algorithm can be applied to oriented or non-oriented, symmetric or non-symmetric networks and is capable of handling networks with hundreds of nodes and links. The proposed algorithm is a good time saver and efficient for large networks, as compared to other existing methods.

An algorithm for determining the best path in a computer communication network

Abstract This paper presents an algorithm for determining the best path between two specified vertices of a computer communication network, taking into account the reliabilities and delay at nodes and of links. The network is modelled by a linear graph. The basic idea of node removal technique, which is generally used for finding Boolean-transmission functions between input-output terminals in the analysis of switching network, is extended to develop the proposed algorithm. The proposed algorithm can be applied to oriented or non-oriented, symmetric or non-symmetric networks and is capable of handling networks with hundreds of nodes and links. The proposed algorithm is a good time-saver and is efficient especially for large networks. The algorithm is explained with the help of a numerical example, which considers the well-known ARPA network.

Toxicological safety evaluation of 3,3′-diselenodipropionic acid (DSePA), a pharmacologically important derivative of selenocystine

ABSTRACT Diselenodipropionic acid (DSePA), a pharmacologically important derivative of selenocystine was evaluated for acute toxicity, mutagenic safety and metabolic stability. The estimated median oral lethal dose (LD50) cut‐off of DSePA in mice and rat models was ˜200 mg/kg and ˜25 mg/kg respectively, which is considerably higher than the reported oral LD50 dose of its parent compound. Subsequently DSePA treatment in absence and presence of rat liver S9 fraction was found to be non‐mutagenic at the tested doses up to 1 mM in rifampicin resistance assay and up to 6 mM in Ames test. In vitro degradation studies indicated that DSePA was more stable in S9 fraction of human compared to rat. The kinetic parameters Km and Vmax of DSePA degradation estimated using rat S9 fraction was 9.81 &mgr;M and 1.06 nmol/ml/min respectively. Further, DSePA treatment (1–50 &mgr;M) with or without rat S9 fraction did not induce any toxicity in human intestinal epithelial cells (Int 407) while showing comparable bioactivity of glutathione peroxidase (GPx) level. In conclusion, superior metabolic stability of DSePA in human S9 fraction with a concomitant lack of mutagenic effects suggests that it may be a suitable derivative of selenocytine for future biological studies. HighlightsLD50 of DSePA (oral) is 200 and 25 mg/kg body‐weight for mice and rat respectively.DSePA is relatively more stable in human S9 fraction compared to rat S9 fraction.DSePA with and without metabolic transformation was found to be non‐mutagenic.S9‐derived degradation of DSePA did not affect its toxicity and bioactivity in cells.

Predictive modeling of an industrial UASB reactor using NARX neural network

A NARX(Nonlinear Autoregressive Exogenous Input) neural network model of an industrial UASB reactor was developed in this research work. A total of 111 days data were used for the modeling process, specifically, 100 for training and 11 for comparison of predictions. Several designs were generated for the neural network to check the behavior of the predictive model during the training phase. The final design was optimized by observing performance characteristics and regression analysis by using a customized MATLAB script. The model was capable of realizing the dynamics of the system. A 5-6-2 architecture was capable of suitably modeling the UASB reactor and predicting values of biogas production rate and outlet COD concentration. Almost all predictions lied within ±10% deviations. Such a model may be utilized to predict the output of UASB reactor satisfactorily for its supervision, monitoring and control.

Optimum delay reliability distributed systems architecture

Abstract This paper deals with the combined problem of designing fault tolerant network topology and maximizing reliability for distributed communication networks. The resulting topologies maximize network reliability while reducing communication cost and delay simultaneously. The system architecture presented enjoys the advantages of low complexity, short routing distance (low communication delay) and is fault tolerant. Retaining the topology of communication network, enhancement of system reliability is undertaken next by altering the link arrangements. A simple and efficient heuristic algorithm for getting best arrangement of links is proposed and illustrated through an example.

A new method for system reliability bounds

Abstract It has been established that symbolic reliability evaluation problem is an N.P. complete problem and as such is computationally infeasible for large networks. This has led to increased efforts in search for more fast exact techniques as well as better approximate methods. This paper proposes an algorithm for determining improved (tighter) upper and lower bounds on system reliability of general (i.e. non-series-parallel) systems. The proposed algorithm, like most existing methods, requires the knowledge of all simple paths and minimal cutsets of the system. The system success (failure) function is the union of all simple paths (minimal cutsets). The system success and failure functions are then modified to multinominal form and these expressions are interpreted as proper probability expressions using some approximations. The proposed algorithm gives better bounds as compared to the min-max method, the method of successive bounds, Esary-Proschan bounds and Shogan bounds and is illustrated by an example.