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Rama Rao K.V.S.N.,Jawaharlal Nehru Institute of Advanced Studies JNIAS | Battula S.K.,MLR Institute of Technology
Advances in Intelligent Systems and Computing

IDS is a powerful tool in monitoring intruders. It detects the intruders based on pre defined patterns known as signatures. But in the context of an enterprise, a single IDS for the whole organization may not function effectively as there will be several business units (domains) such as HR, Finance, Marketing etc. Each business unit will have its own set of activities, business rules and security requirements. It should be possible for the personnel in these enterprise business units to enter their own security business rules. Since many of these personnel do not have expertise in writing signature to IDS, it would be convenient for them to specify the rules in Natural Language statements like English. These natural language statements should be converted to IDS signatures and are supposed to be added to signature database. In this paper, we have provided an interface to enter rules in natural language. Using Sentimental Analysis technique, we processed the natural language statements for conversion to IDS signatures. The converted signatures are added to corresponding business domain signature database. These domain specific customized signatures will certainly enhance the security of an enterprise. © Springer India 2015. Source

Kavita Kumari K.,Jawaharlal Nehru Institute of Advanced Studies JNIAS | Setty O.H.,University of Hyderabad
Journal of Cancer Science and Therapy

Background: The combination of mitomycin C and cisplatin was proved to be beneficial in the treatment of lung cancer, breast cancer, anal carcinoma and human cervical cancer treatment. However, dose related toxicity happens to be one of the major concerns the treatment, leading to its discontinuation, although the patient's response is encouraging. The aim of the present investigation was to study the protective effects of Berberis aristata (10 mg/kg body weight) on the mitochondrial dysfunction caused due to administration of mitomycin C (2 mg/kg body wt, i.p) and cisplatin (12 mg/kg body wt, i.p). Methods: We have investigated the effects and protective effects on oxidative phosphorylation enzymes, of the electron transport system, lipid peroxidation and phospholipid composition in liver and kidney mitochondria. Results: Co-administration of mitomycin C and cisplatin resulted in significant decrease in active respiration (State 3 Respiration), Respiratory Control Ratio (RCR) and P/O ratio's using either succinate or glutamate plus malate as substrate. Altered enzyme activities of NADH dehydrogenase, succinate dehydrogenase, succinate- cytochrome c reductase, NADH-cytochrome c reductase, cytochrome c oxidase was observed. The level of lipid peroxides was increased, and with a significant decrease in phospholipid content. Prior administration of Berberis aristata protected against observed mitochondrial dysfunction. Conclusions: We believe that prior administration of Berberis aristata could reduce the damage to mitochondrial function, by scavenging free radicals and thereby, preventing uncoupling of oxidative phosphorylation, deactivation of enzymes of electron transport chain, generation of lipid peroxides, oxidation of phospholipids ultimately inhibiting the signaling wave propagation to the mitochondria death receptor (membrane bound cytochrome c), which generally leads to apoptosis. © 2012 Kavita Kumari K, et al. Source

Kumari K.K.,Jawaharlal Nehru Institute of Advanced Studies JNIAS | Setty O.H.,University of Hyderabad
Journal of Bioenergetics and Biomembranes

The evolving role of mitochondria, in mediating chemotherapy-induced apoptosis motivated us for the studies described here. The combination of cisplatin and cyclophosphamide is widely used in treating various types of cancers. The purpose of our study was to understand the mechanism of the toxicity induced by the co-administration of cisplatin and cyclophosphamide, on mitochondrial bioenergetics, and to study the protective effect of prior administration of the medicinal plant extract Phyllanthus fraternus. Our results reveal that co-administration of cisplatin (12 mg/kg, i.p) and cyclophosphamide (150 mg/kg, oral) to wistar rats (100 g) significantly alters mitochondrial structure and hence function. The rate of mitochondrial respiration was decreased significantly with both NAD + and FAD-linked substrates. The respiratory control ratio, an index of membrane integrity and the P/O ratio, a measure of phosphorylating efficiency also were decreased significantly accompanied by elevation in the lipid peroxide levels in liver, kidney homogenate and liver mitochondria respectively. Also, the phospholipid content of the mitochondrial membrane, showed a significant decrease, indicating mitochondrial membrane changes. Prior administration of an aqueous extract of P. fraternus (100 mg/kg) to rats, showed protection on all parameters investigated. Administration of P. fraternus alone did not show any significant changes on mitochondrial membrane bioenergetics. Thus, we propose, that the toxic side effects of cisplatin + cyclophosphamide, are due to a chain of interconnected events, within the mitochondrial inner membrane, ultimately leading to hepatotoxicity and nephrotoxicity. Further, our work also suggests that administration of aqueous extract of P. fraternus can enhance the therapeutic potential of anticancer drugs by reducing drug related toxicity. © 2012 Springer Science+Business Media, LLC. Source

Kakarala K.K.,Jawaharlal Nehru Institute of Advanced Studies JNIAS | Jamil K.,Jawaharlal Nehru Institute of Advanced Studies JNIAS
Molecular Phylogenetics and Evolution

Current methods of G protein coupled receptors (GPCRs) phylogenetic classification are sequence based and therefore inappropriate for highly divergent sequences, sharing low sequence identity. In this study, sequence structure profile based alignment generated by PROMALS3D was used to understand the GPCR Class A Rhodopsin superfamily evolution using the MEGA 5 software. Phylogenetic analysis included a combination of Neighbor-Joining method and Maximum Likelihood method, with 1000 bootstrap replicates. Our study was able to identify potential ligand association for Class A Orphans and putative/unclassified Class A receptors with no cognate ligand information: GPR21 and GPR52 with fatty acids; GPR75 with Neuropeptide Y; GPR82, GPR18, GPR141 with N-arachidonylglycine GPR176 with Free fatty acids, GPR10 with Tachykinin & Neuropeptide Y; GPR85 with ATP, ADP & UDP glucose; GPR151 with Galanin; GPR153 and GPR162 with Adrenalin, Noradrenalin; GPR146, GPR139, GPR142 with Neuromedin, Ghrelin, Neuromedin U-25 & Thyrotropin-releasing hormone GPR171 with ATP, ADP & UDP Glucose; GPR88, GPR135, GPR161, GPR101with 11-cis-retinal; GPR83 with Tackykinin; GPR148 with Prostanoids, GPR109b, GPR81, GPR31with ATP & UTP and GPR150 with GnRH I & GnRHII. Furthermore, we suggest that this study would prove useful in re-classification of receptors, selecting templates for homology modeling and identifying ligands which may show cross reactivity with other GPCRs as signaling via multiple ligands play a significant role in disease modulation. © 2014 Elsevier Inc. Source

Kakarala K.K.,Jawaharlal Nehru Institute of Advanced Studies JNIAS | Jamil K.,Jawaharlal Nehru Institute of Advanced Studies JNIAS
Journal of Receptors and Signal Transduction

Context: Drug resistance and drug-associated toxicity are the primary causes for withdrawal of many drugs, although patient recovery is satisfactory in many instances. Interestingly, the use of phytochemicals in the treatment of cancer as an alternative to synthetic drugs comes with a host of advantages; minimum side effects, good human absorption and low toxicity to normal cells. Protease activated receptor 1 (PAR1) has been established as a promising target in many diseases including various cancers. Strong evidences suggest its role in metastasis also. Objective: There are no natural compounds known to inhibit its activity, so we aimed to identify phytochemicals with antagonist activity against PAR1. Methods: We screened phytochemicals from Naturally Occurring Plant-based Anticancer Compound-Activity-Target database (NPACT, http://crdd.osdd.net/raghava/npact/) against PAR1 using virtual screening workflow of Schrödinger software. It analyzes pharmaceutically relevant properties using Qikprop and calculates binding energy using Glide at three accuracy levels (high-throughput virtual screening, standard precision and extra precision). Results and conclusion: Our study led to the identification of phytochemicals, which showed interaction with at least one experimentally determined active site residue of PAR1, showed no violations to Lipinski's rule of five along with predicted high human absorption. Furthermore, structural interaction fingerprint analysis indicated that the residues H255, D256, E260, S344, V257, L258, L262, Y337 and S344 may play an important role in the hydrogen bond interactions of the phytochemicals screened. Of these residues, H255 and L258 residues were experimentally proved to be important for antagonist binding. The residues Y183, L237, L258, L262, F271, L332, L333, Y337, L340, A349, Y350, A352, and Y353 showed maximum hydrophobic interactions with the phytochemicals screened. The results of this work suggest that phytochemicals Reissantins D, 24,25-dihydro-27-desoxywithaferin A, Isoguaiacin, 20-hydroxy-12-deoxyphorbol angelate, etc. could be potential antagonist of PAR1. However, further experimental studies are necessary to validate their antagonistic activity against PAR1. © 2014 Informa Healthcare USA, Inc. All rights reserved. Source

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