Search results for: Mowkshi Khullar

Authors: Gurleen Kour, Mowkshi Khullar, B. K. Chandan, Parvinder Pal Singh, Kushalava Reddy Yumpalla, Gurunadham Munagala, Ram A. Vishwakarma, Zabeer Ahmed

Abstract:

New chemotherapeutic compounds against multidrug-resistant Mycobacterium tuberculosis (Mtb) are urgently needed to combat drug resistance in tuberculosis (TB). Apart from in-vitro potency against the target, physiochemical properties and pharmacokinetic properties play an imperative role in the process of drug discovery. We have identified novel nitroimidazole derivatives with potential activity against mycobacterium tuberculosis. One lead candidates, MCD-017, which showed potent activity against H37Rv strain (MIC=0.5µg/ml) and was further evaluated in the process of drug development. Methods: Basic physicochemical parameters like solubility and lipophilicity (LogP) were evaluated. Thermodynamic solubility was determined in PBS buffer (pH 7.4) using LC/MS-MS. The partition coefficient (Log P) of the compound was determined between octanol and phosphate buffered saline (PBS at pH 7.4) at 25°C by the microscale shake flask method. The compound followed Lipinski’s rule of five, which is predictive of good oral bioavailability and was further evaluated for metabolic stability. In-vitro metabolic stability was determined in rat liver microsomes. The hepatotoxicity of the compound was also determined in HepG2 cell line. In vivo pharmacokinetic profile of the compound after oral dosing was also obtained using balb/c mice. Results: The compound exhibited favorable solubility and lipophilicity. The physical and chemical properties of the compound were made use of as the first determination of drug-like properties. The compound obeyed Lipinski’s rule of five, with molecular weight < 500, number of hydrogen bond donors (HBD) < 5 and number of hydrogen bond acceptors(HBA) not more then 10. The log P of the compound was less than 5 and therefore the compound is predictive of exhibiting good absorption and permeation. Pooled rat liver microsomes were prepared from rat liver homogenate for measuring the metabolic stability. 99% of the compound was not metabolized and remained intact. The compound did not exhibit cytoxicity in hepG2 cells upto 40 µg/ml. The compound revealed good pharmacokinetic profile at a dose of 5mg/kg administered orally with a half life (t1/2) of 1.15 hours, Cmax of 642ng/ml, clearance of 4.84 ml/min/kg and a volume of distribution of 8.05 l/kg. Conclusion : The emergence of multi drug resistance (MDR) and extensively drug resistant (XDR) Tuberculosis emphasize the requirement of novel drugs active against tuberculosis. Thus, the need to evaluate physicochemical and pharmacokinetic properties in the early stages of drug discovery is required to reduce the attrition associated with poor drug exposure. In summary, it can be concluded that MCD-017 may be considered a good candidate for further preclinical and clinical evaluations.

Keywords: mycobacterium tuberculosis, pharmacokinetics, physicochemical properties, hepatotoxicity

Procedia PDF Downloads 415

Authors: Kamalpreet Kaur, Harjit Pal Singh, Vikas Khullar

Abstract:

In Wireless Sensor Network (WSN), the main limitation is generally inimitable energy consumption during processing of the sensor nodes. Cluster head (CH) election is one of the main issues that can reduce the energy consumption. Therefore, discovering energy saving routing protocol is the focused area for research. In this paper, fuzzy-based energy aware routing protocol is presented, which enhances the stability and network lifetime of the network. Fuzzy logic ensures the well-organized selection of CH by taking four linguistic variables that are concentration, energy, centrality, and distance to base station (BS). The results show that the proposed protocol shows better results in requisites of stability and throughput of the network.

Keywords: ERA, fuzzy logic, network model, WSN

Procedia PDF Downloads 232

Authors: Sumanpreet Kaur, Harjit Pal Singh, Vikas Khullar

Abstract:

In Wireless Sensor Network (WSN), the sensor containing motes (nodes) incorporate batteries that can lament at some extent. To upgrade the energy utilization, clustering is one of the prototypical approaches for split sensor motes into a number of clusters where one mote (also called as node) proceeds as a Cluster Head (CH). CH selection is one of the optimization techniques for enlarging stability and network lifespan. Deterministic Stable Election Protocol (DSEP) is an effectual clustering protocol that makes use of three kinds of nodes with dissimilar residual energy for CH election. Fuzzy Logic technology is used to expand energy level of DSEP protocol by using fuzzy inference system. This paper presents protocol DSEP using Fuzzy Logic (DSEP-FL) CH by taking into account four linguistic variables such as energy, concentration, centrality and distance to base station. Simulation results show that our proposed method gives more effective results in term of a lifespan of network and stability as compared to the performance of other clustering protocols.

Keywords: DSEP, fuzzy logic, energy model, WSN

Procedia PDF Downloads 169

Authors: N. Singh, A. Khullar, R. Shrivastava, I. Singh, A. S. Kumar

Abstract:

Steel forms the basis of any modern society and is essential to economic growth. India’s annual crude steel production has seen a consistent increase over the past years and is poised to grow to 300 million tons per annum by 2030-31 from current level of 110-120 million tons per annum. Steel industry is highly capital-intensive industry and to remain competitive, it is imperative that it invests in operational excellence. Due to inherent nature of the industry, there is large amount of variability in its supply chain both internally and externally. Production and productivity of a steel plant is greatly affected by the bottlenecks present in material flow logistics. The internal logistics constituting of transport of liquid metal within a steel melting shop (SMS) presents an opportunity in increasing the throughput with marginal capital investment. The study was carried out at one of the SMS of an integrated steel plant located in the eastern part of India. The plant has three SMS’s and the study was carried out at one of them. The objective of this study was to identify means to optimize SMS hot metal logistics through application of industrial engineering techniques. The study also covered the identification of non-value-added activities and proposed methods to eliminate the delays and improve the throughput of the SMS.

Keywords: optimization, steel making, supply chain, throughput enhancement, workforce productivity

Procedia PDF Downloads 92