Search results for: Sagardeep Talukdar
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 18

Search results for: Sagardeep Talukdar

18 Fokas-Lenells Equation Conserved Quantities and Landau-Lifshitz System

Authors: Riki Dutta, Sagardeep Talukdar, Gautam Kumar Saharia, Sudipta Nandy

Abstract:

Fokas-Lenells equation (FLE) is one of the integrable nonlinear equations use to describe the propagation of ultrashort optical pulses in an optical medium. A 2x2 Lax pair has been introduced for the FLE and from that solving the Riccati equation yields infinitely many conserved quantities. Thereafter for a new field function (S) of the Landau-Lifshitz (LL) system, a gauge equivalence of the FLE with the generalised LL equation has been derived. We hope our findings are useful for the application purpose of FLE in optics and other branches of physics.

Keywords: conserved quantities, fokas-lenells equation, landau-lifshitz equation, lax pair

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17 On the Hirota Bilinearization of Fokas-Lenells Equation to Obtain Bright N-Soliton Solution

Authors: Sagardeep Talukdar, Gautam Kumar Saharia, Riki Dutta, Sudipta Nandy

Abstract:

In non-linear optics, the Fokas-Lenells equation (FLE) is a well-known integrable equation that describes how ultrashort pulses move across optical fiber. It admits localized wave solutions, just like any other integrable equation. We apply the Hirota bilinearization method to obtain the soliton solution of FLE. The proposed bilinearization makes use of an auxiliary function. We apply the method to FLE with a vanishing boundary condition, that is, to obtain bright soliton. We have obtained bright 1-soliton, 2-soliton solutions and propose the scheme for obtaining N-soliton solution. We have used an additional parameter which is responsible for the shift in the position of the soliton. Further analysis of the 2-soliton solution is done by asymptotic analysis. We discover that the suggested bilinearization approach, which makes use of the auxiliary function, greatly simplifies the process while still producing the desired outcome. We think that the current analysis will be helpful in understanding how FLE is used in nonlinear optics and other areas of physics.

Keywords: asymptotic analysis, fokas-lenells equation, hirota bilinearization method, soliton

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16 Bright, Dark N-Soliton Solution of Fokas-Lenells Equation Using Hirota Bilinearization Method

Authors: Sagardeep Talukdar, Riki Dutta, Gautam Kumar Saharia, Sudipta Nandy

Abstract:

In non-linear optics, the Fokas-Lenells equation (FLE) is a well-known integrable equation that describes how ultrashort pulses move across the optical fiber. It admits localized wave solutions, just like any other integrable equation. We apply the Hirota bilinearization method to obtain the soliton solution of FLE. The proposed bilinearization makes use of an auxiliary function. We apply the method to FLE with a vanishing boundary condition, that is, to obtain a bright soliton solution. We have obtained bright 1-soliton and 2-soliton solutions and propose a scheme for obtaining an N-soliton solution. We have used an additional parameter that is responsible for the shift in the position of the soliton. Further analysis of the 2-soliton solution is done by asymptotic analysis. In the non-vanishing boundary condition, we obtain the dark 1-soliton solution. We discover that the suggested bilinearization approach, which makes use of the auxiliary function, greatly simplifies the process while still producing the desired outcome. We think that the current analysis will be helpful in understanding how FLE is used in nonlinear optics and other areas of physics.

Keywords: asymptotic analysis, fokas-lenells equation, hirota bilinearization method, soliton

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15 The Data-Driven Localized Wave Solution of the Fokas-Lenells Equation using PINN

Authors: Gautam Kumar Saharia, Sagardeep Talukdar, Riki Dutta, Sudipta Nandy

Abstract:

The physics informed neural network (PINN) method opens up an approach for numerically solving nonlinear partial differential equations leveraging fast calculating speed and high precession of modern computing systems. We construct the PINN based on strong universal approximation theorem and apply the initial-boundary value data and residual collocation points to weekly impose initial and boundary condition to the neural network and choose the optimization algorithms adaptive moment estimation (ADAM) and Limited-memory Broyden-Fletcher-Golfard-Shanno (L-BFGS) algorithm to optimize learnable parameter of the neural network. Next, we improve the PINN with a weighted loss function to obtain both the bright and dark soliton solutions of Fokas-Lenells equation (FLE). We find the proposed scheme of adjustable weight coefficients into PINN has a better convergence rate and generalizability than the basic PINN algorithm. We believe that the PINN approach to solve the partial differential equation appearing in nonlinear optics would be useful to study various optical phenomena.

Keywords: deep learning, optical Soliton, neural network, partial differential equation

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14 The Data-Driven Localized Wave Solution of the Fokas-Lenells Equation Using Physics-Informed Neural Network

Authors: Gautam Kumar Saharia, Sagardeep Talukdar, Riki Dutta, Sudipta Nandy

Abstract:

The physics-informed neural network (PINN) method opens up an approach for numerically solving nonlinear partial differential equations leveraging fast calculating speed and high precession of modern computing systems. We construct the PINN based on a strong universal approximation theorem and apply the initial-boundary value data and residual collocation points to weekly impose initial and boundary conditions to the neural network and choose the optimization algorithms adaptive moment estimation (ADAM) and Limited-memory Broyden-Fletcher-Golfard-Shanno (L-BFGS) algorithm to optimize learnable parameter of the neural network. Next, we improve the PINN with a weighted loss function to obtain both the bright and dark soliton solutions of the Fokas-Lenells equation (FLE). We find the proposed scheme of adjustable weight coefficients into PINN has a better convergence rate and generalizability than the basic PINN algorithm. We believe that the PINN approach to solve the partial differential equation appearing in nonlinear optics would be useful in studying various optical phenomena.

Keywords: deep learning, optical soliton, physics informed neural network, partial differential equation

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13 The Phosphatidate Phosphatase Pah1 and Its Regulator Nem1/spo7 Protein Phosphatase Required for Nucleophagy

Authors: Muhammad Arifur Rahman, Talukdar M. Waliullah, Takashi Ushimaru

Abstract:

Nucleophagy selectively degrades nuclear materials, especially nucleolus after nutrient starvation or inactivation of TORC1 kinase in budding yeast. Budding yeast phosphatidate (PA) phosphatase Pah1 that converts PA to diacylglycerol is essential for partitioning of lipid precursors between membrane and storage that is crucial for many aspects of cell growth and development. Pah1 is required for nuclear/ER membrane biogenesis and vacuole function, but whether Pah1 and its activator Nem1/Spo7 protein phosphatase complex are involved in autophagy is largely unknown. Loss of Pah1 causes expansion of the nucleus and fragmentation of the vacuole. Here we show that Pah1 is required for bulk autophagy and nucleophagy after TORC1 inactivation. Loss of Pah1 impaired nucleophagy severely and bulk autophagy to a lesser extent. Loss of the Pah1 activator Nem1-Spo7 protein phosphatase exhibited similar features.

Keywords: autophagy, Nem1/Spo7 phosphatase, Pah1, nucleophagy, TORC1

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12 Variation of Base Width of a Typical Concrete Gravity Dam under Different Seismic Conditions Using Static Seismic Loading

Authors: Prasanna Kumar Khaund, Sukanya Talukdar

Abstract:

A concrete gravity dam is a major hydraulic structure and it is very essential to consider the earthquake forces, to get a proper design base width, so that the entire weight of the dam resists the overturning moment due to earthquake and other forces. The main objective of this study is to obtain the design base width of a dam for different seismic conditions by varying the earthquake coefficients in both vertical and horizontal directions. This shall be done by equating the factor of safety against overturning, factor of safety against sliding and factor of safety against shear friction factor for a dam with their limiting values, under both tail water and no tail water condition. The shape of the Mettur dam in India is considered for the study. The study has been done taking a constant head of water at the reservoir, which is the maximum reservoir water level and a constant height of tail water. Using linear approximation method of Newton Raphson, the obtained equations against different factors of safety under different earthquake conditions are solved using a programme in C++ to get different values of base width of dam for varying earthquake conditions.

Keywords: design base width, horizontal earthquake coefficient, tail water, vertical earthquake coefficient

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11 Influence of Superplasticizer and Alkali Activator Concentration on Slag-Fly Ash Based Geopolymer

Authors: Sulaem Musaddiq Laskar, Sudip Talukdar

Abstract:

Sustainable supplementary cementitious material is the prime need in the construction industry. Geopolymer has strong potential for replacing the conventional Portland cement used in mortar and concrete in the industry. This study deals with experimental investigations performed on geopolymer mixes prepared from both ultra-fine ground granulated blast furnace slag and fly ash in a certain proportion. Geopolymer mixes were prepared with alkali activator composed of sodium hydroxide solution and varying amount of superplasticizer. The mixes were tested to study fresh and hardened state properties such as setting time, workability and compressive strength. Influence of concentration of alkali activator on effectiveness of superplasticizer in modifying the properties of geopolymer mixes was also investigated. Results indicated that addition of superplasticizer to ultra-fine slag-fly ash based geopolymer is advantageous in terms of setting time, workability and strength performance but up to certain dosage level. Higher concentration of alkali activator renders ineffectiveness in superplasticizer in improving the fresh and hardened state properties of geopolymer mixes.

Keywords: ultra-fine slag, fly ash, superplasticizer, setting time, workability, compressive strength

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10 Analysis of Cardiovascular Diseases Using Artificial Neural Network

Authors: Jyotismita Talukdar

Abstract:

In this paper, a study has been made on the possibility and accuracy of early prediction of several Heart Disease using Artificial Neural Network. (ANN). The study has been made in both noise free environment and noisy environment. The data collected for this analysis are from five Hospitals. Around 1500 heart patient’s data has been collected and studied. The data is analysed and the results have been compared with the Doctor’s diagnosis. It is found that, in noise free environment, the accuracy varies from 74% to 92%and in noisy environment (2dB), the results of accuracy varies from 62% to 82%. In the present study, four basic attributes considered are Blood Pressure (BP), Fasting Blood Sugar (FBS), Thalach (THAL) and Cholesterol (CHOL.). It has been found that highest accuracy(93%), has been achieved in case of PPI( Post-Permanent-Pacemaker Implementation ), around 79% in case of CAD(Coronary Artery disease), 87% in DCM (Dilated Cardiomyopathy), 89% in case of RHD&MS(Rheumatic heart disease with Mitral Stenosis), 75 % in case of RBBB +LAFB (Right Bundle Branch Block + Left Anterior Fascicular Block), 72% for CHB(Complete Heart Block) etc. The lowest accuracy has been obtained in case of ICMP (Ischemic Cardiomyopathy), about 38% and AF( Atrial Fibrillation), about 60 to 62%.

Keywords: coronary heart disease, chronic stable angina, sick sinus syndrome, cardiovascular disease, cholesterol, Thalach

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9 Non-Destructive Evaluation for Physical State Monitoring of an Angle Section Thin-Walled Curved Beam

Authors: Palash Dey, Sudip Talukdar

Abstract:

In this work, a cross-breed approach is presented for obtaining both the amount of the damage intensity and location of damage existing in thin-walled members. This cross-breed approach is developed based on response surface methodology (RSM) and genetic algorithm (GA). Theoretical finite element (FE) model of cracked angle section thin walled curved beam has been linked to the developed approach to carry out trial experiments to generate response surface functions (RSFs) of free, forced and heterogeneous dynamic response data. Subsequently, the error between the computed response surface functions and measured dynamic response data has been minimized using GA to find out the optimum damage parameters (amount of the damage intensity and location). A single crack of varying location and depth has been considered in this study. The presented approach has been found to reveal good accuracy in prediction of crack parameters and possess great potential in crack detection as it requires only the current response of a cracked beam.

Keywords: damage parameters, finite element, genetic algorithm, response surface methodology, thin walled curved beam

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8 Impact of a Locally-Prepared Fermented Alcoholic Beverage from Jaggery on the Gut Bacterial Profile of the Tea-Tribal Populations of Assam, India

Authors: Rupamoni Thakur, Madhusmita Dehingia, Narayan C. Talukdar, Mojibur R. Khan

Abstract:

The human gut is an extremely active fermentation site and is inhabited by diverse bacterial species. Consumption of alcoholic beverages has been shown to substantially modulate the human gut bacterial profile (GBP) of an individual. Assam, a major north-eastern state of India, is home to a number of tribal populations of which the tea-tribes form a major community. These tea-tribal communities are known to prepare and consume a locally-prepared alcoholic beverage from fermented jaggery, whose chemical composition is unknown. In this study, we demonstrate the effect of daily intake of the locally-prepared alcoholic beverage on the GBP of the tea-tribal communities and correlate it with the changes in the biochemical biomarkers of the population. The fecal bacterial diversity of 40 drinkers and 35 non-drinking healthy individuals were analyzed by polymerase chain reaction (PCR)–denaturing gradient gel electrophoresis (DGGE). The results suggested that the GBP was significantly modulated in the fermented-beverage consuming subjects. Significant difference was also observed in the serum biochemical parameters such as triglyceride, total cholesterol and the liver marker enzymes (ASAT/ALAT and GGT). Further studies to identify the GBP of drinkers vs non-drinkers through Next-generation Sequencing (NGS) analysis and to correlate the changes with the biochemical biomarkers of the population is underway.

Keywords: alcoholic beverage, gut bacterial profile, PCR-DGGE analysis, tea-tribes of India

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7 Monitoring Vaginal Electrical Resistance, Follicular Wave and Hormonal Profile during Estrus Cycle in Indigenous Sheep

Authors: T. A. Rosy, M. R. I. Talukdar, N. S. Juyena, F. Y. Bari, M. N. Islam

Abstract:

The ovarian follicular dynamics, vaginal electrical resistance (VER) and progesterone (P4) and estrogen (E2) profiles were investigated during estrus cycle in four indigenous ewes. Daily VER values were recorded with heat detector. The follicles were observed and measured by trans-rectal ultrasonography. Blood was collected daily for hormonal profiles. Results showed a significant variation in VER values (P<0.05) at estrus in regards to ewes and cycles. The day difference between two successive lower values in VER waves ranged from 13-17 days which might indicate the estrus cycle in indigenous ewes. Trans-rectal ultrasonography of ovaries revealed the presence of two to four waves of follicular growth during the study period. Results also showed that follicular diameter was negatively correlated with VER values. Study of hormonal profiles by ELISA revealed a positive correlation between E2 concentration and development of follicle and negative correlation between P4 concentration and development of follicle. The concentrations of estradiol increased at the time of estrus and then fall down in a basal level. Development of follicular size was accompanied by an increase in the concentration of serum estradiol. Inversely, when follicles heed to ovulation concentration of progesterone starts to fall down and after ovulation it turns its way to the zenith and remains at this state until next ovulatory follicle comes to its maximum diameter. This study could help scientists to set up a manipulative reproductive technique for improving genetic values of sheep in Bangladesh.

Keywords: ovarian follicle, hormonal profile, sheep, ultrasonography, vaginal electrical resistance

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6 Forgeability Study of Medium Carbon Micro-Alloyed Forging Steel

Authors: M. I. Equbal, R. K. Ohdar, B. Singh, P. Talukdar

Abstract:

Micro-alloyed steel components are used in automotive industry for the necessity to make the manufacturing process cycles shorter when compared to conventional steel by eliminating heat treatment cycles, so an important saving of costs and energy can be reached by reducing the number of operations. Micro-alloying elements like vanadium, niobium or titanium have been added to medium carbon steels to achieve grain refinement with or without precipitation strengthening along with uniform microstructure throughout the matrix. Present study reports the applicability of medium carbon vanadium micro-alloyed steel in hot forging. Forgeability has been determined with respect to different cooling rates, after forging in a hydraulic press at 50% diameter reduction in temperature range of 900-11000C. Final microstructures, hardness, tensile strength, and impact strength have been evaluated. The friction coefficients of different lubricating conditions, viz., graphite in hydraulic oil, graphite in furnace oil, DF 150 (Graphite, Water-Based) die lubricant and dry or without any lubrication were obtained from the ring compression test for the above micro-alloyed steel. Results of ring compression tests indicate that graphite in hydraulic oil lubricant is preferred for free forging and dry lubricant is preferred for die forging operation. Exceptionally good forgeability and high resistance to fracture, especially for faster cooling rate has been observed for fine equiaxed ferrite-pearlite grains, some amount of bainite and fine precipitates of vanadium carbides and carbonitrides. The results indicated that the cooling rate has a remarkable effect on the microstructure and mechanical properties at room temperature.

Keywords: cooling rate, hot forging, micro-alloyed, ring compression

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5 Effect of Austenitizing Temperature, Soaking Time and Grain Size on Charpy Impact Toughness of Quenched and Tempered Steel

Authors: S. Gupta, R. Sarkar, S. Pathak, D. H. Kela, A. Pramanick, P. Talukdar

Abstract:

Low alloy quenched and tempered steels are typically used in cast railway components such as knuckles, yokes, and couplers. Since these components experience extensive impact loading during their service life, adequate impact toughness of these grades need to be ensured to avoid catastrophic failure of parts in service. Because of the general availability of Charpy V Test equipment, Charpy test is the most common and economical means to evaluate the impact toughness of materials and is generally used in quality control applications. With this backdrop, an experiment was designed to evaluate the effect of austenitizing temperature, soaking time and resultant grain size on the Charpy impact toughness and the related fracture mechanisms in a quenched and tempered low alloy steel, with the aim of optimizing the heat treatment parameters (i.e. austenitizing temperature and soaking time) with respect to impact toughness. In the first phase, samples were austenitized at different temperatures viz. 760, 800, 840, 880, 920 and 960°C, followed by quenching and tempering at 600°C for 4 hours. In the next phase, samples were subjected to different soaking times (0, 2, 4 and 6 hours) at a fixed austenitizing temperature (980°C), followed by quenching and tempering at 600°C for 4 hours. The samples corresponding to different test conditions were then subjected to instrumented Charpy tests at -40°C and energy absorbed were recorded. Subsequently, microstructure and fracture surface of samples corresponding to different test conditions were observed under scanning electron microscope, and the corresponding grain sizes were measured. In the final stage, austenitizing temperature, soaking time and measured grain sizes were correlated with impact toughness and the fracture morphology and mechanism.

Keywords: heat treatment, grain size, microstructure, retained austenite and impact toughness

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4 Illustrative Effects of Social Capital on Perceived Health Status and Quality of Life among Older Adult in India: Evidence from WHO-Study on Global AGEing and Adults Health India

Authors: Himansu, Bedanga Talukdar

Abstract:

The aim of present study is to investigate the prevalence of various health outcomes and quality of life and analyzes the moderating role of social capital on health outcomes (i.e., self-rated good health (SRH), depression, functional health and quality of life) among elderly in India. Using WHO Study on Global AGEing and adults health (SAGE) data, with sample of 6559 elderly between 50 and above (Mage=61.81, SD=9.00) age were selected for analysis. Multivariate analysis accessed the prevalence of SRH, depression, functional limitation and quality of life among older adults. Logistic regression evaluates the effect of social capital along with other co-founders on SRH, depression, and functional limitation, whereas linear regression evaluates the effect of social capital with other co-founders on quality of life (QoL) among elderly. Empirical results reveal that (74%) of respondents were married, (70%) having low social action, (46%) medium sociability, (45%) low trust-solidarity, (58%) high safety, (65%) medium civic engagement and 37% reported medium psychological resources. The multivariate analysis, explains (SRH) is associated with age, female, having education, higher social action great trust, safety and greater psychological resources. Depression among elderly is greatly related to age, sex, education and higher wealth, higher sociability, having psychological resources. QoL is negatively associated with age, sex, being Muslim, whereas positive associated with higher education, currently married, civic engagement, having wealth, social action, trust and solidarity, safeness, and strong psychological resources.

Keywords: depressive symptom, functional limitation, older adults, quality of life, self rated health, social capital

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3 Corrosion Analysis of a 3-1/2” Production Tubing of an Offshore Oil and Gas Well

Authors: Suraj Makkar, Asis Isor, Jeetendra Gupta, Simran Bareja, Maushumi K. Talukdar

Abstract:

During the exploratory testing phase of an offshore oil and gas well, when the tubing string was pulled out after production testing, it was observed that there was visible corrosion/pitting in a few of the 3-1/2” API 5 CT L-80 Grade tubing. The area of corrosion was at the same location in all the tubing, i.e., just above the pin end. Since the corrosion was observed in the tubing within two months of their installation, it was a matter of concern, as it could lead to premature failures resulting in leakages and production loss and thus affecting the integrity of the asset. Therefore, the tubing was analysed to ascertain the mechanism of the corrosion occurring on its surface. During the visual inspection, it was observed that the corrosion was totally external, which was near the pin end, and no significant internal corrosion was observed. The chemical compositional analysis and mechanical properties (tensile and impact) show that the pipeline material was conforming to API 5 CT L-80 specifications. The metallographic analysis of the tubing revealed tempered martensitic microstructure. The grain size was observed to be different at the pin end as compared to the microstructure at base metal. The microstructures of the corroded area near threads reveal an oriented microstructure. The clearly oriented microstructure of the cold-worked zone near threads and the difference in microstructure represents inappropriate heat treatment after cold work. This was substantiated by hardness test results as well, which show higher hardness at the pin end in comparison to hardness at base metal. Scanning Electron Microscope (SEM) analysis revealed the presence of round and deep pits and cracks on the corroded surface of the tubing. The cracks were stress corrosion cracks in a corrosive environment arising out of the residual stress, which was not relieved after cold working, as mentioned above. Energy Dispersive Spectroscopy (EDS) analysis indicates the presence of mainly Fe₂O₃, Chlorides, Sulphides, and Silica in the corroded part indicating the interaction of the tubing with the well completion fluid and well bore environment. Thus it was concluded that residual stress after the cold working of male pins during threading and the corrosive environment acted in synergy to cause this pitting corrosion attack on the highly stressed zone along the circumference of the tubing just below the threaded area. Accordingly, the following suitable recommendations were given to avoid the recurrence of such corrosion problems in the wells. (i) After any kind of hot work/cold work, tubing should be normalized at full length to achieve uniform microstructure throughout its length. (ii) Heat treatment requirements (as per API 5 CT) should be part of technical specifications while at the procurement stage.

Keywords: pin end, microstructure, grain size, stress corrosion cracks

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2 Understanding the Dynamics of Human-Snake Negative Interactions: A Study of Indigenous Perceptions in Tamil Nadu, Southern India

Authors: Ramesh Chinnasamy, Srishti Semalty, Vishnu S. Nair, Thirumurugan Vedagiri, Mahesh Ganeshan, Gautam Talukdar, Karthy Sivapushanam, Abhijit Das

Abstract:

Snakes form an integral component of ecological systems. Human population explosion and associated acceleration of habitat destruction and degradation, has led to a rapid increase in human-snake encounters. The study aims at understanding the level of awareness, knowledge, and attitude of the people towards human-snake negative interaction and role of awareness programmes in the Moyar river valley, Tamil Nadu. The study area is part of the Mudumalai and the Sathyamangalam Tiger Reserves, which are significant wildlife corridors between the Western Ghats and the Eastern Ghats in the Nilgiri Biosphere Reserve. The data was collected using questionnaire covering 644 respondents spread across 18 villages between 2018 and 2019. The study revealed that 86.5% of respondents had strong negative perceptions towards snakes which were propelled by fear, superstitions, and threat of snakebite which was common and did not vary among different villages (F=4.48; p = <0.05) and age groups (X2 = 1.946; p = 0.962). Cobra 27.8% (n = 294) and rat snake 21.3% (n = 225) were the most sighted species and most snake encounter occurred during the monsoon season i.e., July 35.6 (n = 218), June 19.1% (n = 117) and August 18.4% (n = 113). At least 1 out of 5 respondents was reportedly bitten by snakes during their lifetime. The most common species of snakes that were the cause of snakebite were Saw scaled viper (32.6%, n = 42) followed by Cobra 17.1% (n = 22). About 21.3% (n = 137) people reported livestock loss due to pythons and other snakes 21.3% (n = 137). Most people, preferred medical treatment for snakebite (87.3%), whereas 12.7%, still believed in traditional methods. The majority (82.3%) used precautionary measure by keeping traditional items such as garlic, kerosene, and snake plant to avoid snakes. About 30% of the respondents expressed need for technical and monetary support from the forest department that could aid in reducing the human-snake conflict. It is concluded that the general perception in the study area is driven by fear and negative attitude towards snakes. Though snakes such as Cobra were widely worshiped in the region, there are still widespread myths and misconceptions that have led to the irrational killing of snakes. Awareness and innovative education programs rooted in the local context and language should be integrated at the village level, to minimize risk and the associated threat of snakebite among the people. Results from this study shall help policy makers to devise appropriate conservation measures to reduce human-snake conflicts in India.

Keywords: Envenomation, Health-Education, Human-Wildlife Conflict, Neglected Tropical Disease, Snakebite Mitigation, Traditional Practitioners

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1 High Throughput Virtual Screening against ns3 Helicase of Japanese Encephalitis Virus (JEV)

Authors: Soma Banerjee, Aamen Talukdar, Argha Mandal, Dipankar Chaudhuri

Abstract:

Japanese Encephalitis is a major infectious disease with nearly half the world’s population living in areas where it is prevalent. Currently, treatment for it involves only supportive care and symptom management through vaccination. Due to the lack of antiviral drugs against Japanese Encephalitis Virus (JEV), the quest for such agents remains a priority. For these reasons, simulation studies of drug targets against JEV are important. Towards this purpose, docking experiments of the kinase inhibitors were done against the chosen target NS3 helicase as it is a nucleoside binding protein. Previous efforts regarding computational drug design against JEV revealed some lead molecules by virtual screening using public domain software. To be more specific and accurate regarding finding leads, in this study a proprietary software Schrödinger-GLIDE has been used. Druggability of the pockets in the NS3 helicase crystal structure was first calculated by SITEMAP. Then the sites were screened according to compatibility with ATP. The site which is most compatible with ATP was selected as target. Virtual screening was performed by acquiring ligands from databases: KinaseSARfari, KinaseKnowledgebase and Published inhibitor Set using GLIDE. The 25 ligands with best docking scores from each database were re-docked in XP mode. Protein structure alignment of NS3 was performed using VAST against MMDB, and similar human proteins were docked to all the best scoring ligands. The low scoring ligands were chosen for further studies and the high scoring ligands were screened. Seventy-three ligands were listed as the best scoring ones after performing HTVS. Protein structure alignment of NS3 revealed 3 human proteins with RMSD values lesser than 2Å. Docking results with these three proteins revealed the inhibitors that can interfere and inhibit human proteins. Those inhibitors were screened. Among the ones left, those with docking scores worse than a threshold value were also removed to get the final hits. Analysis of the docked complexes through 2D interaction diagrams revealed the amino acid residues that are essential for ligand binding within the active site. Interaction analysis will help to find a strongly interacting scaffold among the hits. This experiment yielded 21 hits with the best docking scores which could be investigated further for their drug like properties. Aside from getting suitable leads, specific NS3 helicase-inhibitor interactions were identified. Selection of Target modification strategies complementing docking methodologies which can result in choosing better lead compounds are in progress. Those enhanced leads can lead to better in vitro testing.

Keywords: antivirals, docking, glide, high-throughput virtual screening, Japanese encephalitis, ns3 helicase

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