International journal of scientific and innovative research 2018; 5(2)p issn 2347 2189, e issn 2347

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VOLUME – 5, ISSUE – 2 (JULY-DECEMBER) 2017


Editorial

I am happy to convey that second issue of third volume of "International Journal of Scientific and Innovative Research (IJSIR)", a bi-annual journal has been published by Sky Institute, Lucknow in an effort to promote multidisciplinary scientific and innovative research of societal benefit. This journal covers all branches of science, technology, engineering, health, agriculture and management. Research articles in the field of education are also encouraged in order to promote educational technology aiming at improvement in present educational system. As research and development (R & D) has been playing a significant role in overall development of society, continuous multidisciplinary innovative research in science and technology is needed to address the challenges in context to changing environmental conditions in the present era of gradual increase in industrial and technological advancement at global level. Efforts should be made to develop eco-friendly technologies in order to provide solutions for developing socially, economically and culturally sustainable society. The present issue of International Journal of Scientific and Innovative Research (IJSIR) contains 18 research papers I articles covering different areas of science and technology. All these papers are well written and informative in content. I express my thanks to members of Committee for Editorial Assistance Dr. B.C.Tripathi, Dr. Pankaj Verma, Shri Sanjay Pandey, Shri Sanjay Dixit and Mr. Shamshul Hasan Khan for their hard work and devotion in giving the final shape to the journal. I am thankful to all faculty members, scientists and research scholars of different universities, research organizations and technical institutions for contributing their research articles for publication in the present issue of the journal. The help provided by faculty members and supporting staff of Sky Institute in publishing the present volume of the journal is also acknowledged. I hope scientists, academicians and young researchers will be greatly benefited by this publication for their research work. I request humbly to the readers and contributors of our journal to continue encouraging us for regular publication of the journal. Any suggestion and comment for the improvement in the quality of the journal are always welcome.

Dr. B. R. Pandey Editor-in-Chief


International Journal of Scientific and Innovative Research 2017; 5(2) P‐ISSN 2347‐2189, E‐ ISSN 2347‐4971

EDITOR-IN-CHIEF Dr. B.R. Pandey Director (Research) Sky Institute, Kursi Road, Lucknow, U.P, India

Dean, Faculty of Science & Technology, Sai Nath University, Jharkhand, India Former Joint Director, Council of Science & Technology, UP, Lucknow (Department of Science and Technology, UP Government), India Former Professor, International Institute of Herbal Medicine (IIHM), Lucknow, U.P., India E-mail Id: editorijsir02@gmail.com, Mobile-: 9794849800

COMMITTEE FOR EDITORIAL ASSISTANCE Dr. B.C.Tripathi Assistant Prof., Deptt. of Education, Rama P.G. College, Chinhat, Lucknow, Uttar Pradesh

Dr. Pankaj Verma Senior Research Fellow, Deptt. of Oral & Maxillofacial Surgery, Faculty of Dental Sciences, K.G. Medical University, Lucknow, Uttar Pradesh

Shri Sanjay Pandey Assistant Prof., National Institute of Fashion Technology, Raebareli, Uttar Pradesh

Shri Ashish Tiwari Research Scholar, Sai Nath University, Ranchi, Jharkhand

Shri Sanjay Dixit Scientist, Sky Institute, Lucknow, Uttar Pradesh

Shamshul Hasan Khan Scientist, Sky Institute, Lucknow, Uttar Pradesh

ADVISORY BOARD Prof.(Dr.)S. P. Ojha

Prof. (Dr.) R. L. Singh

Former Vice Chancellor, CCS Meerut University, Meerut, Uttar Pradesh

Prof & Head, Department of Biochemistry & Coordinator Biotechnology Program , Dr. R. M. L. University Faizabad, Uttar Pradesh

Prof.(Dr.)V.K. Srivastava Former Prof & Head, Deptt. of Community Medicine King George Medical

Dr. Sarita Verma

University, Lucknow. Former Director, Integral Institute of Medical Sciences & Research, Integral University, Lucknow Former Vice -Chancellor, Texila American University, Georgetown, Guyana, South America

Head, Deptt. of Home Sci., Mahila P.G. College, Kanpur, Uttar Pradesh

Prof.(Dr.) M.I. Khan Prof & Head, Deptt. of Mechanical Engg., Integral University, Lucknow, Uttar Pradesh

Prof. (Dr.) S.K. Avasthi Former Director, H.B.T.I., Kanpur, Uttar Pradesh

Prof.(Dr.) Amrika Singh Prof & Head (Chemistry), Deptt. of Applied Sciences, Institute of Engg. & Technology, Sitapur Road, Lucknow, Uttar Pradesh

Prof. (Dr.) U.N. Dwivedi Prof & Ex- Head, Deptt of Biochemistry, Former Pro- Vice Chancellor, Former Dean, Faculty of Science, University of Lucknow, Lucknow, U.P.

Prof. (Dr.) U.K. Misra Head, Deptt. of Neurology, Ex Dean, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, U.P.

Dr. A.K. Gupta Former Deputy Director General, Indian Council of Medical Research (ICMR), Ansari Nagar, New Delhi

Prof.(Dr.) V.K.Tondon Former Prof & Head, Deptt. of Chemistry, Ex- Dean Faculty of Science, University of Lucknow, Lucknow, Uttar Pradesh

Prof. (Dr.) Amod Kumar Tiwari, Prof.- Director, Bhabha Institute of Engg.& Technology, Kanpur, U.P.

Prof.(Dr.) Chandra Dhar Dwivedi Former Prof. & Chairman, Deptt. of Pharmaceutical Sciences, College of Pharmacy, South Dakota State University, Borokings, South Dakota, USA

Prof. (Dr.) Vimal Kishore Prof. & Chairman, Deptt. of Basic Pharmaceutical Sciences, Xevier College of Pharmacy, University of Louisiana, 7325, Palmetto Street New Orlens, Louisiana USA

Prof. (Dr.) S.P. Singh Former Prof & Head, Deptt. of Pharmacology, G. S. V. M. Medical College, Kanpur, Uttar Pradesh

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Prof. (Dr.) S.K.Agarwal Pro. & Ex-Head, Deptt. of Biochemistry, Lucknow University, Lucknow, U.P.

Dr. Bharat Sah Director, National Institute of Fashion Technology, Raebareli, Uttar Pradesh

Prof. (Dr.)N.S. Verma Prof., Deptt. of Physiology, K. G. Medical University, Lucknow, Uttar Pradesh

Prof. (Dr.)A.K. Tripathi Prof. & Head, Deptt. of Clinical Hematology & Medical Oncology, K. G. Medical University, Lucknow, Uttar Pradesh

Prof.(Dr.)C.M. Pandey Prof. & Head, Deptt. of Biostatistics & Health Informatics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh

Dr. Rupesh Chaturvedi Associate Prof., School of Biotechnology, Jawaharlal Nehru University, New Delhi, Former Asstt. Prof., Deptt. of Pharmaceutical Sciences , College of Pharmacy, Vanderbilt University, Tennessee, USA

Dr. S.Sinha Asstt. Prof. Deptt. of Internal Medicine, CD University, C. David Giffen School of Medi., University of California, Los Angeles, USA

Dr. K.Raman Principal Scientist, Martek Biosciences Corporation, 6480 Dobbin Road, Columbia, MD 21045, USA Dr. P.K.Agarwal Editor –in – Chief, Natural Product Communication, Natural Product Inc 7963, Anderson Park Lane West Terville, OH, USA

Dr. R.K.Singh, Chief Scientist, Division of Toxicology, CSIR-Central Drug Research Institute, Jankipuram Extension, Lucknow, Uttar Pradesh

Dr. Mohd. Tarique Prof., Deptt of Physical Edu., Lucknow University, Lucknow, Uttar Pradesh


International Journal of Scientific and Innovative Research 2017; 5(2) P‐ISSN 2347‐2189, E‐ ISSN 2347‐4971

EDITORIAL BOARD Prof.(Dr.) Y.B. Tripathi

Dr. K.K.Verma

Prof. & Head, Deptt. of Medicinal Chemistry,Institute of Medical Sciences, Banaras Hindu University Varanasi, Uttar Pradesh

Assoc. Prof., Deptt. of Physics & Electronics.Dr. R. M. L. Awadh University , Faizabad,Uttar Pradesh

Prof.(Dr.) R.K. Singh

Dr. Atul Gupta

Prof. & Head , Deptt. of Biochemistry, Shri Guru Ram RaiInstitute of Medical & Health Senior Scientist, CSIR- Central Institute of Medicinal & Aromatic Plants, Sciences, Dehradun, Uttarakhand & Former Prof. & Head, Department of Biochemistry, Lucknow, Uttar Pradesh K. G. Medical University, Lucknow, U.P. Dr. Saudan Singh,

Prof. (Dr.) R.S.Diwedi Senior Principal Scientist, CSIR- Central Institute of Medicinal & Aromatic Former Director, National Research Centre for Groundnut (NRCG) , ICAR, Junagarh, Plants , Lucknow, Uttar Pradesh Gujarat & Former Principal Scientist – Head, Deptt. of Plant Physiology, Indian Institute Dr. S.K.Tiwari of Sugarcane Research, Lucknow, Uttar Pradesh Senior Principal Scientist ,CSIR- National Botanical Research Institute, Prof. (Dr.) Nuzhat Husain Lucknow, Uttar Pradesh Prof. & Head , Deptt of Pathology & Acting Director, R. M. L. Institute of Medical Dr. Shivani Pandey, Sciences, Lucknow,Uttar Pradesh Asstt. Prof., Deptt. of Biochemistry,K.G.Medical University, Lucknow, U.P.

Prof. (Dr.) Amita Jain

Prof. Deptt. of Microbiology, K.G. Medical University, Lucknow, U.P.

Dr. Sudhir Mahrotra Associate Prof., Deptt. of Biochemistry, Lucknow University, Lucknow, U.P.

Prof. (Dr.) Vibha Singh Prof., Deptt. of Oral & Maxillofacial Surgery, Faculty of Dental Sciences, K. G. Medical University, Lucknow, Uttar Pradesh

Prof. (Dr.) U.S. Pal Prof. & Head, Deptt. of Oral & Maxillofacial Surgery, Faculty of Dental Sciences, K. G. Medical University, Lucknow, Uttar Pradesh

Prof. (Dr. ) K.K. Pant Prof. & Head, Deptt. of Pharmacology & Therapeutics, K. G. Medical University, Lucknow, Uttar Pradesh

Dr. B.C. Yadav, Lucknow Associate Prof. & Coordinator, Deptt. of Applied Physics, School for Physical Sciences, Babasaheb Bhimrao Ambedkar University, Lucknow, U.P.

Dr. Shalini Bariar Associate Professor, Thakur Institute of Management Studies and Research,, Mumbai, India Dr.A.K.Pandey Principal Scientist, National Bureau of Fish Genetic Resources,Lucknow, U.P.

Dr.S.K.Pandey G.M. LML Factory, Kanpur Uttar Pradesh

Dr. Suneet Kumar Awasthi, Asst. Prof, Deptt.of Physics J.P. University, Noida, Uttar Pradesh

Dr. C.M.K.Tripathi

Dr.G. N. Pandey

Former Deputy Director & Head, Division of Fermentation Technology, CSIR- Central Drug Research Institute , Lucknow, Uttar Pradesh

Dr. Mukesh Verma

Dr. R.D. Tripathi Chief Scientist & ProfessorPlant Ecology & Environmental Science Division, Uttar Pradesh CSIR-National Botanical Research Institute, Lucknow, U.P.

Asst. Prof, Deptt. of Physics Amity University, Noida ,Uttar Pradesh Asst. Prof., Deptt. of Physical Education, Dr. R.M.L. Avadh University, Faizabad, Uttar Pradesh

Dr. Abhay Singh,

Prof.(Dr.) Ashwani K. Srivastav

Head, Physical Education, Delhi Public School, Lucknow Uttar Pradesh

Prof. & Head, Deptt. of Biosciences, Integral University,Lucknow, Former Senior Scientist, Birbal Sbahani Institute Paleobotany, Lucknow, U.P.

Dr. Santosh Gaur

Prof.(Dr.) L. Pandey

Asst. Prof. Deptt. of Physical Education, Jawahar Lal Nehru P.G. College, Barabanki, Uttar Pradesh

Dr.Sanjeev Kumar Jha

Prof. & Head , Postgraduate Deptt . of Physics,Former Dean, Faculty of Science, Rani Durgawati University, Jabalpur, Madhya Pradesh, India

Senior Scientist, DEOACC Patna

Prof .(Dr.) Bali Ram

Dr. Shivlok Singh

Prof., Deptt. of Chemistry, Banaras Hindu University, Varanasi, Uttar Pradesh

Scientist, DEOACC, Lucknow, Uttar Pradesh

Prof.(Dr.) J.P.N.Rai

Dr. Anurag Tripathi,

Prof.& Head, Deptt. of Environmental Sciences, G.B. Pant University of Agr. & Technology, Pant Nagar, Uttarakhand

Asstt . Prof. , Deptt. of Electrical Engg., Institute of Engg. & Technology, Sitapur Road, Lucknow, Uttar Pradesh

Prof.(Dr. )R. S. Dubey

Prof. V.P.Sharma

Prof. & Head, Deptt. of Biochemistry, Banaras Hindu University, Varanasi, U.P.

Senior Principal Scientist, CSIR-Indian Institute of Toxicology Research, Lucknow, Uttar Pradesh

Prof. (Dr.) Omkar Deptt. of Zoology, Lucknow University, Lucknow, Uttar Pradesh

Dr. Krishna Gopal

Prof.(Dr.) Sudhir Kumar

Former Deputy Director & Head , Aquatic Toxicology Division, CSIR- Indian Institute of Toxicology Research, Lucknow, Uttar Pradesh

Prof., Deptt. of Zoology, Lucknow University, Lucknow, Uttar Pradesh

Prof.(Dr.) Naveen Khare Prof., Deptt. of Chemistry, Lucknow University, Lucknow, Uttar Pradesh

Prof.(Dr.) S. M. Natu Prof., Deptt. of Pathalogy,K.G. Medical University, Lucknow, Uttar Pradesh

Dr. Kusum Lata Mishra, In-charge, Coagulation Laboratory, Deptt. of Pathology, K.G. Medical University, Lucknow, Uttar Pradesh

Prof.(Dr.)V.K. Sharma, Prof., Deptt. of Chemistry, Lucknow University, Uttar Pradesh

Prof.(Dr.) R.K. Shukla Prof., Deptt. of Physics, Lucknow University, Lucknow Uttar Pradesh

Prof.(Dr.)Anil Gaur Prof., Deptt. of Biotechnology & Genetic Engg., G.B. Pant University of Agr. & Technology, Pant Nagar, Uttarakhand

Dr. S.P. Shukla Prof. , Deptt. of Civil Engg., Institute of Engg. & Technology, Sitapur Road , Lucknow, Uttar Pradesh

Dr. Ajay Mishra Associate Prof. , Deptt. of Geology, Lucknow University, Lucknow , U. P.

Dr. Ashutosh Singh Prof., Deptt. of Chemistry,Saket P.G. College, Ayodhya, Faizabad, U. P.

Dr. S.K. Singh Principal, Gita College of Education , Nimbari, Panipat, Haryana

Shri Sudesh Bhat Advisor (Education), Sky Institute, Lucknow, Uttar Pradesh

Dr. Krishna Gopal Asst. Prof., Deptt. of English,Rama University, Kanpur, Uttar Pradesh

Dr. Chandra K. Dixit

Dr. Mahesh Pal

Department of Physics Professor &Dean, Faculty of Science & Technology

Principal Scientist ,Phytochemistry Division, CSIR- National Botanical Research Institute, Lucknow, Uttar Pradesh

Dr. Shakuntala Misra National Rehablitationuniversity,Lucknow Professor (Dr.) Vivek Mishra Director, ITM School of Management,Lucknow,U.P.,India Anuj Kumar Gupta Assistant Professor, ITM School of Management,Lucknow,U.P.,India

Dr. Vinod Singh Assoc. Prof. & Head, Deptt. of Microbiology, Baruktulla University, Bhopal, M.P.

Dr. Anchal Srivastava, Prof., Deptt of Physics, Lucknow University,Lucknow, Uttar Pradesh

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International Journal of Scientific and Innovative Research 2017; 5(2) P‐ISSN 2347‐2189, E‐ ISSN 2347‐4971

ABOUT EDITOR-IN- CHIEF : DR. B. R. PANDEY Dr. B. R. Pandey is a well-known academician and scientist with brilliant academic career and research accomplishments. He has done M.Sc. (organic chemistry) from Banaras Hindu University, Varanasi, India in the year 1972. He has done PhD in Medicinal Chemistry under the guidance of world renowned Biochemist & Medicinal Chemist, Professor S.S. Parmar, Professor of Medicinal Chemistry & Chemical Pharmacology, Department of Pharmacology & Therapeutics, K. G. Medical College, Lucknow (Presently K. G. Medical University), Faculty of Medicine, University of Lucknow, Lucknow, India in the year 1976. Dr. Pandey has all throughout first class educational qualifications and his research interest covers medicinal chemistry, biochemical pharmacology, neurochemistry, neuro-toxicology, environmental chemistry, herbal medicine & natural products. He is having extensive research experience of more than 40 years and published several research papers in peer reviewed journals of international repute. His research particularly on the studies of central nervous system acting drugs and anti-inflammatory drugs and their biochemical mode of action using animal models and enzymes such as monoamine oxidase, acetylcholine esterase, purine catabolizing enzymes , proteolytic enzymes, membrane stabilizing enzymes, respiratory enzymes, microsomal enzymes etc. has been well recognized as evidenced by his research publications. Further, his research on developing herbal medicines has been found very useful in prevention and treatment of chronic diseases and other refractory diseases for which modern system of medicine have no permanent cure. He has worked on the position of Joint Director, Council of Science & Technology, U.P., Lucknow, Department of Science & Technology, Uttar Pradesh Government, India from the year 1979 to 2011, where he successfully executed several R & D projects in various disciplines of Science & Technology including chemical & pharmaceutical sciences, medical sciences, biological sciences, environmental sciences etc. During his tenure as Joint Director, he has been instrumental in launching and implementing important schemes: Young Scientists Scheme, Young Scientist Visiting Fellowship Scheme, Establishment of Centre of Excellence- Encephalitis Research Centre of Excellence in Sanjay Gandhi Post Graduate Institute of Medical Sciences ( SGPGIMS), Lucknow , U. P. India ; Centre of Excellence in Materials Science ( nano materials) in Z. H. College of Engg. & Technology, Aligarh Muslim University, Aligarh, U.P. India, Establishment of Patent Information Centre in the premises of Council of Science & Technology , U.P. He has also worked on the post of Secretary ( as additional charge ) , Council of Science & Technology, U.P. several times and functioned as Administrative Head of the Organization. Prior to taking over the position of Joint Director, Council of Science & Technology, U.P. in the year 1979, he has worked as Junior Research Fellow/ Senior Research Fellow (Council of Scientific & Industrial Research, New Delhi ), Assistant Research Officer ( Jawaharlal Nehru Laboratory of Molecular Biology) at Department of Pharmacology & Therapeutics, K.G. Medical College (presently K. G. Medical University), Faculty of Medicine, University of Lucknow, Lucknow, India from the year 1972 to 1979 and involved in multidisciplinary biomedical research leading to drug development . He has worked as Visiting Scientist / Faculty in the Department of Physiology, School of Medicine, University of North Dakota, Grand Forks, North Dakota, USA and also visited scientific institutions in Sweden, U.K. and U.S.A. under Training Program on Capacity Building in Environmental Research Management (World Bank Funding Project). After his superannuation in the year 2011, he has been associated with International Institute of Herbal Medicine (IIHM), Lucknow, India as Professor and is presently associated with Sky Institute, Lucknow, India as Director (Research) and Dean, Faculty of Science & Technology, Sai Nath University, Jharkhand, India and involved in programs related to higher education and research of scientific & technological fields. He has organized several national and international www.ijsir.co.in


International Journal of Scientific and Innovative Research 2017; 5(2) P‐ISSN 2347‐2189, E‐ ISSN 2347‐4971

conferences. He has actively participated in national and international conferences, symposia and workshops and presented research papers and chaired scientific / technical sessions. He is life member and fellow of many scientific societies such as National Academy of Sciences India, Society of Toxicology of India, Indian Academy of Neurosciences, Bioved Research Society India, International Society for Herbal Medicine (ISHM), Society of Biological Sciences and Rural Development, India. He has been member of several scientific expert committees/ advisory committees to evaluate scientific research proposals. Dr. Pandey has been actively associated with various universities and institutions in India as examiner for conducting graduate, post graduate and doctoral level examinations in disciplines like chemical sciences, pharmaceutical sciences, biochemical sciences, biotechnology and allied areas and member of Board of Studies for the academic development in the department. He has been approved research supervisor for guiding research in chemistry, biotechnology and related areas from various universities of India leading to PhD Degree. In view of his vast research and administrative experience and broad R & D vision, Dr. Pandey has been associated with International Journal of Scientific & Innovative Research (IJSIR) as Editor-inChief.

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International Journal of Scientific and Innovative Research 2017; 5(2) P‐ISSN 2347‐2189, E‐ ISSN 2347‐4971

CONTENTS ADVANCED MICRO AND NANO DRUG DELIVERY SYSTEM IN CANCER THERAPY Pradeep Kumar, C.K. Dixit ANTICANCER PLANTS: A REVIEW * V. Lakshmi, S.K.Agarwal and A.A.Mahdi AGING IN INSECTS: AN OVERVIEW Kalpana Singh APPLICATION OF CARBON NANOTUBE AS A GAS SENSOR Roshni Yadav and C.K.Dixit AN OVERVIEW OF ANDROGRAPHIS PANICULATA (BURM. F.) NEES Vijai Lakshmi, Santosh Kumar Agarwal and Abbas Ali Mahdi MOLECULAR DOCKING AND QSAR STUDIES OF ANTIPSYCHOTIC RISPERIDONE DERIVATIVES AGAINST SEROTON IN 5-HT2A RECEPTOR * Kiran Bhargava1, Prahlad Kishore Seth2, Kamlesh Kumar Pant1, Rakesh Kumar Dixit1and RajendraNath1 MOLECULAR DOCKING AND ADME/TOX STUDY OF NIC LOSAMIDE DERIVATIVES AGAINST NS3 HELICASE OF JEV Anjali Singh, Ajay Kumar, Vivek Srivastava EFFECT OF PLANT EXTRACTS ON MOSQUITO POPULATION K. Singh and S. Nandan FORMULATION AND EVALUATION OF POLYHERBAL OINTMENT Swapnil Dukare, Prajkta Gaikwad, Kolhe Shilpa Savata, S.L. Jadhav COMPARATIVE STUDY ON MATCHING CRITERION AND MOTION ESTIMATION OF ARRIVAL WAVES Mohit Bajpai IMPOTENCE OF COMPETENCY MAPPING INTO KNOWLEDGE MANAGEMENT Pushpendra Dixit CONTROL ANALOGUE ARRIVAL DATA USING DIGITAL VISUAL INFORMATION Mohit Bajpai SECURITY FOR DEVELOPMENT OF GPS EDUCATIONAL SYSTEM Madhulata Nirmal METHOD OF CHILDS LEARNING USING CARTOONS AND NASQL Madhulata Nirmal STEADY STATE THERMAL ANALYSIS OF DISC BRAKE ROTOR GRAY CAST IRON F12801 Hredey Mishra1, Vikas Mishra2

01 - 13

14 - 19 20 - 27 28 - 31 31 - 38

39 - 46

47 - 54

55 - 62

63 - 68

69 - 72

73 - 78

79 - 82

83 - 90

91 - 94

95 - 103


International Journal of Scientific and Innovative Research 2017; 5(2) P‐ISSN 2347‐2189, E‐ ISSN 2347‐4971

CONTENTS TRANSIENT THERMAL ANALYSIS OF DISC BRAKE ROTOR GRAY CAST IRON F12801 1 2 Hredey Mishra , Vikas Mishra THE EFFECT OF EXERTION ON HEART RATE AND RATING OF PERCEIVED EXERTION IN INDOLENT FEMALES 1 1 2 1,3 Aisha Ansari , Mohammad Shahid Ali , Jagatheesan Alagesan , *Prathap S EFFECT OF A SHORT BOUT OF EXERCISE ON CARDIORESPIRATORY CHANGES IN IDEAL WEIGHT POPULATION Mohammad Shahid Ali1, Aisha Ansari1, Jagatheesan Alagesan2, *Prathap S1,3

104 - 112

113 - 116

117 - 121


International Journal of Scientific and Innovative Research 2017; 5(2) : 1 ‐ 13 P‐ISSN 2347‐2189, E‐ ISSN 2347‐4971

ADVANCED MICRO AND NANO DRUG DELIVERY SYSTEM IN CANCER THERAPY *Pradeep Kumar, C.K. Dixit Radiation physics Laboratory, Dr. Shakuntala Misra National Rehabilitation University, Lucknow, Uttar Pradesh, India Address for correspondence: Pradeep Kumar, Radiation physics Laboratory, Dr.Shakuntala Misra National Rehabilitation University Lucknow, Uttar Pradesh, India; Email ID: pk_phyphd2016@dsmnru.ac.in ABSTRACT The diagnosis of cancer is more affected if the delivery of any drug at the right time and in the target where it is needed and it is also necessary to known the required level of drug to appreciate the full potential of therapeutic molecules. These requirementsare already more important inthe case of cancer chemotherapies due to their high toxicity which could lead to serious side effects. Polymer conjugation is also a drug delivery system in the diagnosis of cancer as well as nano and micro delivery system. Both these methods are very important to diagnosis of cancer and improved the drug administrationand the efficiency and safety of conventional chemotherapies. It also revolutionized in the pharmaceutical andbiomedical industries in cancer therapy. In this review paper we have introduced the developments in nanotechnology which offer researchers opportunities to significantly transform cancer therapies. This technology has enabled the manipulation of the biological and physicochemical competence of nanoparticles to facilitate more efficient drug targeting and delivery.This technology provides a better result than traditional method in the treatment of cancer. Keywords:Cancer; Nanotechnology; Chemotherapy; Microand Nano particles;Treatment of Cancer by Therapy method INTRODUCTION After more than a decennary of research and development, micro and nanotechnology has reshaped the tradition thinking of using material [1] for drug delivery in micro and nano range. Nano and microscale molecules are smaller than human cells by 100 to 10,000 times but are similar in size to large biomolecules such as enzymes and receptors. Nano and microscale devices are very smaller size due to this these can easily enter most cells, and those smaller than 20 nm can move out of blood vessels as they broadcast by all the body. Nano and microdevices are applicable to serve as customized, targeted drug delivery vehicles to carry large doses of chemotherapeutic agents or therapeutic genes into malignant cells while sparing healthy cells means that micro and nano drug delivery are now showing much promise for [1] numerous drug delivery application. Typically, micro and nanotechnology is dened as the use of material and system whose structures and components exhibit novel and www.ijsir.co.in

signicantly change properties when control is [1] gained at the micro and nano scale. The advanced development of drug delivery has improved therapeutic and toxicological properties of existing chemotherapies and [3] facilitated the implementation of new one. By including the drug in technologically optimized drug delivery system or conjugating the drug with different polymers, it is possible to modify the pharmacokinetics and bio-distribution of the drugs, improving the efcacy and security of the therapy.[3] In cancer treatment, micro and nano particles can further rely on the enhanced permeability and retention effect caused by leaky tumor for better drug accumulation at tumor sites. These benets have made therapeutic nanoparticles a promising condition to replace tradition chemotherapy, where intravenous injection of toxic poses a serious threat to healthy [1] tissue and result in dose limiting side effect. 1


International Journal of Scientific and Innovative Research 2017; 5(2) : 1 ‐ 13 P‐ISSN 2347‐2189, E‐ ISSN 2347‐4971

Table 1: Late 1970

Current

Future

First nanoscale drug delivery Nowdays, liposome, cream, system was lipid vesicles capsule, tablets, gel, aqueous solution, aerosols/spary delivery are used as form of delivery. Consider impossible to 15% of market uses administer the pharmaceutical nanoparticles for drug delivery suspensions by intravenous system. means due to abvious risks of embolism. CANCER Cancers are abnormal cells which are different from healthy cells because these cells divide more rapidly than healthy cells. These cells found in collective behavior. Due to this behavior they

Nano and micro enabled technology will take the maximum share of the market up nearly 90% of drug delivery market. Safe, effective and without side effect. No wastages and increased bioavailabidity are going to be basis of future drug delivery.

form a mass of tissues is called a tumor. These cancerous cells that come in excess amount cause many problems to the bodies of patients. Figure-1, which shows below, shows the difference between normal and abnormal cell.

[Source- normal cell vs. bludder cancer cell ENCOGENCOGNITIVE COM- 254*148-SEARCH BY IMAGE]Fig-1 GENETIC OF CANCER Before we know fully main issue of this report which deals with application of nanotechnology in cancer prevention, detection and treatment, we must indicate the underlying causes and the genetic mechanisms involved in cancer. Here we present an over-simplied text of what is known on the genetic of cancer for sake of brevity.[4] Cancer or neoplasm, on the other hand, aggregate tissues composed of cells that divide and grow abnormally. The intact number of geneticchanges required for these malfunctions 2

remains unresolved for any cancer, but for adult cancers believed to range from 5 to 15 nano [5] meter. The division of the abnormal cell is continues, and formed a large collection of cell. This type cluster of abnormal cells is known as a malignant tumour, and can furiously damage the surrounding tissue as it sucks up essential nutrients and displaces healthy cells.[6] Eventually, when the quantity of tumor is very large, then it creates more problems in the bloodstream and forming tumors in the other parts of body. This latest phenomenon is known as metastasis. www.ijsir.co.in


International Journal of Scientific and Innovative Research 2017; 5(2) : 1 ‐ 13 P‐ISSN 2347‐2189, E‐ ISSN 2347‐4971

Effectively, it multiplies the cancer as well as its effects and eventually will prove fatal to the patient. In the below gure-2 and gure-3, show

that how generate abnormal cell in our body and take a part of tumor which is called cancer.

[Source-CANCER CELL CANCER RESEARCH UK Cancer research UK 375*263-search by image]

Fig-2

[Source-CANCER CELL CANCER RESEARCH UKCancer research UK 375*263-search by image]

Fig -3 CHEMOTHERAPY Chemotherapy is a type of treatment for cancer. It uses special drugs to kill cancer cell in body. Chemotherapeutic proxy work by destroying rapidly dividing cells, which is the main property [17] of neoplastic cells. Chemotherapy usually assigns to the use of medicines or drugs to treatment of cancer. The goal of chemotherapy is to stop or slow the growth of cancer cells.[8, 9] Chemo drugs target rapidly growing cancer cell, but they can also affect healthy cells that grow rapidly. To remove this problem a new method is created and is called radiation therapy. In this treatment drug is not used to treat a cancer. It gives www.ijsir.co.in

a better result in comparison to other treatment. Ordinarily, chemotherapy (chemo) hand over to the use of medicines or drugs to treat cancer. Therefore chemotherapy have important role in treatment of cancer. But knowing what chemotherapy is, how it works, and what to expect can often help calm your fears. It can also give you a better sense of control over your cancer treatment. [10] 1. How is Chemotherapy Used to Treat Cancer? Chemotherapy is most impotent method for drug in treatment of any disease.

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Chemotherapeutic agents work by destroying rapidly dividing cells, which is the main property of neoplastic cells. But mostly people think that chemotherapy is used for drugs in cancer [17] treatment. It's often shortened to “chemo.” Surgery and radiation therapy are also treatment methodsfor cancer, remove and kill, or damage cancer cells in a certain area, but chemo can work throughout the whole body. This means chemotherapy can kill cancerous cells that have elaboration (metastasized) to parts of the body far away from the original (primary) tumor. 2. Goals of chemotherapy treatment The main goals for chemotherapy (chemo) in cancer treatment are three types which are following: 1. Cure 2. Control 3. Palliation 2.1. Cure Normally chemotherapy destroyed the cancerous cell – it goes away and doesn't come back. But tradition method doesn't promiseto prevention, diagnosis and treatment of cancer therefore many doctors don't use the word “cure” except as a possibility or intention. So, when giving treatment that has a chance of remedying a person's cancer, the doctor may describe it as treatment with curative occasion.There are no guarantees, and though cure may be the goal, it doesn't always work out that way. It often takes many years to know if a person's cancer is really cured. 2.2. Control When the treatment (cure) of cancer is not possible then the goal may be to control the disease. Chemo is used to shrink tumors and/or stop growing and spreading of cancer cells. Therefore it can help the person with cancer feel better and live longer. 2.3. Palliation Chemotherapy can also be used torepel symptoms caused by the abnormal cells indite. This is called palliative chemotherapy or palliation. When cancer is in the last stage ie advanced stage, meaning that it is not under control and abnormal cells has spread from where it started to other parts of the body. In this condition the goal may be to improve the quality of life or help the person feel 4

better. For instanter, chemo may be used to help shrink a tumor that's causing pain or pressure. 3. Limitations of conventional chemotherapies Chemotherapy is one of the main important method for treatment of cancer but it has high toxicity due to this it has some drawback, which is proved harmful on the human body of cancer patients, which could lead to serious side effects,reducing the administrable and the therapeutic effect and the main drawback of conventional chemotherapy is that healthy cell are also affected because it cannot give selective action only to the cancerous cells.[18,19] Traditional chemotherapeutic agents often get washed out from the circulation being devoured by macro and nano phase. Cancerous cell are not totally effective by chemotherapy because the circulation of chemotherapeutic agents for a very short time and cannot interact with the cancerous cells. The major drawback behind the failure of traditional chemotherapy is the poor solubility of [20] the drugs. Therefore the administered drugs remain unsuccessful or cannot bring the desired [21–22] output. In this review paper weare addressingthat the treatment of cancerous cell is possible by nano and micro drug delivery in chemotherapy which is more effectively than traditional chemotherapy. To improve the output for treatment of cancer it is essential to transport the therapeutically active molecule mainly to the target where it is needed and at therequired time and level.[10] This could be achieved by embedding the drugs into nontoxic and biodegradable polymers from which the drug [11] will be released in a sustained manner. RADITION THERAPY One of the most common treatments for cancer is Radiation therapy. It uses high-energy particles or waves, such as x-rays, gamma rays, electron beams, or protons, to destroy or damage cancer cells. Other names for radiation therapy are radiotherapy, irradiation, or x-ray therapy. [28] Radiation can be used or used with other treatments, such as surgery or chemotherapy. In fact, denite drugs are known to be radio sensitizers (RAY-dee-oh-SENS-it-tie-zers). This means they can actually make the cancer cells more sensitive to radiation, which helps the radiation to better kill cancer cells.[28] www.ijsir.co.in


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Examples of different drug delivery approaches that are FDA-approved or are in clinical development as anti cancer treatments. Reproduced from Moses et al, 2003 with kind permission from Cancer Cell. Figure 4 MICRO AND NANO - TECHNOLOGIES The dreadful opportunities exist for using micro and nanoparticles as controlled drug delivery systems for cancer treatment.[32]The term “microparticle” refers to a particle with a diameter of 1- 1000 mm, while “nanopaticle” is used when the particle is <1 mm in size. However, under this term it is possible to distinguish several reservoirs including micro/nanocapsules, micro/nano spheres, liposomes, etc. All these devices differ www.ijsir.co.in

not only in the structure (Figure 5) but also in their biopharmaceutical cretic and therapeutic uses . [33]The manufacturing protocol of each molecule differs also considerably and the scale-up could be a challenge for some of these devices. An important issue to be considered when manufacturing these systems is the drug load that the reservoir can carry. This drug load depends on the size and the structure of the device, ranging from some few molecules of the drug to a few 5


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tens. Therefore, selection of drugs with potent pharmaceutical activity is necessary in order to have therapeutic effects in the released dose. Furthermore, it is essential that the drug will not be altered during the fabrication process and the storage. Finally, interactions between drug and the reservoir must be optimized to facilitate drug release only in the target where it is needed and at the desired kinetic-release. Natural and synthetic polymers including albumin, brinogen, alginate, chitosan and collagen have been used for the structure of micro and nanoparticles. However, among all of them, lactic-glycolic acid copolymers are the most frequently employed materials due to their biocompatibility and biodegradability. Following a multiple emulsion process, a drug can be entrapped into a poly (lactic-co-glycolic) (PLGA) microsphere and released at a zero-order kinetic by diffusion of the drug through the polymer reservoir and the slow degradation of the polymer matrix. These advantages resulted in the rst two PLGA

6

microparticle extended-release formulations that were approved by the US Food and Drug Administration (FDA). One of themreleased the ] recombinant humangrowth hormone (rhGH) whereas the other microparticle-based drug delivery system released the euteinizinghormone-releasing hormone (LHRH) agonist [34] leuprorelin acetate. The latter is currently on the market under the name of Lupron® Depot and it is approved in the United States for the palliative treatment of advanced prostate cancer. However, there are still few microencapsulated structure on clinical trials addressing cancer treatments. In fact, a recent review of National Cencer Institute revealed that from the 1200 open clinical trials in the United States only one to be testing a microparticulate system for controlled drug [35] delivery. Experts, however, predict that within the next 5-10 years some of the structure currently understudy might progress to the clinical evaluation and perhaps become marketed therapy [36] not so far.

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Schematics of different nano technology based drug delivery systems for cancer therapy. Reproduced from Sahoo and Labhas et.war, 2003 with kind permission from Drug Discovery Today. Figure 5: Although the total drug-load is reduced considerably and the manufacture process is more complex, the nano-scale devices present some advantages over the micro-systems. In fact, submicron systems show higher intracellular uptake than microsized particles, thereby allowing drug-release in different cellular compartments such as cytoplasm and nucleus. Nanoparticles can be also easily conjugated with a ligand to favour a targeted therapeutic approach and as it has been reported, some nanoparticles can cross the blood-brain barrier (BBB). For example, doxorubicin bound to polysorbatecoated nano-particles can cross the intact BBB, www.ijsir.co.in

reaching therapeutic concentrations in the brain. When these particles were administered in gliobla-stoma-bearing rats, a very aggressive human cancer with short survival times, signicantly higher survival times were observed in the treated animal group compared with all [37] other groups. Depending on the elaboration method and the materials employed different nanosystems can be distinguished including micelles, nano-capsules, dendrimers, nanospheres, solid lipid nano particles and ceramic nano-particles. The principal characteristics and some of the recent research using eachnanosystems is reviewed in Table 2. 7


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Table 2: Examples of different nanoparticles and their applications as cancer treatments Nanoparticle

Description

Recent applications

Reference

Nanocapsules

Vesicular systems in which the drug issurrounded by a polymeric membrane

Stability of the cisplatin nanocapsules has been optimized by varying the lipidcomposition of the bilayer coat Bovine serum albumin nanospheres containing 5 uorouracil show higher tumourinhibition than the free drug Micelle delivery of doxorubicin increasescytotoxicity to prostate carcinoma cells Ultra ne silica based nanoparticles releasingwater insoluble anticancer drug Radiation - guided drug delivery of liposomal cisplatin to tumor blood vessels results inimproved tumour g rowth delay Targeted delivery within dendrimers improved the cytotoxic response of the cells tomethotrexate 100 - fold over free drug SLN powder formulation of all - trans retinoicacid may have potential in cancerchemoprevention and therapeutics.

Velinova al. 2004

Nanospheres

Matrix systems in which the drug is physically and uniformly dispersed

Micelles

Amphiphilic block copolymers that canself associate in aqueous so

Ceramic nanoparticles Liposomes

lution

Nanoparticles fabricated using inorganiccompounds including silica, titania… Articial spherical vesicles producedfrom natural phospholipids andcholesterol

Dendrimers

Macromolecular compound thatcomprise a series of branches around aninner core

SLN particles

Nanoparticles made from solid lipids

Nano-technology can be used for more efcient drug delivery system to tumor. Nano-particles can control the basic functions of cells, and potentially kill cancer cells, by virtue of their size alone without the need for drugs. One of the important mission of passive lipo-somal drug delivery is to cancer. Lipo-somes are one of the most well-known drug delivery carriers employed in the treatment of cancer. Due to their advantages, lipo-somal formulations provide a substantial increase in anti-tumor efcacy comparing with the free drug or standard chemotherapy regimens. [38] Liposomes are composed of a double lipid bilayer which encloses an aqueous space that can be employed to transport anticancer drugs. The shape of liposome is a spherical vesicle having at least one lipid bilayer. Liposome can be used as a administration of nutrients and pharmaceutical drug. Liposomes are nanoparticles ranging from 20 nm to 500 um in 8

et [39]

Santhi, et al. 2002 [4 0 ]

McNaealy, al. 2004 [41]

et

Roy, et al. 2003

[42]

Geng, et [43] al. 2004

Quintana, et al. 2002 [44]

Soo - Jeong, et al. 200 4 [4 5 ]

diameter. They are small spheres, the wall that separates the internal media from the external environment is a lipid bilayer. Given that they are comprised of both a lipid fraction and an aqueous fraction, liposomes can incorporate lipophilic [30] substances and hydrophilic substances. Figure 6 schematically shows liposomes with the two types of load. Nanotechnology can be used for more efcient drug delivery system to tumor. Nanoparticles can control the basic functions of cells, and potentially kill cancer cells, by virtue of their size alone without the need for drugs. One of the important mission of passive liposomal drug delivery is to cancer. Lipo-somes are one of the most well-known drug delivery carriers employed in the treatment of cancer. Due to their advantages, lipo-somal formulations provide a substantial increase in anti-tumor efcacy comparing with the free drug or standard [39] chemotherapy regimens. Liposomes are www.ijsir.co.in


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composed of a double lipid bilayer which encloses an aqueous space that can be employed to transport anticancer drugs.The shape of liposome is a spherical vesicle having at least one lipid bilayer. Liposome can be used as a administration of nutrients and pharmaceutical drug. Liposomes are nanoparticles ranging from 20 nm to 500 um in diameter. They are small

spheres, the wall that separates the internal media from the external environment is a lipid bilayer. Given that they are comprised of both a lipid fraction and an aqueous fraction, liposomes can incorporate lipophilic substances and hydrophilic substances. [30] Figure 6 schematically shows liposomes with the two types of load.

[Source-http://www.lipomize.com/en/liposome] Figure6 Liposome molecules are easily diffused into the cells, since their structures and cell membrane structure can interact very well while drug uptake process. The enhanced permeation and retention (EPR) effect is the concept that liposomes remain in the bloodstream for a long time and are collected passively from tumor cell. Through the

EPR effect, concomitant in toxicity problem of therapy is relatively solved as lower and repeated dose of liposome drug. The uses of EPR effect allow up to 10 times the amount of drug to be delivered to the tumor than the free drug method.[31] The characterization of liposome molecule is give in g.7

Source- liposomes as as potential drug carrier system Intech-760*456-search by image ] www.ijsir.co.in

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In the below gure no 8, we are addressing the process of working of nanoparticle drug delivery

to target the tumor and the way how can remove the tumor and controlled the abnormal cell.

[Source-http://pubs.acs.org/doi/abs/10.1021/nn900002m]

Figure 8

10

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CONCLUSION Buy reviewing of this article, it is clear that “nanotechnology is the key word of human life.” Every eld is affected by the nanotechnology. Nanotechnology changes the denition of many object and has already revolutionized cancer therapy in many aspects and is radically changing the treatment pattern. Nanotechnology gives a better result in the treatment of cancer.Nowadays the treatment of cancer is very easily available in comparison to past time. The treatment of cancer by traditional method is very harmful for patient, but by nano and micro drug delivery in therapy, it is harmless. There are more advantages in the treatment of cancer. The present paper reviews the use of micro and nanotechnology as well as macromolecular conjugation as strategies to deliver existing chemotherapies and novel therapeutic molecules in a controlled manner to malignancies. These technologies come along with other exciting drug delivery approaches such as patches, microchips and osmotic pumps. In general, the technologies described here improve signicantly the pharmacokinetics and biodistribution of the free drugs and reduce considerably their side-effects.

3.

4.

5.

6.

7.

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Cancer Chemother Pharmacol 44,178-179” 10. https://www.cancer.org/treatment/treatmentsand-side-effects/treatment-types/ chemotherapy.html 11. Orive G, Hernández RM, Gascón AR, Calaore R, Chang TMS, De Vos P, Hortelano G, Hunkeler D, Lacík I, Shapiro AMJ, Pedraz JL (2003c) “Cell encapsulation: promise and progress”. Nat Med 9, 104-107. 12. Duncan R (2003) “ The dawning era of polymer therapeutics”. Nat Rev Drug Discov 2, 347- 360. 13. Theodolou M, Clifford H (2004) “Cardiac proles of liposomal anthracyclines: greater cardiac safety versus conventional doxorubicin? Cancer” 100, 2052-2063. 14. Maeda H, Wu J, Sawa T, Matsumura K, Hori K (2000) “ Tumor vascular permeability and t h e E P R e ff e c t i n m a c r o m o l e c u l a r therapeutics: a review” J Control Rel 65, 271-284. 15. Jain, RK (2001) “Normalizing tumor vasculature with antiangiogenic therapy: a new paradigm for combination therapy”. Nat Med 7, 987-989. 16. Northfelt DW, Martin FJ, Working P, Volberding PA, Russell J, Newman M, Amantea MA, Kaplan LD (1996)” Doxorubicin encapsulated in liposomes containing surface-bound polyethylene glycol: Pharmacokinetics, tumor localization, and safety in patients with AIDS-related Kaposi's sarcoma.” JClin Pharmacol 36, 55-63. 17. G. Zhao and B. L. Rodriguez, “Molecular targeting of liposomal nanoparticlesto tumor microenvironment,” International Journal of Nanomedicine, vol. 8, pp. 61–71, 2013. View at Google Scholar 18. K. T. Nguyen, “Targeted nanoparticles for cancer therapy: promises and challenges,” Journal of Nanomedicine & Nanotechnology, vol. 2, no. 5, article 103e, 2011. View at Publisher · View at Google Scholar 19. A. Coates, S. Abraham, and S. B. Kaye, “On the receiving end—patient perception of the side-effects of cancer chemotherapy,” European Journal of Cancer and Clinical Oncology, vol. 19, no. 2, pp. 203–208, 1983. View at Google Scholar · View at Scopus: 12

20. S.A. Mousa and D. J. Bharali, “Nanotechnology-based detection and targeted therapy in cancer: nano-bio paradigms and applications,” Cancers, vol. 3, no. 3, pp. 2888–2903, 2011. View at Publisher · View at Google Scholar · View at Scopus 21. R. Krishna and L. D. Mayer, “Multidrug resistance (MDR) in cancerMechanisms, reversal using modulators of MDR and the role of MDR modulators in inuencing the pharmacokinetics of anticancer drugs,” European Journal of Pharmaceutical Sciences, vol. 11, no. 4, pp. 265–283, 2000. View at Publisher · View at Google Scholar · 22. View at ScopusM. E. Davis, Z. Chen, and D. M. Shin, “Nanoparticle therapeutics: an emerging treatment modality for cancer,” Nature Reviews Drug Discovery, vol. 7, no. 9, pp. 771–782, 2008. View at Publisher · View at Google Scholar · View at Scopus 23. Levy Y, Hersheld MS, Fernandez C, Polmar SH, Scudiery D, Berger M, Sorensen, RU (1988) Adenosine deaminase deciency with late onset or recurrent infections: response to treatment with polyethylene glycol modied adenosine deaminase. J Pediatr 113, 312-317. 24. Iakoubov L, Rokhlin O, Torchilin V (1995) Antinuclear autoantibodies of the aged reactive against the surface of tumor but not normal cells. Immunol Lett 47, 147-149. 25. Zhang Y, Guo L, Roeske RW, Antony AC, Jayaram HN (2004) Pteroyl- -glutamatecysteine synthesis and its application in folate receptor-mediated cancer cell targeting using folatetethered liposomes. Anal Biochem 332, 168-177. 26. http://hcp.zoladex.net/Article/501611.aspx 27. http://www.clevelandclinic.org/myeloma /pegasp.htm 28. h t t p s : / / w w w. c a n c e r. o r g / t r e a t m e n t / treatments-and-side-effects/treatmenttypes/radiation/radiation-therapy-guide /what-is-radiation-therapy.html 29. http://pubs.acs.org/doi/abs/10.1021/nn 900002m 30. http://www.lipomize.com/en/liposome 31. Sengupta S, Sasisekharan R (2007) Exploiting nanotechnology to target cancer, Br J Cancer 96: 1315-1319 www.ijsir.co.in


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32. Panyam J, Labhasetwar V (2003) Biodegradable nanoparticles for drug and gene delivery to cells and tissue. Adv DrugDeliv Rev 55, 329-347. 33. Orive G, Hernández RM, Gascón AR, Domínguez-Gil A, PedrazJL (2003b) New approaches in the delivery ofbiophar maceuticals. Trends Pharm Sci 25, 382-387. 34. Cleland JL (1997) Recombinant human growth hormonepoly (lactic-co-glycolic acid) micro-sphere for-mulation development. Adv Drug Deliv Rev 28, 7184. 35. Birnbaum DT, Brannon-Peppas L (2004) Microparticle drugdelivery systems. In Drug delivery systems in cancer therapy,Ed. Brown DM, Humana Press, 117-135. 36. Hedley ML, Curley JM, Langer RS (1998) Microparticles for delivery of nucleic acid, USA Patent 5783567, July 21; assigned to Pangaea Pharmaceuticals. 37. Steiniger SCJ, Kreuter J, Khalansky AS, Skidan IN, Bobruskin AI, Smirnova ZS, Severin SE, Uhl R, Kock M, Geiger KD, Gelperina SE (2004) Chemotherapy in rats with doxorubicinloaded nanoparticles. Int J Cancer 109, 759-767. 38. Drummond DC, Kirpotin D, Benz CC, Park JW, Hong K (2004) Liposomal drug delivery systems for cancer therapy In Drug delivery systems in cancer therapy, Ed. Brown DM, Humana Press, 191-213. 39. Velinova MJ, Staffhorst RW, Mulder WJ, Dries AS, Jansen BA, de Kruijff B, de Kroon AI.Preparation and stability of lipid-coated nanocapsules of cisplatin: anionic phospholipid specicity.Biochim Biophys Acta. 2004 May 27;1663(1-2):135-42. 40. Santhi K., Dhanaraj S. A., Joseph V.,

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Ponnusankar S., Suresh B. A study on the preparation and anti-tumor efcacy of bovine serum albumin nanospheres containing 5-uorouracil. Drug Dev. Ind. P h a r m . 2 0 0 2 ; 2 8 : 11 7 1 – 11 7 9 . d o i : 10.1081/DDC-120014584 41. McNealy TL, Trojan L, Knoll T, Alken P, Michel MS. Micelle delivery of doxorubicin increases cytotoxicity to prostate carcinoma cells. Urol Res. 2004 Aug;32(4):255-60. Epub 2004 Jan 9. 42. Indrajit Roy,Tymish Y. Ohulchanskyy, Haridas E. Pudavar, Earl J. Bergey, Allan R. Oseroff, Janet Morgan, Thomas J. Dougherty, and Paras N. Prasad Ceramic-Based Nano-particles Entrapping Water-Insoluble Photo-sensitizing Anti cancer Drugs: A Novel Drug−Carrier System for Photo-dynamic Therapy. J. Am. Chem. Soc.,2003, 125 (26), pp 7860–7865

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Radiation-guided drug delivery of liposomal cisplatin to tumor blood vessels results in improved tumour growth delay. Geng, 2004Nanotechnology Update Nanomedicine – Fighting Cancer, 44. Quintana A, Raczka E, Piehler L, Lee I, Myc A, Majoros I, Patri AK, Thomas T, Mulé J, Baker JR Jr. Design and function of a dendrimer-based therapeutic nano-device targeted to tumor cells through the folate receptor. Pharm Res. 2002 Sep;19(9):13106. 45. Soo-Jeong Lim, Mi-Kyung Lee, ChongKook Kim, Altered chemical and biological activities of all-trans retinoic acid incorporated in solid lipid nanoparticle powders. DOI: 10.1016/j.jconrel. 2004.07.032

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ANTICANCER PLANTS: A REVIEW *

V. Lakshmi, S.K.Agarwal and A.A.Mahdi

Department of Biochemistry, King George's Medical University, Lucknow, Uttar Pradesh, India *Address for correspondence: Dr.Vijai Lakshmi, Emeritus Scientist, Department of Biochemistry, King George's Medical University, Lucknow, U.P. , India Email ID: vijlakshmius@yahoo.com ABSTRACT Over the last 4-5 decades, biologically active compounds derived from natural resources have provided a number of useful cancer chemotherapeutic drugs. The search for natural products based drug candidates is growing rapidly with the advancements in drug discovery and development techniques in recent years, with the active fractions and isolates of marine organisms along with terrestrial plants and microorganisms. The present review highlights the information about occurrence of such promising leads from natural origin tend to create extensive interest among researchers including medicinal chemists and pharmacologists working in anticancer drug research and therefore the availability of a given brief information about cancer and anticancer drug development focused on natural products. Keywords: Anticancer; Medicinal Plants. INTRODUCTION Cancer is responsible for about 25% deaths caused due to diseases in the developed countries and is a major public health burden and challenge for world health organization and research [1-3] organizations. It is considered as an adversary of industrial revolution followed by advanced pattern of socio-cultural life dominated by excessive intake of exogenous chemicals and less physical activities. The number of incidences of different types of cancers is also increasing in developing countries, as the extensive technical advancements in the field of drug development and other areas allowed their populations live longer and make negative lifestyle changes leading to increased risk of cancer. Cancer is a broad group of diseases characterized primarily by uncontrolled cell division leading to increase in the number of malignant cells in a tissue, invasion of adjacent tissues by malignant cells, or spread of malignant cells through lymphatic or circulatory system to regional lymph nodes and distant tissues (metastasis). It develops through multi-step process that initiates with small preneoplastic changes, which may subsequently progress to neoplasiab. [ 4 , 5 ] Under certain conditions, neoplastic cells escape the host's 14

immune surveillance that helps to develop the capacity of growth, invasion and metastasis. Cancer cells behave as independent cells and proliferate continuously with out growth regulation, leading to tumor development through multi step process. An ideal anti cancer drug would restore normal growth regulation and cell cycle control to cancer cells through restoring aberrant molecular signaling pathways and inducing apoptosis in these cells. It should selectively target different components of physiological and biochemical pathways related to different stages of cancer development without affecting the normal cells. The discovery of new compounds with novel mechanisms of action, contribute to improved and highly effective methods for cancer treatment. A newer dimension in the anticancer drug research is the increasing awareness about natural products based chemotherapy. Several studies have demonstrated that different plant-based foods such as onion, grapes, garlic, ginger, soybean, turmeric, cabbage, cauliflower, broccoli and tomato can offer significant anticancer potential. Natural products have provided four important categories of antitumor agents: taxanes, www.ijsir.co.in


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camptothecins, bisindole alkaloids also known as vinca alkaloid and epipodophyllotoxins. Micro organisms have also provided several potent anti cancer drugs in form of anti cancer antibiotics such as doxorubicin, actinomycin and mitomycin C. A natural product is a chemical compound or substance produced by a plant, animal or microorganism and usually has a pharmacological or biological activity which can be utilized in pharmaceutical drug discovery and drug design. Chemically natural products are secondary metabolites, specifically produced by a particular group of organisms and have been postulated to play an important role in self defense against predators as well as in interspecies interactions. Their role is exceptionally pronounced in the field of anti cancer drug research. ...... 1 Roughly 50 % of the new chemical entities introduced during last three decades were either natural products or derived from natural products through structural modifications. Due to enormous advancement in the field of medicinal chemistry, design of natural product or natural product-mimetic scaffolds can be achieved readily in one-step with the help of multi component reactions. Usually, natural products are isolated only in minute amounts and thus subsequent techniques are required to scale-up of the biologically active molecules. With reference to above facts, the review has been designed to cover the history of drug development from natural resources, anticancer compounds isolated from different natural resources. TYPES OF CANCER Based on the histological characteristics hundreds of different cancers have been identified, which can be classified into six major groups. 1.Carcinomas Cancers caused due to alteration in epithelial cells covering the surface of skin and internal organs are termed as carcinomas. It is the most common type of cancers, predominantly occurring in the old age, for example breast, prostate, lung, pancreas, and colon cancers. Carcinomas, account for 80 to 90 percent of all cancer cases. These can be further divided into two major subtypes: (i) Squamous cell carcinoma, which www.ijsir.co.in

develops in the squamous epithelium and (ii) adenocarcinoma, which develops in an organ or gland. 2. Sarcomas Cancers arising on different connective tissue including bone, cartilage and nervous system are termed as sarcomas. These are known to develop from cells originating in mesenchyma outside the bone marrow. Most important examples of sarcoma include fibro sarcoma (fibrous tissue), rhabdomyosarcoma (skeletal muscle), angiosarcoma or heman gioendo the lioma (blood vessels), glioma or astrocytoma (neurogenic connective tissue found in the brain) mesothelial sarcoma or mesothelioma (membranous lining of body cavities) 3. Myelomas These include the cancers arising in the bone marrow plasma cells. These are also called cancers of antibody producing white blood cells 4. Lymphomas These are developed in the lymph glands and other organs of lymphatic system including tonsils, thymus gland and spleen playing active role in immune system. Lymphomas may also occur in some other organs including breast, stomach and brain. Lymphomas occurring in t h e s e o rg a n s a r e k n o w n a s e x t r a n o d a l lymphomas. These can be further divided into two major subtypes: (i) Hodgkin lymphomas and (ii) non- Hodgkin lymphomas. Both of these subtypes can be differentiated on the basis of the presence of reed-sternberg cells in Hodgkin lymphoma. 5. Leukemias The cancers occurring in bone marrow are termed as leukemia. It results in the overproduction of immature white blood cells (WBC) rendering the patients immunodeficient and susceptible to subsequent infections. In some cases it also affects red blood cells (RBC) and platelets leading to anemia as well as defective blood clotting. The important examples of leukemia include chronic myelocytic leukemia (CML) occurring in adults, acute myelocytic leukemia (AML) occurring in children, chronic lymphocytic, lymphatic, or lymphoblastic leukemia (CLL) common in adults, acute lymphocytic, lymphatic, or lymphoblastic leukemia (ALL) common in children and adults. 15


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6. Mixed Types These comprises of more than one component which may be within one category or from different categories. Examples of mixed type include adenosquamous carcinoma, mixed mesodermal tumor, carcinosarcoma and teratocarcinoma. NATURAL PRODUCTS AS SOURCE OF THE RAPEUTIC AGENTS The Mother Nature has been continuously serving the mankind as most efficient arsenal, playing an important role in health care and prevention of diseases. Natural products have traditionally been used in form of plant extracts, dry powders, infusions, or other therapeutic preparations to treat several diseases over centuries and continue to play a highly significant role in the modern drug discovery and development process providing a diverse and unique source of medicinally active molecules. Medicinal plants play a major role and constitute the backbone of almost all the traditional systems of medicine. Ayurveda, known as the science of life is one of the oldest system of medicines. This system of using natural resources for betterment of health was originated in India long ago in the pre-Vedic period through day by day experiences and experimentations with the aim of maintaining health and treatment of various diseases. Several other systems of complementary and alternative medicines including Siddha and Unani are also developed from plant based formulations through experience and interactions with natural resources. The earliest written evidence related to use of plant products as therapeutic agents is available on Atharvaveda, one of the four most ancient books of knowledge and culture related to Hindu religion showing the strength of Indian wisdom. As many as 114 different therapeutic formulations have been described for the treatment of different diseases. The therapeutic importance of Indian medicinal plants has been exposed thoroughly in the Susruta samhita and Charaka samhita during the Vedic period. Indian Materia medica has description of more than 2000 drugs derived from natural resources most of which are originated from different systems of traditional and folk practices. 80 % of these drugs are of plant origin whereas the rest are minerals or 16

animal products.Indian medicinal plants possess enormous therapeutic potential but only a small proportion of it has been explored by mankind leaving the great opportunity to discover novel drugs from natural origin. Numerous therapeutic preparations have been developed by traditional healers and Ayurvedic practitioners for the treatment of various disorders and diseases. Subsequently after the emergence of natural product chemistry thousands of new medicinal plant were identified with immense therapeutic potential. Natural Products chemistry together with analytical chemistry, spectroscopy, pharmacology, biochemistry and other related disciplines demonstrated its value for drug development. It has not only enriched modern medicine with novel bio-active molecules but also provided valuable leads for drug designing. Since the isolation of morphine from Papaver somniferum in 1806, extensive efforts are being done to isolate therapeutically active molecules from medicinal plants. Some important examples 3 include emetine, colchicine, atropine,........... cocaine, ephedrine and quinidine. BIOASSAY GUIDED DRUG DISCOVERY Bioassay-directed fractionation supported by several recent techniques is extensively used to identify the active principles/pure compounds present in crude natural products preparations. This approach can be used systematically to reduce the complexity of the extracts/fractions in order to locate the biological activities of complex materials. It resolves the complex mixtures to [6,7] more simple and pure form. Considering on therapeutic preparation obtained from crude extracts, only a specific portion of the extract-the active principles/bioactive molecules with specific biological targets is of interest. In view of this fact, a bio-molecular interaction step should be included into analytical methods to achieve bio-selectivity and to purify the compounds with specific therapeutic activity. POTENTIAL ANTICANCER AGENTS OBTAINED FROM NATURAL PRODUCTS Citrus fruits and green vegetables provide a rich source of vitamins, flavonoids and other polyphenolic compounds, adequate consumption of these plant products reduce the risk of cancer. www.ijsir.co.in


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More than 1,000 non-nutritive plant derived compounds are known to have cancer-preventive activity. More than 400 plant derived compounds with anticancer potential are under investigation. . Most of the species of higher plants, microorganisms, arthropods, and marine invertebrates are still not studied and thus these

diverse natural resources can be explored to provide novel anticancer agents. Recent studies have identified new species of bacteria, algae, fungi, and vertebrates which are able to provide new anticancer molecules. Some important medicinal plants possessing anticancer potential are listed in table 1.

Table 1: Some important Medicinal Plants possessing anticancer activity Plant name

Family

Active part

Plant name

Family

Active part

Acacia xanthophloea

Leguminosae

Fruit

Ipomea batata

Convolvulaceae

Rhizome

Adenium obesum

Apocyn

Leaf

Juncus acutus

Juncaceae

Leaf

Adiantum macrophyllum

Pteridaceae

Entire

Lannea stuhlmannii

Anacardiaceae

Root

Aeonium arboretum

Crassulaceae

Leaf

Lavandula angustifolia

Meliaceae

Leaves

Aglaia foveolata

Meliaceae

Fruit

Lep tadenia hastate

Asclepiadaceae

Bark

Alnus japonica

Betulaceae

Wood

Ligustrum lucidum

Oleaceae

Seed

Aphanamixis polystachya

Meliaceae

Stem bark

Maytenus canariensis

Celastraceae

Fruit juice

Arisaema erubescens

Araceae

Root

Ma ytenus macrocarpa

Celastraceae

Stem bark

Aster amellus

Compositae

Entire

Maytenus serrata

Celastraceae

Seed

Azadirachta indica

Meliaceae

Leaf

Monnina obtusifolia

Polygalaceae

Aerial parts

Begonia glabra

Begoniaceae

Entire

Morinda ci trifolia

Rubiaceae

Root

Carapa guianensis

Meliaceae

Seed oil

Ocotea foetens

Lauraceae

Branchlets

Cassia quinquangulata

Caesalpiniaceae

Root

Pinus parviflora

Pinaceae

Strobilus

Celastrus orbiculatus

Celastraceae

Entire

Piper latifoli um

Piperaceae

Leaf

Crassocephalum bojeri

Compositae

Entire

Plantago asiatica

Plantaginaceae

Leaf

Combretum caffrum

Combretaceae

Bark

Pleione bulbocodioides

Orchidaceae

Tuber

Cyathea fauriei

Cyatheaceae

Shoot

Pratia nummularia

C ampanulaceae

Entire

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aceae

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Dillenia suffruticosa

Dilleniaceae

Fruit

Phymatosorus diversifolium

Polydiaceae

Root

Dioscorea collettii

Dioscoreaceae

Rhizome

Phytolacca esculenta

Phytolaccaceae

Root

Dysosma pleiantha

Berberidaceae

Root

Rabdo sia rubescens

Labiatae

Leaf

Caragana cuneata

Leguminosae

Leaf

Ruellia tuberose

Acanthaceae

Bark

Croton flavens

Euphorbiacaeae

Leaf

Salvia chinensis

Labiatae

Entire

Croton lechleri

Euphorbiacaeae

Latex

Salvia officinalis

L abiatae

Leaves

Cynanchum hancoekianum

Asclepiadaceae

Entire

Scirpus holoschoenus

Cyperaceae

Inflorescence

Deeringia amaranthoides

Amaranthaceae

Fruit

Scutellaria barbata

Labiatae

Entire

Echinops grijisii

Compositae

Root

Scu tellaria indica

Labiatae

Root

Echinops latifolius

Compositae

Root

Sempervivum armenum

Crassulaceae

Leaf

Echites vucatanensis

Apocynaceae

Latex

Sempervivum arvense

Crassulaceae

Leaf

Epilobium hirsutum

Onagraceae

Entire

Swiet enia humilis

Meliaceae

Seed

Euphorbia ebracteolata

Euphorbiacaeae

Aerial parts

Tabebuia impetiginosa

Bignoniaceae

Stem bark and wood

Euphorbia heterophylla

Euphorbiacaea

Stem

Tabebuia rosea

Bignoniaceae

Stem bark and wood

Euphorbia marginata

Euphorbiacaeae

Entire

Tabebuia serratifolia

Bignoniaceae

Stem bark and wood

Euphorbia kansui

Euphorbiacaeae

Root

Thalictrum fabri

Ranunculaceae

Root

Euphorbia prolifera

Euphorbiacaeae

Latex

Thevetia ahouia

Apocynaceae

Le af Stem

a nd

Ficus pretoiae

Moraceae

Sap

Thevetia gaumeri

Apocynaceae

Le af Stem

a nd

Hedyotis chrysotricha

Rubiaceae

Entire

Thevetia peruciana

Apocynaceae

Le af Stem

a nd

Hippophae salicifolia

Elaeagnaceae

Fruit

Uncaria tomentosa

Rubiaceae

Bark

Hypoxis nyasica

Hypoxiaceae

Rhizome

Virola bicuhyba

Myristicaceae

Seed

Hypoxis rooperii

Hypoxiaceae

Tuber

Viscum album

Loranthaceae

Leaves

Inula linariaefolia

Compositae

Flowers

Viscum calcaratum

Loranthaceae

Entire

18

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CONCLUSION Research work done up to date has shown the importance of medicinal plants in the field of different human diseases including cancer, intense efforts and multiple approaches have fructifies in form of number of anti-cancer drugs in the area but the main problem associated with these drugs is the toxicity, solubility and lack of specificity as healthy cells are also become the target, most of the modern anti-cancer drugs available are either inspired from natural product or their analogues, efforts are still required to keep the delicate balance between toxicity, bioavailability and efficacy, drugs available are not good enough to treat cancer at advance stage though may prolong the life span of person, other drawback is the cost of anti-cancer drugs which must also be taken into account for the countries like India, a lot need to be done and nature has given the direction. More clinical trials are also needed to validate the usefulness of these agents either alone or in combination with existing therapy. ACKNOWLEDGMENTS The authors are grateful to the Director CSIRCDRI, Lucknow, India for providing excellent library facilities and UGC, Government of India, New Delhi for providing financial support in the form of Emeritus fellowship to VL. REFERENCES 1. American Cancer Society. Cancer Facts and

www.ijsir.co.in

2.

3.

4.

5.

6.

7.

Figures. American Cancer Society Inc 250 Williams Street, NW, Atlanta, GA. American Cancer Society, 2012. Stewart BW, Kleihues P, editors World Cancer Report (World Health Organization, International Agency for Cancer Research), IARC Press, Lyon, France, 2003, p. 11-20. Golub TR, Slonim, DK, Tamayo P, Huard C, Gaasenbeek M, Mesirov JP, Coller H, Loh ML, Downing JR, Caligiuri MA, Bloomfield CD, Lander ES. Molecular classification of cancer: class discovery and class prediction by gene expression monitoring. Science 1999;286:531-537. Hakomori SI. Aberrant glycosylation in cancer cell membranes as focused on glycolipids: overview and perspectives', Cancer Res 1985;45:2405–2417. Ogata S, Muramatsu T, Kobata A. New structural characteristic of the large glycopeptides from transformed cells. Nature 1976;259:580–582. Altenburger R, Backhaus T, Boedeker, W, Faust M, Scholze M, Grimme LH. Predictability of the toxicity of multiple chemical mixtures to Vibrio fischeri: Mixtures composed of similarly acting chemicals. Environ Toxicol Chem 2000;19:2341–2347. Warne MSJ, Hawker DW. The number of components in a mixture determines whether synergistic and antagonistic or additive toxicity predominate-The funnel hypothesis. Ecotoxicol Environ Saf 1995;31:23–28.

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AGING IN INSECTS: AN OVERVIEW *Kalpana Singh Department of Zoology, University of Lucknow, Lucknow, Uttar Pradesh, India *Address for correspondence : Dr. Kalpana Singh, Assistant Professor, Department of Zoology, University of Lucknow, Lucknow, Uttar Pradesh, India Email ID: drkalpanasingh@gmail.com ABSTRACT Aging can be defined as a decline in rate of physiological repair, an increase in probability of death and a decline in fertility with advancing adult age. It affects virtually all demographic, behavioral and physiological parameters in an individual. Its effect on activity levels and reproductive behaviour such as mate choice are well studied in insects. Reproductive attributes such as fecundity and egg viability are affected by the age of mating pair; however effects of paternal age are less studied. Effects of maternal age on offspring life span are well established in many animal groups (Lansing effect). Many theories have been proposed to explain the causes and evolution of aging; viz. mutation accumulation hypothesis, antagonistic pleiotropy hypothesis, disposable soma theory. Lansing effect may also play an important role in evolution of aging emphasizing the importance of parental age at the time of reproduction. Keywords: Aging; Mate Choice; AternalAge; Paternal Age; Progeny Fitness INTRODUCTION Aging is a function of time over biological systems. It has fascinated the scientists the world over since it affects each and every aspects of life. It still remains a great mystery although systematic efforts have been going on since last century to understand it. It affects the life [1,2,3] attributes and physiology of organisms. All over the biological world only a small percentage of organisms survive in nature that are subjected to age. The effects of aging are much more pronounced in captive populations that live in benign condition.[4,5]Insects being a good model, a lot of base line studies have been conducted on them[6] although there are numerous studies on human beings and other mammals.[7,8,9,10] Since, life span of insects is very short so the genetics and evolution of genetics had predominantly investigated in insects.[6] Aging has been defined in many ways. As per physiological definition it is a decline of state of repair with increasing age. While actuarial definition states it as an increase in mortality rates of a population with increasing age. As per evolutionary definition it is a persistent decline in components of fitness (rates of survival and [11] reproduction) with increasing age. 20

Thus, aging can comprehensively be defined as a decline in fertility, a decline in rate of physiological repair and an increase in probability of [11] death with advancing adult age. There are numerous prolonged demographic studies that report aging in the form of an increase in probability of death and decline in fertility with [12] advancing adult age. Its rate may differ and evolve in different organisms although it is [13] recognized that aging is maladaptive. Keeping in view the universal presence of aging this article aims to review the studies on aging, aging theories, aging rates and aging effects on life attributes in insects. THEORIES OF AGING Various theories have been put forward to explain the phenomenon of aging and its causes and evolutionary significance. These theories can be summed up into two categories intrinsic [14] (programmed) and extrinsic (Stochastic). These two types of theories interact also such as in disposable soma (extrinsic) theory. There are many theories that may fall into intrinsic theory category such as mutation accumulation hypothesis and antagonistic www.ijsir.co.in


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pleiotropic hypothesis. Mutation accumulation hypothesis states that the aging is caused due to the increase in mutation rates along with the decreasing force of natural selection and this in turn leads to less probability of survival at later [3,15,16] ages. This corroborates with the studies conducted since 1940's where evolutionary biologists have argued that the age related decrease in the force of natural selection leads to evolution of aging.[17,2,3] According to antagonistic pleiotropic hypothesis a new mutation that increases fertility and fitness levels at young age at the expense of lowered fitness levels later in life (pleiotropic effect) will be selected.[2,15,16] Disposable soma theory of aging explains that aging is an environmentally driven balance between investment in reproduction and [18] maintenance of soma. It observes that (i) somatic maintenance has a cost, (ii) maintenance of the soma more than the natural expectation of life is disadvantageous, and (iii) maximum deaths in natural populations is due to extrinsic mortality. This is a physiological ecology based life history optimization theory that somewhere converges with the antagonistic pleiotropy theory of aging.[19,18] According to Heininger(2012)[14] aging is a deprivation syndrome driven by a germ soma conflict. This helps to explain the multiple life history trade-offs occurring in organisms. The studies conducted on Drosophila melanogaster have substantiated the mutation and antagonistic pleiotropy theories of aging.[20,15,21,22] Results of experiments conducted on D. melan[23,24,25] ogaster about age specific genetic variance [26] & inbreeding depression have corroborated the importance of mutation accumulation in aging. However there are studies on artificial selection experiments that enforce the importance of pleiotropy. Gerontologists have shown great [21, 27] interest in antagonistic pleiotropic studies. EFFECTS OF AGE ON LIFE TTRIBUTES On Activity Levels Predator's age have been found to influence rate of predation in ladybird beetle, C. transversalis and C. sexmaculata. Rate of assimilation and speed of locomotion were also found to decline with increase in age that indicates senescence.[28] Almost all demographic, behavioral and physiological parameters are known to qualiwww.ijsir.co.in

[12,29]

tatively deteriorate with the increase in age. Reproductive senescence in terms of decrease in fecundity and exhaustion of reserves in adults has been demonstrated in hymenopteran parasitoids, [30] [31,32,33] [34] lepi dopterans & ladybirds. On Mate Choice There are many studies that investigate the role of age in the choice of mates in insects. These studies have come out with three various models that explain the behavior of female exerting the age based choice of mates. Few studies suggest that females tend to choose old males as mates and this formulates the good genes model or indicator mechanism.[35,36,37,38]This theory explains that older males have proven their fitness by their long [29,40] survival thus should be selected. There are [41,42,43,44,45,46,47] many studies to substantiate the same. This model suggests that that individuals differ in genetic quality leading to increased survival and fecundity of higher quality individuals at all ages. However there are some contrary reports. [48,49,50,51,52] Mate choice model put forward by [53] Hansen &Price (1995) presents that females [54,55] choose younger males as mates. They suggest that a trade-off between early and late-life fitness components is likely to lead to such preference. The third model suggests that female choose middle aged mates.[56,57] On Mating Incidences There are many studies that report the effect of aging on mating incidences i.e. how many mating does a insect undergoes at different ages. Age specific mating incidences have been recorded in Adaliabipunctata to analyze the phenomenon of [58] protandry and protogyny. The males started mating after 4 days of age while female mated at the age of 2 days in Coccinellaseptempunctata. Age related decrease in willingness to mate and decrease in mating incidences were found after 40-50 days of age in both the sexes of this [59] beetle. In pale morph of Propyleadissecta few younger females have chosen the older males while older females have chosen the older males.[60] On Male Reproductive Attributes There are very few studies on insects dealing with effect of paternal (male) age on reproductive fitness of its own or that of females. Studies in ladybirds considering the assessment of paternal 21


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age effects on reproductive attributes came out with significant results. Viability of eggs laid was found to be male-age-dependent function. Up to the age of 30 days there was no decline in percent [ 60] viability in pale morph of Propyleadissecta and decline was observed after 30 days in Coccinellaseptempunctata[59] and Cheilomeness exmaculatus.[61] The effects of male age and its effects are largely ignored aspect of studies in insects. However Fox et al., (1995)[62]dealt with variation in ejaculate size with age and its effect on female fecundity. On Female Reproductive Attributes Some lepidopterans exhibit a decline in egg [63, production with increasing age of mother. 64,65,66,67,68] Decline in egg size with advancing maternal age have been reported in butterflies that [69,70,71,72] lay their eggs singly. In braconid Micro [73] plitscroceipes (Cresson), chalcid, Brachy-meris [74] inter media (Nees) and Female moth Epi[75] phyaspostvittana (Walker) showed decreasing fecundity and fertility with increasing age. In ladybeetle, C. montrouzieri fecundity was significantly affected by the age of female, as 5 to 15-day-old females laid larger number of eggs.[76]In ladybirds C. septempunctata and P. dissecta(pale morph) fecundity was affected by the advancing age of the females. Senescence was reported after 20 days in females of both the ladybirds.[60,59] In Drosophila melanogaster it was reported that the last male sperm precedence declined significantly in three strain of the species indicating the start of senescence as physiological [77] deterioration. Effect of Aging on Offspring Fitness The younger mother, on the average, had the longest lived offspring-Alexander Graham Bell (1918) . Researchers have found that in insects older mothers have shorter lived offspring in house flies,[78] fruit flies,[79] stink bugs,[81]flour beetles,[82]and mealworms.[83,84] This is referred to as the Lansing effect,after Albert Lansing's (1947,1948,1954) [ 8 5 , 8 6 , 8 7 ] renowned work on rotifers. In C. montrouzieri the female age had nonsignificant effect on development of grubs.[76] However in fruit flies it was reported that delayed 22

mating of mothers had affected the rate of recombination and non-disjunction in their [88] offspring. In Brachymeriaintermedia (Nees) [89] maternal age controls itspopulation growth. [90] Priest et al.,(2002) reported that age of mother had affected the longevity of her offspring. In the wild caught strain of D. melanogaster age of mother had affected the male progeny life expectancy. It was found that mothers which reproduced continuously throughout their life have offspring with higher life expectancy than the mothers with delayed reproduction. The results show that maternal age affects the patterns of aging of offspring. A single study in ladybirds demonstrates that the age of parental generation affects the reproductive parameters of progeny thus playing critical role in [91] determining fitness of future generations. CAUSES AND EVOLUTION [10] Kirkwood (2002) explains aging with the disposable soma theory that tells that aging is a balance between investment in reproduction and maintenance of soma which is also environmentally modulated. Whereas, Heininger (2012)[14] has explained aging as a deprivation syndrome driven by a germ soma conflict. The Lansing effect predicts that the older mother produce short lived offspring. This effectmay also have asignificant role in the evolution of aging. Natural selection may also operate on the offspring produced by parents of different ages thus influencing the evolution of aging provided the effect of parental age on offspring longevity varies among different genotypes. There are many studies that show that longevity and survival of the organisms including insects depends on their sexual activity in males and reproductive efforts in terms of mating, [92, 93,94,95,96] oviposition in females. Life history evolution for understanding the mechanism of aging has been explained by resource allocation models. This model postulates that there is a trade-off between different life history traits and reproduction is costly and often results in either lowered fecundity or survival . [1, 97, 98,99,100,101] This trade-off is well studied in Arthropoda especially in insects. [20,94,102,27,103] Increased reproduction is costly as it may lead to www.ijsir.co.in


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reduced longevity. In female insects it is [35,102] expressed as purely phenotypic effects or as [104] additive genetical effects. It is very well [92] demonstrated in D. melanogaster. ACKNOWLEDGEMENT The author is grateful to the Head, Department of Zoology, University of Lucknow, Lucknow, Uttar Pradesh, India for providing necessary laboratory facilities. REFERENCES 1. Fisher, R. A. The Genetical Theory of Natural Selection. Oxford: Clarendon Press. (1930). 2. Williams, G.C. Pleiotropy, natural selection and the evolution of senescence. Evolution. (1957); 11: 398-411. 3. Hamilton, W.D. The molding of senescence by natural selection. Journal of Theoretical ...... 1 Biology. (1966); 12:12-45. 4. Ricklefs, R.E. Evolutionary theories of aging: confirmation of a fundamental prediction, with implications for the genetic basis and evolution of life span. The American Naturalist.(1992); 152:24-44. 5. Wachter, K.W. & Finch. C.E. Between Zeus and the Salmon. The Biodemography of Longevity. National Academy Press. (1997). 6. Arnqvist, G. & Nilsson, T. The evolution of polyandry: multiple mating & female fitness in insects. Animal Behavior.(2000); 60: 145164. 7. Finch, Caleb E.; Tanzi, Rudolph E.Genetics of Aging. Science. (1997); 278, (5337), p. 407 (1997). 8. Kirkwood, T.B.L. &Austad, S.N. Why do we age. Nature.(2000); 408: 233-238. 9. Kirkwood, T.B.L. Human senescence. BioEssays.(1996); 18:1009-1016. 10. Kirkwood, T.B.L. Evolution of ageing. Mechanisms of Ageing Development.(2002); 123:737-745. 11. Mangel, M. Complex adaptive systems, aging and longevity. Journal of Theoretical Biology.(2001); 213:559-571. 12. Finch, C.E. Longevity, Senescence and the Genome. University of Chicago, Press.(1990); pp. 922. 13. Medawar, P.B. An Unsolved Problem of Biology. H. K. Lewis, London. (1952). www.ijsir.co.in

14. Heininger K. The Germ-soma Conflict Theory of Aging and Death: Obituary to the "Evolutionary Theories of Aging". Webmed Central AGING (2012); 3(4):WMC003275 doi: 10.9754/ journal.wmc.2012.003275 15. Partridge, L. & Barton, N.H. Optimality, mutation and the evolution of aging. Nature.(1993); 362:305-311. 16. Pletcher, S.D. and Curtsinger, J.W. Mortality plateaus and the evolution of senescence: why are old-age mortality rates so low? Evolution. (1998); 52: 454-464. 17. Medawar, P.B. Old age and natural death. Mod. Q. (1946); 2:30-49. 18. Kirkwood T. B. L. and Rose, M. R. Evolution of Senescence: Late Survival Sacrificed for Reproduction. In, The Evolution of Reproductive Strategies (1991); pp. 15-24 19. Kirkwood, T. B. L. Evolution of ageing. Nature, Lond. (1977); 270, 301-304. 20. Rose, M. Laboratory evolution of postponed senescence in Drosophila melanogaster. Evolution.(1984); 38:1004-1010. 21. Zwaan, B., Bijlsma, R. & Hoekstra, R.F. Direct selection on life span in Drosophila melanogaster. Evolution. (1995); 49: 649659. 22. Charlesworth, B. & Hughes, K.A. Age specific inbreeding depression and components of genetic variance in relation to the evolution of senescence. Proceedings National Academy of Sciences, USA. (1996); 93:6140-6145. 23. Hughes, K.A. &Charlesworth, B. A genetic analysis of senescence in Drosophila. Nature.(1994); 367:64-6611. 24. Promislow, D.E., Tatar, M., Khazaeli, A.A. &Curtsinger, J.W. Age-specific patterns of genetic variance in Drosophila melanogaster. I. Mortality. Genetics. (1996); 143: 839-848. 25. Tatar, M., Promislow, D.E.L., Khazaeli, A.A. &Curtsinger, J.W. Age-specific patterns of genetic variance in Drosophila melanogaster. II. Fecundity and its genetic covariance with age-specific mortality. Genetics. (1996); 143: 849-858. 26. Charlesworth, B. & Hughes, K.A. Age specific inbreeding depression and components of genetic variance in relation to 23


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male quantitative traits in lizards- Why is it so rare? Behavioral Ecology and Sociobiology. (1995); 36:179-184. 53. Hansen, T.F. and Price, D.K. Good genes and old age: do old mates provide superior genes? Journal of Evolutionary Biology.(1995); 8:769-778. 54. Alatalo, R., Gustafsson, L. & Lundberg, A. Do females prefer older males in polygynous bird species? The American Naturalist. (1986); 127:241-245. 55. Price, D.K. & Hansen, T.F. How does offspring quality change with age in male Drosophila melanogaster? Behavioral Genetics. (1998); 28: 395-402. 56. Beck, C.W. & Powell, L.A. Evolution of female mate choice based on male age: Are older males better mates? Evolutionary ...... 1 Ecology Research.(2000); 2:107-118. 57. Jones, T.M., Balmford, A. &Quinnell, R.J. Adaptive female choice for middle-aged mates in a lekkingsandfly. Proceedings of the Royal Society of London, Series B.(2000); 267: 681-686. 58. Hemptinne, J.L., Dixon, A.F.G. & Adam, B. Do males and females of the two-spot ladybird, Adaliabipunctata (L.) differ in when they mature sexually? Journal of Insect Behavior.(2001); 14(3): 411-419. 59. Srivastava, S. and Omkar. Age specific mating and reproductive senescence in seven spotted ladybird, Coccinellaseptempunctata. Journal of Applied Entomology. (2004); 128 (6):452-458 60. Pervez, A., Omkar and Richmond, A.S. The influence of age on reproductive performance of a predatory ladybird beetle, Propyleadissecta. Journal of Insect Science. USA. (2004); 4 (22): 1-8. 61. Omkar, Singh S. K. & Singh K. Effect of age on reproductive attributes of an aphidophagous ladybird, Cheilomenessexmaculata. Insect Science. (2006); 13( 4): 301–308, August 2006 62. Fox, C.W., Hickman, D.L., Raleigh, E.L., &Mousseau, T.A. Paternal investment in a seed beetle (Coleoptera: Bruchidae): influence of male size, age, and mating www.ijsir.co.in

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APPLICATION OF CARBON NANOTUBE AS A GAS SENSOR *Roshni Yadav and C.K.Dixit Department of Physics, Faculty of Science & Technology, Dr. Shakuntala Misra National Rehabilitation University, Mohaan Road, Lucknow, Uttar Pradesh, India *Address for correspondence: Roshni Yadav, Research Scholar, Department of Physics, Faculty of Science & Technology, Dr.Shakuntala Misra National Rehabilitation University, Mohaan Road, Lucknow, Uttar Pradesh, India Email ID: ry_phyphd2016@dsmnru.ac.in ABSTRACT Gas Sensor is the most growing application of the materials and also it has become the most prominent field for the researchers because of its sensitivity, fast response and stability. With the advancement of the Nano technology, it has created a new changed path for high sensitiveness at low cost and room temperature, portable sensitivity with low power consumption. Due to the hollow structure and high surface to volume ratio of the nano particles, it is suitable for the adsorption of gas molecules. With the emergence of Carbon Nano tube (CNT) the advancement of the gas sensors has exploited the CNT's peculiar structural configurations, morphology and its properties. Various changes are visible in the CNT's on the exposure of the gases. In this paper Carbon Nano tube in a gas sensing technology and its mechanisms with both experimental as well as theoretical simulations are reviewed involving the challenges in the research process. Keywords: Carbon nanotube;Nanotechnology;Sensor;Morphology INTRODUCTION Gas sensors are the most interested topic because of its extensive application in almost every sphere of the world and in our daily lives as in various industries, biomedicine, environmental or refrigeration monitoring. Gas sensors of good effectiveness possess the sensitivity, reliability, responsive at room temperature and lastly cost effective. Different mechanisms occur during the gas sensing phenomenon and thus we can classify them on this basis. Considering the carbon nanotube as the gas sensing material it has unique properties because of its large surface area, hollow center and most importantly nanoscale measurement and thus further they are capable to undergo extreme variation in electrical resistance when exposed to halogens, alkali and other different gases at room temperature. [1] So, experimentally and theoretically we can start to arise with the fact that the carbon nanotube has the prospects of developing into a good chemical sensor. The cylindrical allotropes of carbon are linked together to form the nanotube structures. Carbon nanotube is gradually becoming more apparent in the sensor industry. The main ability 28

of these carbon nanotubes is to conduct electricity and communicate this energy wave across its structure resulting in advancement into a highly sensitive sensor component. Carbon Nanotubes were illustrated and discovered by S. Injima, Japan, in 1991. An astonishing sensation involved in nanotubes is their dependence of the properties on their shape. CNT have an elongated cylindrical structure where its diameter varies from 1 to several dozensof nanometer and length varies from several microns containing one or more hexagonal graphite planes rolled in tubes .[2] Nano-ranged Carbon nanotube based gas sensors of the field effect transistor type possess the high selectivity at room temperature due to the sudden change of electrical conductivity upon the adsorption of various gases.[3,4]Carbon nanotube is generally categorized as Single Wall Carbon Nanotube (SWNT) [5] and Multi wall Carbon Nanotube (MWNT) [6] with two distinct structural familiarities. SWNT are composed of a single graphite sheet rolled seamlessly whereas, MWNT are concentric and closed graphite tubles. www.ijsir.co.in


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CARBON NANOTUBE AS A SENSING MATERIAL Nanotube is a surface structure whose entire weight is concentrated on the surface of its layers and hence this feature of CNT's predetermines their electrochemical and adsorption properties due to the large unit surface of tubulenes.[2] Designing of the sensors on the basis of nanotubes is possible due to the high adsorption capacity and sensitivity of the CNT properties where the molecules are adsorbed on their surface.[7-9] Gas sensors can be categorized in other types on the basis of the CNT which are discussed as follows: a) Sorption gas sensors. b) Ionization sensors. c) Capacitance gas sensors. d) Resonance frequency shift gas sensors. Sorption Gas Sensors are one of the vastest [8] group of gas sensors and the operation principle of the sorption gas sensors is the adsorption through which an adsorbed gas molecule transfers an electron to and takes it from a nanotube which changes the electrical properties of the CNTs. Ionization sensors are another type of gas sensors with low adsorption sensing on the basis of CNT challenging for their general use [2]where in their application is inhibited by the prerequisite of using high sensitivity signal processing devices and degradation of the CNT sensitive element because of coronary discharges. Capacitance gas sensors is another form of sensors in which CNT arrays are being employed a s s e n s i t i v e e l e m e n t s . J . T. W. Ye o w [10] etal. described an array of mis-oriented nanotubes grown on a SiO2layer where the first plate of the sensor was a CNT array and the other plate was silicon. When external voltage is applied between the two plates high value electric field is generated at the CNT terminations resulting in polarization of adsorbed molecules and increase in capacity. For the Resonance frequency shift gas sensors variationin the electrical properties of the CNT during their interaction with gases is observed.[1112] Major drawback of resonance frequency shift gas sensors is the requirement of using additional equipment for inspecting the dielectric permeability and resonance frequency. FABRICATION OF CNT GAS SENSORS www.ijsir.co.in

Various different types of methods are employed for the integration of the CNTs to other gas sensor [13] structures. Li et. al. described the resistive gas sensors by casting SWCNTs on interdigitated electrodes. Fabrication of the electrodes were done by photolithography and evaporation of Ti and Au on silicon oxide. Firstly, the grown SWCNTs were purified with acid and then by air oxidation before being integrated with the IDEs resulting into the final SWCNTs having a relatively high purity up to 99.6%, and the effect of impurities on the sensor's characteristic were minimized. The purified nanotubes were then dispersed in dimethylformamide (DMF) and drop-deposited onto the electrode area.Similarly, various other methods were developed for the fabrication process. GAS ADSORPTION ON CNTS BY THE ORETICAL AND SIMULATION STUDIES The adsorption of different gas molecules on CNTs are usually calculated by first-principles calculations employing density functional theory (DFT). The binding energy, tube-molecule distance, and change transfers are calculated. Zhao et al. [14] described the adsorption of various gas molecules (NO2, O2, NH3, N2etc) on single SWNT and SWNT bundles applying the first principles method. Peng and Cho[15] described the adsorption of NO2 on to SWNTs. One binding configuration for NO2 gas molecule on the SWNT with three units as shown in fig1 shows the NO2 gas molecule of the configuration is binded with SWNT containing adsorption energy of 0.3  eV, and resulting in the molecules high diffusion kinetics on nanotubes surfaces. Electron density analysis indicates that the charge is transferred / induced from C atom to the NO2 gas molecule leading to hole doping of semiconducting nanotubes. The equilibrium tubemolecule distance, adsorption energy, and change transfer for various molecules on, and SWNTs were calculated for individual SWNT. The results indicate that the most of the reviewed molecules (except for NO2 and O2) are charge donors with small charge transfer. These gas molecules are identified to be as physisorption. O2 and NO2, indicate that they both are charge acceptors with large charge transfer and adsorption energies. 29


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Fig 1: (a) Total valence electron charge density plot. The value of charge contour is 0.0015 (el/Å3) showing the binding charge between the SWNT and the NO2 molecule. Three units are shown in this figure. Kay Hyeok. An et al while performing experimentally illustrated the recovery behaviour of the sensitivity as a function of gas exposure time and described when the gas was exposed the the annealed sample the sensitivity increased and when the supply was switched off the sensitivity gradually started decreasing. The resistivity decreased to a lower value after a long degassing time. However, this effect decreased in the next

(b) Binding energy curve for NO2 interacting with SWNT as a function of distance from NO2 to the nanotube. The solid line curve is a fitting with universal binding curve [15]. cycle and the sensitivity was also recovered after the 2 hours for the SWNT and the nanocomposite. Further, in other cycle the sensitivity was degraded and also not recovered but a small amount of NO2 remained in the sensor while fabricating the S W N T/Ppy gas sensors. Concluding with a SWNT sensor of n-type behaviour. [16]

Fig. 2: The change of sensitivity as a function of gas exposure time at an NO2 concentration of 3000ppm: (a) Annealed Sample (b) the second cycle after 24hr (c) the third cycle after 48 hr. (d) the change in sensitivity as a function of cycle no .[16] 30

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CONCLUSION Carbon Nanotube based Gas sensors have gained a major application in every aspect due to their high potential and high surface area and thus it is playing a pivotal role in the sensing applications. Experimentally and theoretically it is highly demonstrated that the CNTs are the most exciting materials for the sensing application with its different structural definitions. Single Walled Nanotube as well as Multi-Walled Nanotube due to its distinct configurations provides an exciting gas sensing performance with high selectivity and responses. With the increasing interest and the technology involving the CNT gas sensors it is becoming a promising topic of research with new complications. REFRENCES 1. Jang Y.T, Moon S.I, Ahn J.H, Lee Y.H and Ju B.K, (2004). A simple approach in fabricating chemicalsensor using laterally grown multiwalled carbon nanotubes. Sensors and Actuators B 99: 118-122. 2. Irina V. Zaporotskova, Natalia P. Boroznina, Yuri N. Parkhomenko, Lev V. Kozhitov Carbon nanotubes: Sensor properties. A review Modern Electronic Materials 2 (2016) 95–105. 3. J. Kong, N.R. Franklin, C. Zhou, M.G. Chapline, S.Peng, K.Cho , H. Dai, Science 2000, 287,622. 4. P.G. Collins, K. Bradley, M. Ishigami, A. Zettl, Science 2000, 287, 1801. 5. S.Iijima, T.Ichihashi, Nature 1993, 363, 603. 6. S.Iijima, Nature 1991, 354, 56. 7. K.F. Akhma-dishina, I.I. Bobrinetskii, I.A. K o m a r o v, A . M . M a l o v i c h k o , V. K .

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Nevolin,V.A. Petukhov, A.V. Golovin, A.O. Zalevskii, Flexible biological sensors based oncarbon nanotube films, Nanotechnol. Russ. 8 (11–12) (2013) 721–726. 8. Zhang Wei-De, Zhang Wen-Hui, Carbon nanotubes as active components for gassensors, J. Sens. 2009 (2009) 16. 9. A. Boyd, I. Dube, G. Fedorov, M. Paranjape, P. Barbara, Gas sensing mechanism ofcarbon nanotubes: from single tubes to high-density networks, Carbon 69 (2014)417–423. 10. J.T.W. Yeow, J.P.M. She, Carbon nanotu been hanced capillary condensation for acapacitive humidity sensor, Nanotechnology 17 (21) (2006) 5441–5448. 11. S. Chopra, K. McGuire, N. Gothard, A.M. Rao, A. Pham, Selective gas detectionusing a carbon nanotube sensor, Appl. Phys. Lett. 83 (11) (2003) 2280–2282. 12. V.A. Buzanovskii, Electrochemical sensors based on carbon nanotubes and theiruse in biomedical research, Bio meditsinskayakhimiya 57 (6) (2011) 12–31. 13. J. Li, Y. Lu, Q. Ye et al., “Carbon nanotubes sensors for gas and organic vapour detection,” Nano Letters, vol. 3, no. 7, pp. 929–933, 2003. 14. J. Zhao, A. Buldum, J. Han, and J. P. Lu, “Gas molecule adsorption in carbon nanotubes and nanotube bundles,” Nanotechnology, vol. 13, no. 2, pp. 195–200, 2002 15. S. Peng and K. Cho, “Chemical control of nanotube electronics,” Nanotechnology, vol. 11, no. 2, pp. 57–60, 2000. 16. Kay HyeokAn, SeungYolJeong, Ha Ryong Hwang, Young Hee Lee, Adv. Mater. 2004,16, No.12, june 17.

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AN OVERVIEW OF ANDROGRAPHIS PANICULATA (BURM. F.) NEES *Vijai Lakshmi, Santosh Kumar Agarwal and Abbas Ali Mahdi Department of Biochemistry, King George's Medical University, Lucknow, Uttar Pradesh, India *Address for Correspondence: Dr. Vijai Lakshmi, Emeritus Scientist, Department of Biochemistry, King George's Medical University, Lucknow Uttar Pradesh, India Email ID:vijlakshmius@yahoo.com ABSTRACT A lot of literature reviews about Andrographis paniculata has been published previously. Researchers are critically involved in the research to extract out the potential medicinal value which is present in this plant. It has a broad pharmacological value. The plant has many potential compounds but the major activities are because of the presence of few bioactive compound andrographolide and its different metabolites. The extremely bitter taste of the plant is due the presence of this compound. From the review of the literature on this plant we found that this plant has antioxidant, hepatoprotective, antimicrobial, anticancer, antivenom, anti HIV, antimalarial, antipyretic, antifertility, antidiarrhoeal, antidiabetic, antihiperlipidemic activities. Keywords: Andrographis paniculata; pharmacological activities; bioactive molecules. INTRODUCTION Nature has been a source of medicinal agents for thousands of years and since the beginning of mankind. Medicinal plant is an integral part of human life to combat the sufferings from the dawn of civilization. It is estimated that more than 80,000 of total plant species have been identified [1] and used as medicinal plants around the world. Over the past twenty years, interest in medicinal plants has grown enormously from the use of herbal products as natural cosmetics and for selfmedication by the general public to the scientific investigations of plants for their biological effects [2] in human beings. Therefore, people are encouraging indigenous production and processing of these medicinal plants to use in different cultures and religion for the treatment of

various diseases.[3]The demand for plant based medicines, health products, pharmaceuticals, food supplement, cosmetics etc are increasing in both developing and developed countries, due to the growing recognition that the natural products are non-toxic, have less side effects and easily [4] available at affordable prices .Now a days, there is a revival of interest with herbal-based medicine due to the increasing realization of the health hazards associated with the indiscriminate use of modern medicine and the herbal drug industries is now very fast growing sector in the international [5] market .There is great demand for herbal medicine in the developed as well as developing countries like India, because of their wide biological activities, higher safety of margin than

Andrographis paniculata leaves 32

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the synthetic drugs and lesser costs [ 6 , 7 ] Andrographis paniculata (Burm. f.) Nees (Acanthaceae) is a plant that has been effectively used in traditional Asian medicines for centuries. It's perceived “blood purifying” property results in its use in diseases where blood “abnormalities” are considered causes of disease, such as skin eruptions, boils, scabies, and chronic undetermined fevers. The aerial part of the plant, used medicinally, contains a large number of chemical constituents, mainly lactones, diterpenoids, diterpene glycosides, flavonoids, and flavonoid glycosides. Controlled clinical trials report its safe and effective use for reducing symptoms of uncomplicated upper respiratory tract infections. Since many of the disease conditions commonly treated with Andrographis paniculata in traditional medical systems are considered self-limiting, its purported benefits need critical evaluation [ 8 ] .Andrographis paniculata grows widely in many Asian countries, such as China, India, Thailand and Sri Lanka and has a long history of therapeutic usage in Indian and Oriental medicine. The herb is official in Indian Pharmacopoeia as a predominant constituent of at least 26 Ayurvedic formulations used to treat liver disorders. It is one of the herbs, which can be used to treat neoplasm as mentioned in ancient Ayurvedic literature. A. paniculata is reported as a cold property herb in

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Traditional Chinese medicine (TCM) and is used to get rid of body heat and to expel toxins. ETHNOBOTANICAL USES Ethnobotanically, the leaves and roots of A.panicuata have been used since centuries in Asia and Europe to cure the wide spectrum of health ailments. However, the whole plant is also used for certain limited purposes. Due to its “cold property” activity, it is recommended to be used to get rid of the body heat in fevers and to dispel toxins from the body. The plants are also recommended for the use in cases of leprosy, gonorrhea, scabies, boils, skin eruptions, and chronic and seasonal fever for its high “blood [7] purifying” properties .The overall traditional uses of AP in different traditional medicinal systems (TMS) or countries are pointed out in Table 3. In addition, it is also widely used for medicinal purposes by the traditional practitioners, tribes, or community as a folklore remedies in different countries [8]. Few chemical compounds[9] isolated and chara-cterized from the plant are as follows. PHARMACOLOGICAL ACTIVITY Research studies conducted in past decades have confirmed that Andrographis, if properly administered, has a surprisingly broad range of pharmacological effects. Some of them are extremely beneficial as follows.

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Hepatoprotective activity Only few studies on the crude extracts of A.paniculata on liver function are available. Administration of the extract to normal adult rats in single and multiple doses for seven and 15 consecutive days did not significantly affect serum transaminases [8]. A comparative study on the effect of leaf extract or andrographolide on carbontetrachloride (CCl4)-induced hepatic microsomal lipid peroxidation revealed a protective effect of a single oral dose of the extract and of andro-grapholide. However, high concentration CCl4-induced microsomal lipid peroxidation in vitro was completely protected by the extract but not by andrographolide, indicating that the hepatoprotective effect is not solely due to [9] the presence of andrographolide . Immunostimulatory activity Intragastric administration of an ethanol extract of the aerialparts (25mg/kg body weight) or purified andrographolides (1mg/kg body weight) to mice stimulated antibody production and the delayed-type hypersensitivity response to sheep red blood cells [10] . The extract also stimulated a non-specific immune response in mice, measured by macrophage migration index, phagocytosis of [14C] leucine-labelled E.coli, and proliferation of splenic lymphocytes [11]. The extract was more effective than either andrographolide or neoandrogra-pholide alone, suggesting that other constituents may be [12] involved in the immunostimulant response . Antidiabetic activity Antidiabetic property of A. paniculata was confirmed by Borhanuddin et al. and Husen et al. [13-14] in aqueous extract and by Zhang et al. in [ 1 5 ] ethanolic extract . Along with antihyperglycaemic property, the ethanolic extract may also reduce oxidative stress in [16] diabetic rats as studied by Zhang etal. . Further, it was concluded by Yu BC et al. that the andrographolide was responsible for the antihyperglycemic activity [17] . Finally, the antidiabetic potential of A. paniculata was found to restore impaired estrous cycle in alloxan induced diabetic rats [18]. Hypotensive activity Andrographis paniculata is reported to have, by acting through β- adrenoceptors, autonomic ganglion receptor and angiotensin converting www.ijsir.co.in

[19]

enzyme (ACE) inhibitory activity .The plant possesses a remarkable capability to challenge the norepinephrine induced contractions resulting in vaso relaxation in isolated rat [20]. Anti-inflammatory activity A. paniculata can also inhibit the production of inflammatory mediators and alleviate acute hazards at its optimal dosages[21]. Shen et al. observed that the andrographolide, an active component of A. paniculata, inhibits inflammatory responses by rat Neutrophils [22]. Antibacterial activity An ethanol extract of the leaves inhibited the growth in vitro of Escherichia coli and Staphylococcus aureus. A 50% methanol extract of the leaves inhibited growth in vitro of Proteus [23] vulgaris . However, no in vitro antibacterial activity was observed when dried powder from the aerial parts was tested against E. coli, Staphylococcus aureus, Salmonellatyphi or [24] Shigella species . Antimalarial activity A 50% ethanol extract of the aerial parts inhibited the growth of Plasmodium berghei both in vitro (100 mg/ml) and in mice after intragastric administration (1 g/kg body weight)[25]. Intragastric administration of a 1-butanol, chloroform or ethanol–water extract of the aerial parts to Mastomysnatalens is inhibited the growth of P. berghei at doses of 1–2g/kg body weight. Andrographolide (5 mg/kg body weight) and neoandrographolide (2.5mg/kg body weight) were also effective when administered by gastric [26] lavage . Cardiovascular Effects Aqueous extract of A. paniculata produced a dose-dependent fall in systolic blood pressure of both spontaneously hypertensive rats(SHRs) and normotensive Wistar-Kyotorats, with a corresponding significantly decrease in plasma angiotensin converting enzyme(ACE) activity [27]. The hypotensive effect of n-butanol and aqueous fractions of the crude water extract is antagonized or attenuated by phentolamine, hexamethonium, pyrilamine, andcimetidine, but not by propranolol, atropine, or captopril [28]. Effects on Reproductive Systems A number of animal studies report an effect of Andrographis paniculata on male and female 35


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reproduction. Early reports of oral administration of powdered stem indicated an antifertility effect in male Wistar mice, but no impact on fertility in female mice. It has also been reported that administration of Andrographis paniculata resulted in abortion in pregnant rabbits. Intraperitonially injection of the decoction of aerial parts to female albino mice was reported to prevent implantation and caused abortion at different gestation periods [29]. Cytotoxic Activity Hydro-alcoholic extract of A. paniculata was examined by Singh RP et al. to indicate the chemopreventive potential of A. paniculata against chemotoxicity including carcinogenicity [30] on drug metabolizing enzymes . Anti- HIV Activity Aqueous extracts of the leaves inhibited HIV1 infection and replication in the lymphoid cell line MOLT-4[64]. A hot aqueous extract of the aerial parts reduced the percentage of HIV [31] antigen-positive H9 cells . Dehydro and rographolide inhibited HIV-1 and HIV-1 (UCD123) infection of H9 cells at1.6mg/ ml and 50mg/ml respectively and also inhibited HIV-1 infection of human lymphocytes at 50mg/ml [32]. A methanol extract of the leaves suppressed syncytia formation in co-cultures of uninfected and HIV1infected MOLT cells (median effective dose [ED50] 70mg/ml) [33]. CONCLUSION The demand of A. paniculata (AP) is greatly increased in the past few years for its overwhelming therapeutic potentials. Available data on AP also clearly expresses a broad spectrum of pharmacological properties of this plant. Due to possessing extensive pharmacological activities, the AP can be safely regarded as one of the modern catholicons. However, the investigated pharmacological activities of AP need validation through the clinical study. Though several clinical studies were successfully completed without adverse effects or fatalities, most of them only investigated upper respiratory tract infections for a variety of conditions. Verification of the efficacy of other biological activities of AP including antidiabetic, anticancer, anti-inflammatory, and 36

hepato- protective activities, on human study subjects would bring a lot of benefits for the largest population of the globe. We assume that the AP could be useful as highly applied the rapeutic agent for a variety of disorders in the near future to cure human diseases as well as some animal diseases. Pharmacological and phytochemical studies are needed to find new bioactive compounds followed by efforts towards conservation of this plant. ACKNOWLEDGEMENT A research grant from University Grant Commission, Government of India, New Delhi Office, in the form of Emeritus fellowship to VL is gratefully acknowledged. REFERENCES 1. G. Chaudhary, S. Goyal, and P. Poonia, Lawsonia inermis Linnaeus: a phytopharmacological review, International Journal of Pharmaceutical Sciences and Drug Research, vol. 2, no. 2, pp. 91-98, 2010. 2. P. Joy, J.Thomas, S.Mathew, and B. P. Skaria, Medicinal plants, Tropical Horticulture, vol.2,pp. 449–632, 1998. 3. I. H. Burkill, W. Birtwistle, F. Foxworthy, J. Scrivenor, and J.Watson, A Dictionary of the Economic Products of the MalayPeninsula, Ministry of Agriculture and Co-operatives, Kuala Lumpur, Malaysia, 1966. 4. Kalia, A.N. 2005. Text Book of Industrial Pharmacognosy. Oscar publication 5 Sharma, A., Shanker, C., Tyagi L. K., Singh, M. and Rao, Ch. V. 2008. Herbal Medicine for MarketPotential in India: An Overview. Academic Journal of Plant Sciences, 1 (2): 26-36. 6 Gadre, A.Y., Uchi, D. A., Rege N. N. and Daha, S. A.2001. Nuclear Variations in HPTLC FingerprintPatterns of Marketed Oil Formulationsof CelastrusPaniculates. Ind. J. of Pharmacology, 33: 124-45. 7. S. Akbar, Andrographis paniculata: a review of pharmacological activities and clinical effects, Alternative Medicine Review,vol. 16, no. 1, pp. 66–77, 2011. 8. M. H. Kabir, N. Hasan, M. M. Rahman et al., A survey of medicinal plants used by the Deb www.ijsir.co.in


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barma clan of the Tripura tribe of Moulvibazar district, Bangladesh, Journal of Ethnobiology and Ethnomedicine, vol. 10, no. 1, article 19, 2014. 9. Wen-Wan Chao and Bi-Fong Lin, Isolation and identification of bioactive compounds in And rographis aniculata (Chuanxinlian) Chin Med. 2010; 5: 17. 10. Puri A. Immunostimulant agents from Andrographispaniculata. Journal of Natural Products, 1993; 56:995-999. 11. Vedavathy S, Rao KN. Antipyretic activity of six indigenous medicinal plants of Tirumala Hills, Andhra Pradesh, India. Journal of Ethnopharmacology, 1991;3: 193196. 12. Madav S. Analgesic and antiulcerogenic effects of andrographolide. Indian Journal of Pharmaceutical Science, 1995; 57:121-125. 13. Borhanuddin M, Shamsuzzoha M, Hussain AH.Hypoglycaemic effects of Andrographis paniculata Nees on non-diabetic rabbits. Bangladesh Med Res Counc Bull, 1994; 20:24-6. 14. Husen R, Pihie AH, Nallappan M. Screening for antihyperglycaemic activity in several local herbs of Malaysia. J Ethnopharmacol, 2004; 95:205-8. 15. Zhang XF, Tan BK. Anti-diabetic property of ethanolic extract of Andrographis paniculata in streptozotocin diabetic rats. Acta Pharmacol Sin, 2000; 21:1157-64. 16. Zhang XF, Tan BK. Antihyperglycaemic and antioxidant properties of Andrographis paniculata in normaland diabetic rats. Clin Exp Pharmacol Physiol, 2000;27:358-63. 17. Yu BC, Hung CR, Chen WC, Cheng JT. Anti hyperglycemic effect of andrographolide in streptozotocin- induced diabetic rats. Planta Med, 2003;69:1075-9. 18. Reyes BA, Bautista ND, Tanquilut NC, Anunciado RV,Leung AB. Anti- diabetic potentials of Momordicacharantia and Andrographis paniculata and their effects on estrous cyclicity of alloxan-induced diabetic rats. J Ethnopharmacol, 2006; 105:196-200 1 9 . Ta n B K , Z h a n g C , K u r o y a n g i M . Cardiovascular activity of 14-deoxy-11 12didehydro-andrographolide in the www.ijsir.co.in

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anaesthetized rat and isolated right atria. Pharmacol Res,1998; 38:413-417. Naidu S, Asmawi M, Amirin S. Vasorelaxant effect of chloroform extract of Andrographis paniculata on in vitro rat thoracic aorta, 2007, 12. Chao WW, Kuo YH, Hsieh SL Lin BF. Inhibitory effects of ethyl acetate extract of Andrographis paniculata on NF-kB transactivation activity and LPS induced acute inflammation in mice. Evid Based Complement Alternat Med 2011; 2011:254531. Shen YC, Chen CF, Chia, WF. Andrographolide prevents oxygen radical production by human neutrophis: possible mechanisms involved in its anti-inflammatory effect. Br. J. Pharmacol, 2002; 135(2):399-406. Nakanishi K. Phytochemical survey of Malaysian plants: preliminary chemical and pharmacological screening. Chemical and Pharmaceutical Bulletin, 1965; 13:882-890. Leelarasamee A. Undetectable antibacterial activity of Andrographis paniculata (Burm) Wall. ex Nees. Journal of the Medical Association of Thailand, 1990; 73:299-304 Chander R. Antihepatotoxic activity of diterpene of Andrographis paniculata (kalmegh) Against Plasmodiumbergheiinduced hepatic damage in Mastomys natalensis. International Journal of Pharmacognosy, 1995; 33:135-138. Bhaumik A, Sharma MC. Therapeutic effect of two herbal preparations in induced hepatopathy in sheep. Journal of Research in Indian Medicine, 1993; 12:33-42. Zhang CY, Tan BK. Hypotensive activity of aqueous extract of Andrographis paniculata in rats. Clin Exp Pharmacol Physiol. 1996; 23:675-678. Zhang C Y, Tan B K . Mechanism of cardiovascular activity of Andrographis paniculata in the anaesthetized rats. J Ethnopharmacol 1997; 56:97-101. Zoha MS, Hussain AH, Choudhury SA. Antifertility effect of Andrographis paniculata in mice. Bangladesh Med Res Counc Bull. 1989;15:34-37

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Rajagopal S, Kumar RA, Deevi DS, Satyanarayana C, Rajagopalan R. Andrographolide, a potential cancertherapeutic agent isolated from Andrographis paniculata. J Exp Ther Oncol, 2003; 3:147-58. Chang RS, Yeung HW. Inhibition of growth of human immunodeficiency virus in vitro by crude extracts of Chinese medicinal herbs. Antiviral Research, 1988;9: 163175.

32. Chang RS. Dehydro and-rographolide succinic acid monoester as an inhibitor against the Human immunodeficiency virus (43225). Proceedings of the Society of Experimental biology and Medicine, 1991,197: 59-66. 33. Otake T. Screening of Indonesian plant extracts for anti human immunodeficiency virus type 1 (HIV-1) activity. Phytotherapy Research, 1995; 9:6-10.

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MOLECULAR DOCKING AND QSAR STUDIES OF ANTIPSYCHOTIC RISPERIDONE DERIVATIVES AGAINST SEROTON IN 5-HT2A RECEPTOR *

1

2

1

Kiran Bhargava , Prahlad Kishore Seth , Kamlesh Kumar Pant , Rakesh Kumar Dixit1and RajendraNath1 1 Department of Pharmacology and Therapeutics, King George's Medical University, (Erstwhile CSMMU ), Lucknow, Uttar Pradesh, India; 2Biotech Park, Lucknow , Uttar Pradesh, India. *Address for Correspondence: Kiran Bhargava, Department of Pharmacology and Therapeutics, King George's Medical University ( Erstwhile CSMMU ), Lucknow, Uttar Pradesh, India, Email ID: kbhargavaphd@gmail.com ABSTRACT Mental disorders have become highly prevalent due to ambitious lifestyle, urbanization, and stressful environment which incorporate depression, schizophrenia, bipolar disorder, obsessive-compulsive disorder, Alzheimer's disease, anxiety and so on. Among all the mental health issues, schizophrenia is the one of the exceptionally extreme, chronic debilitating problem with disturbance in thought, perception and emotion. In this work, we built 3D homology model of 5-HT2A Serotonin receptor using comparative homology modeling program MODELLER. The computed model was optimized by using molecular dynamics approaches and validatedby PROCHECK and Errat tool in order to obtain a stable model structure. After that we docked risperidone derivatives collected from literature with model structure of 5-HT2A Serotonin receptor using the program AutoDock 4.2, which resulted in energy-based descriptors such as Binding Energy, Intermolecular Energy, Internal Energy, Torsional Energy, vdW + Hbond + desolv Energy and Electrostatic Energy. Docked complex structure was analyzed in molecular dynamics simulation to validate stable interaction between ligand and receptor at the microscopic level. To do this we used CHARMM 22 force field from NAMD incorporated in visual molecular dynamics (VMD 1.9.2) and then evaluating the stability of complex structure by calculating RMSD values. After that a quantitative structure activity relationship (QSAR) model was built using energy-based descriptors as independent variable and pKi value as dependent variable of known risperidone derivatives with 5-HT2A Serotonin receptor, yielding correlation coefficient r2 of 0.7746. This result will be helpful in designing of more potent inhibitors against 5-HT2A Serotonin receptor prior to their synthesis. Keywords: Schizophrenia; Homology modeling; Risperidone derivatives; 5-HT2A Serotonin Receptor; Antipsychotic agents. INTRODUCTION Schizophrenia is described by positive and negative symptoms that can impact a patient's thoughts, perceptions, speech, affect, and behaviors, affecting more than 21 million people worldwide (WHO, 2015). Schizophrenia is likewise characterized by disorganized idea, which is manifested in speech and behavior. Schizophrenia etiology indicates that many factors are involved, namely genetic factors, (Levy et al., 2010; Alaerts and Del-Favero, 2009) alterations in chemical transmission (dopamine, serotonin etc.), (Lipska et al., 1993; 2004) obstetrical complications (Sorensen et al., 2004; Ho and Magnotta, 2010) and viral Infections www.ijsir.co.in

(Brown and Derkits, 2010). There is no satisfactory remedy available for prevention of the schizophrenia. Currently available marketed drugs like clozapine, chlorpromazine, risperi done, halo-peridol and olanzapine have nanomolar affinities for serotonin 5-HT 2 A and dopamine D2 receptors (Arnt and Skarsfeldt, 1998) yet have some adverse effects such as dizziness, neuroleptic malignant syndrome, diabetes, sexual dysfunction, agitation, sedation and weight gain. To treat positive as well as negative symptoms of Schizophrenia atypical antipsychotics drugs focused more on 5-HT2A receptor instead of D2 dopamine to avoid side 39


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effects called extra pyramidal symptoms (EPS). Neurotransmitter serotonin (5-hydroxy-tryptamine, 5-HT) an ancient neurotransmitter, involved in several neurophysiological and behavioral functions, acts by interacting with multiple receptors (5-HT1-5-HT7) (Anbazhagan et al., 2010). Alterations in serotonergic signalling have also been implicated in various psychiatric disorders (Anbazhagan et al., 2010). Risperidone is a second-generation extremely potent anti-psychotic agent used to treat schizophrenia with good tolerance in patients. In a large population of elderly patients the use of risperidone is associated with a lower risk of EPS compared to first generation antipsychotics drugs (Bishop and Pavuluri, 2008; Vasilyeva et al., 2013). This drug decreases the negative symptoms by acting on the serotonergic and noradrenergic receptors, while their effects on the dopaminergic pathway (Avram et al., 2011) with lower side effects reduce the positive symptoms. In this work, we had made a homology model for 5-HT2A Serotonin receptor of Homo sapiens. Risperidone derivatives were docked with computed model of 5-HT2A Serotonin receptor. Molecular dynamics (MD) simulation studies were performed on inhibitor – protein complex and after that, we have built QSAR model using energy-based descriptors as independent variable and pKi value as dependent variable of known risperidone derivatives with 5-HT2A Serotonin receptor, using Multiple Linear Regression. MATERIALS AND METHODS Protein preparation Amino acid sequence of 5-HT2A Serotonin receptor (ID: P28223) in Homo sapiens was retrieved from Uniprot database (The UniProt Consortium, 2015). Template Searching The primary amino-acid sequence was used to search for a suitable template, which was carried out by a homology search via Basic Local Alignment Search Tool (Altschul et al., 1997) against the Protein Data Bank (PDB) to generate a 3D coordinate structure. The homology search showed the crystal structure of Chimeric protein of 5-ht2b-bril in complex with Ergotamine (PDB Id: 4IB4) was found to be the best hit based on query coverage, identity, E-value, and high 40

similarity with the “A” chain, so was therefore considered as the template for homology modeling. Sequence alignment The sequence alignment of target and template was generated using the align2D module in Modeller software (Sali and Blundell, 1993). Default parameters were applied and the aligned sequences were inspected and adjusted manually to minimize the number of gaps and insertions. Homology modeling and structure refinement Homology model of the target protein was constructed using a restrained-based approach in MODELLER using a model-single module (Sali and Blundell, 1993). We built five 3D structures; among those, the best ones were judged by low discrete optimized protein energy (DOPE) and Modeller objective function. The constructed model was subjected to constraint energy minimization with a harmonic constraint of 200 kJ/mol/Å, applied for all protein atoms, using the steepest descent and conjugate gradient technique to eliminate bad contacts between protein atoms. Computations were done in vacuo with the GROMOS96 43B1 parameters set, without reaction field. An energy computation was done with the GROMOS96 implementation of SWISS- pdb Viewer (http://iqc.ethz.ch/gromos) (Guex and Peitsch, 1997). The quality of model was checked with the help of PROCHECK (Laskowski et al., 1993) and Errat (Bowie et al., 1991) tools. Inhibitors dataset Fifteen experimentally known risperidone derivatives were obtained from the literature (Avram et al., 2011). The 3D structure of known risperidone and their 15 derivatives were built using PubChem Sketcher v2.4 (https://pubchem. ncbi.nlm.nih.gov/edit2/index.html?cnt=0). All the ligands were subjected to energy minimization using the HyperChem software (HyperChem Release 7.5). Molecular docking Docking of risperidone derivatives screened from literature (Avram et al., 2011) against 5HT2A serotonin receptor structure were done using molecular docking program AutoDock 4.2 (Morris et al., 2009). Gasteiger charges are added to the ligand and maximum 6 numbers of active www.ijsir.co.in


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torsions are given to the lead compounds using AutoDock tool (http://autodock.scripps.edu /resources/adt). Kollman charges and the solvation term were added to the protein structure. The Lamarckian genetic algorithm implemented in Autodock was used for docking. Molecular dynamics simulations Molecular dynamics simulations were done using the NAMD (NAnoscale Molecular Dynamics program; v2.7) graphical interface module (Phillips et al., 2005) incorporated visual molecular dynamics (VMD 1.9.2) (Humphrey et al, 1996). The protein-ligand complex was immersed in the center of a 50 Å box of water molecules where all water molecule atoms (H-OH) were closer than 1.5 Å and a CHARMM (Chemistry at H A Rvard Macromolecular Mechanics) 22 parameter file for proteins and lipids; phi and psi cross-term map correction were used in the force field for complexes. A protein structure file (psf) stores structural information of the protein, such as various types of bonding interactions. The psf was created from the initial pdb and topology files using psfgen package of VMD. After running psfgen, two new files were generated protein pdb and protein psf and by accessing PSF and PDB files; NAMD generated

the trajectory DCD file. After the simulations, the results were analyzed in VMD by calculating the Root mean square deviation (RMSD) of the complex. 2D QSAR Risperidone and their 15 antagonists of 5-HT2A serotonin membrane receptor were used for 2D QSAR studies. Using MLR, the QSAR model was developed with six types of energybased independent variables such as Binding Energy (BE), Intermolecular Energy (IME), Internal Energy (IE), Torsional Energy (TorE), vdW + Hbond + desolv Energy (VdwE) and electrostatic energy (EE) and one dependent variable activity pKi in uM with the help of different crossvalidation procedures values. RESULTS AND DISCUSSION The sequence alignment of the query and template was shown in fig.1. The query sequence was made up of 471 residues; however, the structure of template was containing 430 residues. Using manual editing query was modeled from residue number 6 to 359 and alignment has 62% sequence identity. The result of alignment was employed to build new homology model.

Figure 1: The sequence alignment of the query protein and the template protein using align2Dscript of modeller software. Target and template have 62% sequence identity. www.ijsir.co.in

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After the optimization and energy minimization process, the best model was selected among five 3D models generated for 5-HT2A serotonin protein based on Modeller objective function and DOPE score, which are 2109.74561 kcal/mol and 45325.50391 kcal/mol, respectively. Ramachandran plot was drawn through PROCHECK (Laskowski et al., 1993) program validated the model with 87.7% of total residues in most favoured regions, 9.0% residues in additional allowed regions, 2.2% in the generously allowed regions and 1.1% in the disallowed regions. E R R AT (http://nihserver. mbi.ucla.edu, http://www.doe-mbi.ucla.edu/services/errat.

html) is a protein structure verification algorithm that is especially well-suited for evaluating the progress of model building and refinement. The program works by analyzing the statistics of nonbonded inter-actions between different atom types. A single output plot was produced by errat program that gave the value of the error function vs. position of a 9-residue sliding window. By comparison with statistics from highly refined structures, the error values have been calibrated to give confidence limits (Bowie et al., 1991). This was extremely useful in making decisions about reliability. After the errat the overall quality factor was 81.163 which have been shown in the fig. 2.

Figure 2: Errat plot for 5-HT2A serotonin receptor structure. Error values for residues as predicted by ERRAT for 5-HT2A serotonin receptor. Y-axis presents the error value and X-axis presents the amino acid sequences of 5-HT2A serotonin receptor. An error value exceeding 99% confidence level indicates poorly modeled regions. The overall quality factor assigned to 5-HT2A serotonin receptor is 81.163. Based on R1, R2, R3 and R4 groups at different positions, risperidone derivatives of 5-HT 2A 42

serotonin receptor were retrieved from literature (Avram et al., 2011) and were shown in table 1. www.ijsir.co.in


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Risperidone derivatives

Sl. No.

Molecule Name

1 2 3 4 5 6

Ris RisA RisB RisC RisD RisE

7

RisF

8

RisG

9 10 11 12 13 14 15 16

RisH RisI RisJ RisK RisL RisM RisN RisO

R1 CH3 C2H5 (C H3)2CH CH3 (C H3)2CH C6H13 H3 C-NH2 CH 2N(CH3)2 OH C4H7 C4H7 CH 3 C4H7 C4H7 C4H7 C4H7

R2 H H H (CH3)2 H H H H H H H H H H H CH3

R3 H H H H OH H

R4 F F F F F F

H H

F

H H

F F F F OH Cl COOH F

NH 2 C6 H 5 H H H H

F

Table 1: Risperidone derivatives of 5-HT2A serotonin receptor based on different R1, R2,R3 and R4 groups. In docking studies of risperidone derivatives with 5-HT2A serotonin receptor, best autodock score was used as criteria to interpret the best conformation among the 30 conformations,

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generated by AutoDock4.2 program. The docking results of the risperidone derivatives with 5-HT2A serotonin receptor were shown in table 2.

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Sl. No.

Molecule Name

Experimental pKi 9.76

Predicted pKi

BE

IME

IE

TorE

VdwE

EE

9.93

-10.54

-11.73

-0.91

1.19

-10 .78

-0.96

1

Ris

2

Ris1

8.98

9.36

-9.2

-10.69

-1.29

1.49

-10 .32

-0.38

3

Ris2

8.44

8.89

-10.25

-11.44

-1.07

1.19

-10 .84

-0.6

4

Ris3

7.06

7.00

-9.64

-12.32

-1.39

2.68

-11 .85

-0.47

5

Ris4

8.84

9.29

-10.47

-12.26

-1.13

1.79

-10 .01

-2.25

6

Ris5

8.96

8.95

-9.26

-10.76

-1.57

1.49

-9.92

-0.84

7

Ris6

8.24

8.21

-9.46

-11.25

-1.85

1.79

-10 .21

-1.04

8

Ris7

8.12

7.66

-9.66

-11.75

-2.09

2.09

-10 .63

-1.12

9

Ris8

8.84

7.78

-10.54

-12.03

-1.68

1.49

-11 .66

-0.37

10

Ris9

6.36

6.89

-8.29

-10.67

-1.82

2.39

-10 .71

0.04

11

Ris10

6.36

7.30

-9.93

-11.72

-1.93

1.79

-11 .57

-0.15

12

Ris11

9.08

8.90

-9.93

-11.72

-0.9

1.79

-10.48

-1.24

13

Ris12

9.16

8.65

-9.23

-10.72

-1.2

1.49

-10.34

-0.38

14

Ris13

9.28

8.73

-8.55

-10.63

-1.3

2.09

-10.12

-0.52

15

Ris14

9.44

9.39

-10.7

-11.89

-0.51

1.19

-10.96

-0.93

16

Ris15

9.06

9.02

-8.21

-9.7

-1.14

1.49

-9.39

-0.31

BE= Binding Energy; IME: Intermolecular Energy; IE= Internal Energy; TorE= Torsional; Energy; VdwE= vdW + Hbond + desolv Energy; EE= Electrostatic energy. Table 2: Docking results of Risperidone and their derivatives with 5-HT2Aserotonin receptor-structure with activity (pKi= - logKi). Thus from the Complex scoring and binding conformation points. ability it's deciphered that these compounds are 2D QSAR promising inhibitors for 5-HT 2A serotonin A QSAR based model has correlation coefficient (r2) of receptor. 0.7746 was obtained from risperidone and their 15 derivatives is shown in equation 1. Protein-ligand molecular dynamics Predicted pKi = 14.4942 + 25.0236 (BE) + 51.5317 simulation MD simulation is a well-known theoretical (IME) + 0.7563 (IE) -25.8375 (TorE) technique and is mainly used for evaluating the -76.1808 (VdwE) - 76.9376 (EE)……………...(1) stability of any predicted model. Therefore, the A graphical representation between experimental pKivs constructed 3D model of protein-ligand Predicted pKi is shown in Fig.3. complexes were processed for MD simulation for ps timescale with Langevin dynamics to control the kinetic energy, temperature, and/or pressure of the system. The RMSD values of complexes contain alpha carbon atoms, and all atoms were calculated by taking structure with reference 44

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Figure 3: Relationship between experimental (x-axis) and predicted (y-axis) pKi values with an r2 value 0.7746 is shown in a QSAR model developed using multiple linear regression analysis. Previously, similar study was done on D2 dopamine receptor protein with risperidone and their analogs (Bhargava et al., 2014). To assess the predictive performance of QSAR models, different crossvalidation procedures were adopted. First, in leaveone-out strategy (LOOCV), one molecule was removed from the dataset as a test compound and the remaining 15 molecules were used to build the model. This process was repeated 16 times with each inhibitor as a test molecule. CONCLUSION The built 3D structure model of 5-HT2A serotonin receptor is reliable for the binding of inhibitors. And developed QSAR model using pKi value of known risperidone derivatives with 5-HT 2A serotonin receptor as dependent variable and six energy based descriptorsindependent variable had correlation coefficient r2 value 0.7746. CONFLICT OF INTEREST The authors have no conflict of interest regarding the publication of this paper. ACKNOWLEDGEMENT For this work, the authors are grateful to the Bioinformatics Division of Biotech Park, Lucknow, Uttar Pradesh, India for providing computational facilities. The authors are thankful www.ijsir.co.in

to the Department of Pharmacology and Therapeutics, KGMU, Lucknow, Uttar Pradesh, India for providing necessary facilities for research work. This study is financially supported by the Ragiv Gandhi National Fellowship of University Grants Commission. REFERENCES 1. Alaerts M., Del-Favero J. Searching genetic risk factors for schizophrenia and bipolar disorder: learn from the past and back to the future. Hum Mutat. 2009; 30(8):1139-52. 2. Altschul S.F., Madden T.L., Schäffer A.A., Zhang J., Zhang Z., Miller W., Lipman D.J. Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res. 1997; 25(17): 3389-402. 3. Anbazhagan P., Purushottam M., Kumar H.B., Mukherjee O., Jain S., Sowdhamini R. Phylogenetic analysis and selection pressures of 5-HT receptors in human and non-human primates: receptor of an ancient neurotransmitter. J BiomolStructDyn. 2010; 27(5):581- 98. 4. Arnt J., Skarsfeldt T. Do novel antipsychotics have similar pharmacological characteristics? A review of the evidence. Neuropsychopharmacology 1998; 18(2):63-101 5. Avram S., Duda-Seiman D., Borcan F. Wolschann 45


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P. QSAR–CoMSIA applied to antipsychotic drugs with their dopamine D2 and serotonine 5HT2A membrane receptors. J. Serb. Chem. Soc 2011; 76: 263–281. 6. Bhargava K., Nath R., Seth P.K., Pant K.K., Dixit R.K. Molecular Docking studies of D2 Dopamine receptor with Risperi done derivatives. Bio information 2014; 10(1): 008-012. 7. Bishop J.R., Pavuluri M.N. Review of risperidone for the treatment of pediatric and adolescent bipolar disorder and schizophrenia. Neuropsychiatr Dis Treat. 2008; 4(1):55-68. 8. Bowie J.U., Lüthy R., Eisenberg D.A. method to identify protein sequences that fold into a known three-dimensional structure. Science 1991; 253(5016):164-70. 9. Brown A.S., Derkits E.J. Prenatal infection and schizophrenia: a review of epidemiologic and translational studies. Am J Psychiatry. 2010; 167(3):261-80. 10. Guex N., Peitsch M.C. SWISS-MODEL and the S w i s s - P d b Vi e w e r : a n e n v i r o n m e n t f o r comparative protein modeling. Electro-phoresis 1997; 18(15):2714-23. 11. Ho B.C., Magnotta V. Hippocampal volume deficits and shape deformities in young biological relatives of schizophrenia pro-bands. Neuroimage 2010; 49(4):3385-93. 12. Humphrey W., Dalke A., Schulten K. VMD: visual molecular dynamics. J Mol Graph. 1996; 14(1):33-8, 27-8. 13. Hyper Chem (TM) Release 7.5, Hypercube, Inc., 1115 NW 4th Street, Gainesville, Florida 32601, USA. 14. Laskowski R.A., MacArthur M.W., Moss D.S., Thornton J.M. PROCHECK –a program to check the stereochemical quality of protein structures. J App Cryst. 1993; 26:283–91. 15. Levy D.L., Coleman M.J., Sung H., Ji F., Matthysse S., Mendell N.R., Titone D. The Genetic Basis of Thought Disorder and Language and Communication Disturbances in Schizophrenia. J Neurolinguistics. 2010; 23(3): 176. 16. Lipska B.K. Using animal models to test a neurodevelopmental hypothesis of schizo-phrenia. J Psychiatry Neurosci. 2004; 29(4): 282-6. 17. Lipska B.K., JaskiwG.E.,Weinberger D.R. Postpubertal emergence of hyperrespon-siveness to stress and to amphetamine after neonatal 46

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MOLECULAR DOCKING AND ADME/TOX STUDY OF NIC LOSAMIDE DERIVATIVES AGAINST NS3 HELICASE OF JEV Anjali Singh, Ajay Kumar, Vivek Srivastava Department of Biotechnology, Rama University, Kanpur, Uttar Pradesh, India * Address for Correspondence: Vivek Srivastava, Department of Biotechnology, Rama University, Kanpur, Uttar Pradesh, India Email ID : viveksrivastavabio@gmail.com ABSTRACT Japanese encephalitis virus (JEV) can cause severe central nervous disease with a high mortality rate. It is dire to recognize successful and cheap antiviral medications for JEV treatment. The protease activity of NS3 is necessary for viral replication and its prohibition could be considered as a strategy for treatment of JEV infection. We reported previously that Niclosamide had lowest binding affinity at catalytic site region of the NS3 helicase in our previous work. In this work, Niclosamide similar compounds were retrieved from PubChem database and a structure-based virtual screening against NS3 helicase was carried out by AutoDock4.2. We found three potent drug-like compounds CID44240996, CID44565834 and CID88834438 among them having binding energy of -9.22, -9.27 and -9.05 kcal/mol with NS3 helicase, respectively. The docked complex structures were optimized by molecular dynamics simulation for in ps with the CHARMM-22 force field using NAMD incorporated in VMD and then evaluating the stability of complex structures by calculating RMSD. Further, in silico ADME/Tox of best predicted derivatives of NS3 helicase were evaluated. Compounds showed satisfactory results for oral administration and had HIA in the range of well absorbed compounds. PCaCO2 of these compounds were in moderate range. The cell permeability in MDCK of compounds was low varying from -4.47326nm/s to 2.80936 nm/s. Skin permeability showed negative values. Derivatives bind strongly to plasma proteins and blood-brain barrier value had less than 1. The Ames test showed compounds were mutagen and carcinogenicity in mouse and rat showed negative value except compound CID88834438. Keywords: Flavivirus; NS3 helicase; Japanese encephalitis virus; ADME/Tox study; Niclosamide derivatives. INTRODUCTION Japanese encephalitis virus JEV is the most important cause of viral encephalitis in Asia. It is a mosquito-borne flavivirus, and belongs to the same genus as dengue, yellow fever and West Nile viruses. JEV was first reported in Japan in the 1871. It primarily affects children, a literature review estimates nearly 68,000 clinical cases of JE occur globally each year, with approximately 13,600 to 20,400 deaths (WHO, 2015). JEV has spread to most countries in south, east and southeast Asia (Mackenzie et al., 2007). Several flavivirus non-structural (NS) proteins, such as NS2B-NS3, NS3 helicase, NS4B, NS5 methyltransferase, and NS5 RNA-dependent RNA polymerase (RdRp), have been identified as potential anti-viral drug targets (Luo et al., 2015; Xie et al., 2015; Lim et al., 2015). Many compounds have an inhibitory effect on the virus, www.ijsir.co.in

raising hopes that new treatments are on the horizon for prevention and treatment of flavivirus-associated diseases (Lim et al., 2013). Vaccination can prevent the disease, but no specific antiviral drug is yet available for clinical therapy, and the death rate caused by JEV can reach as high as 60%. The NS3 protein of JEV is a large multifunctional protein possessing protease, helicase, and nucleoside 5'-triphosphatase (NTPase) activities, and plays important roles in the processing of a viral polyprotein and replication. JEV helicase is composed of three domains containg a tunnel large enough to accommodate single-stranded RNA. Each of the motifs I, II and VI was composed of an NTPbinding pocket. Mutation analyses revealed that all of the residues in I (GLY199, LYS200 and THR201), in addition to the polar residues within 47


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the NTP-binding pocket (GLN457, ARG461 and ARG464), and also ARG458 in the outside of the pocket in the motif IV were crucial for ATPase and helicase activities and virus replication (Yamashita et al., 2008). The C-terminus of NS3 helicase was identified as a potential drug target. In this study, we have screened Niclosamide derivatives against NS3 helicase. Niclosamide had lowest binding affinity at catalytic site region of the NS3 helicase, which is reported in our previous work (Singh et al., 2017). Further, best predicted Niclosamide derivatives of NS3 helicase of J E V were investigated for physicochemical properties, pharmacokinetic properties: human intestinal absorption (HIA), cellular permeability (Caco2), cell permeability Maden Darby Canine Kidney (MDCK), skin Permeability, plasma protein binding (PPB) and penetration of the blood-brain barrier (BBB), and toxicological: mutagenicity and carcinogenicity. MATERIALS AND METHODS Protein preparation The 3D coordinates of the Crystal Structure of Catalytic Domain of Japanese Encephalitis Virus NS3 Helicase/Nucleoside Triphosphatase (PDB Id: 2Z83) was retrieved from Protein Databank (http://www.rcsb.org/). Inhibitors dataset We have screened Niclosamide derivatives from pubchem compound database (Wang et al., 2010) using similar compounds, score>=95. The 3D structures of screen 37 derivatives were downloaded in .sdf format from pubchem compound database. They were later converted in .pdb format with the help of open babel tool (O'Boyle et al., 2011). Molecular docking Docking of thirty seven Niclosamide derivatives screened from PubChem comound database were done using molecular docking program AutoDock4.2 (Morris et al., 2009). Gasteiger charges are added to the ligand and maximum 6 numbers of active torsions are given to the lead compounds using AutoDock tool. Kollman charges and the solvation term were added to the protein structure. The Lamarckian genetic algorithm implemented in Autodock was used for docking. Molecular dynamics simulations 48

Molecular dynamics simulations were done using the NAMD (Phillips et al., 2005) graphical interface module incorporated in V M D (Humphrey et al., 1996). The protein-ligand complex was immersed in the center of a 50 Å box of water molecules where all water molecule atoms were closer than 1.5 Å and a CHARMM22 parameter file for proteins and lipids was used in the force field for complexes. The psf was created from the initial pdb and topology files using psfgen package of VMD. After running psfgen, two new files were generated protein.pdb and protein.psf and by accessing PSF and PDB files; NAMD generated the trajectory DCD file. After the simulations, the results were analyzed in VMD by calculating the Root mean square deviation of the complex. ADME and Toxicological properties of Niclosamide derivatives Absorption, distribution, metabolism, and excretion (ADME) and toxicological properties were essential for pharmacological/clinical applications of identified inhibitors. Therefore, The predicted inhibitors were evaluated for key physicochemical properties like molecular weight, Hydrogen Bond Donor Count, Hydrogen Bond Acceptor Count, XLogP and ADME properties like percentage of human intestinal absorption (HIA), cell permeability (PCaco-2), cell permeability Maden Darby Canine Kidney (MDCK), skin permeability, Plasma protein binding (PPB), blood brain barrier (BBB) using PreADMET tool (https://preadmet.bmdrc. k r / a d m e / ) . To x i c o l o g i c a l p r o p e r t i e s o f mutagenicity and carcinogenicity were also evaluated using PreADMET tool. RESULTS AND DISCUSSION Molecular Docking In docking studies the most important requirement was the proper orientation and conformation of ligand which fitted to the enzyme binding site appropriately and formed proteinligand complex. Therefore, optimal interactions and the best AutoDock score were used as criteria to interpret the best conformation among the 10 conformations, generated by AutoDock program. The docking results of 37 compounds with Mca model was shown in Table 1. Among the above www.ijsir.co.in


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docked compounds C I D44240996, C I D44565834 and CID88834438 had the lower binding energy -9.22 kcal/mol, -9.27 kcal/mol and -9.05 kcal/mol, even lower than Niclosamide (-8.10 kcal/mol) with NS3 helicase. Docking poses of the best conformation of CID44240996, CID44565834 and CID88834438 with NS3 helicase protein were shown in figure 1, 2 & 3. Molecular dynamics simulation After Molecular dynamics simulation, the results were analyzed in VMD by calculating the Root mean square deviation (RMSD) of the complex using rmsd.tcl source file from the Tk console and finally rmsd.dat was saved and accessed in Microsoft office excel. RSMD, a crucial parameter to analyze the equilibration of MD trajectories, is estimated for backbone atoms of the compounds CID44240996, CID44565834 and CID88834438 with NS3 helicase complex (shown in figure 4, 5 & 6). Measurements of the backbone RMSD for the complex provided insights into the conformational stability. ADME and Toxicological properties of best predicted Niclosamide derivatives In analyzing the parameters of the best predicted compounds was observed that all had values within Lipinski parameters, except XlogP to evaluate oral absorption (table2). It was observed that the compounds CID44565834, CID44240996, CID88834438 had human intestinal absorption (HIA) values in the range 90.820693 to 95.072513 (table3). These compounds are categories as in the range of well absorbed compounds (HIA: 70 ~ 100 %) (Yee, 1997). The cell permeability in vitro Caco-2 is an important test to assess intestinal absorption of drugs. It was found that the PCaCO2 (nm/s) value were 11.1689 nm/s to 17.4262 nm/s for compounds (table 3). PCaCO2 value of compounds was in low range (Yazdanian et al., 1998). The cell permeability in vitro in MDCK system is used as a tool for the rapid analysis of permeability. These derivatives had 0.0714057 nm/s to 5.05717 nm/s as low MDCK (Irvine et al., 1999) (table 3). Skin permeability parameter is used in the pharmaceutical industry to assess the risk chemical

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products in case there is accidental contact with skin (Singh and Singh, 1993). Predicted derivatives showed negative perme-ability values (table3). The binding of drug to blood and plasma proteins can alter the half-life of the drug in the body of the individual (Godin, 1995; Pratt and Taylor, 1990). It is verified that derivatives bind strongly to plasma proteins, being 58.605579 to 100.00000%. (table 4). The blood-brain barrier (BBB) has an importance in the pharmacology of drugs, because the compounds are classified as inactive and active compounds. Derivatives bind strongly to plasma proteins. In relation to the penetration of the blood-brain barrier the inhibitors analyzed showed penetration values less than 1, and ranged from 0.0731198 to 0.411246. The Ames test (Ames et al., 1972) showed compounds were mutagen and carcinogenicity in mouse and rat showed negative value. Except compound CID88834438 shows positive value in rat. CONCLUSION We got three best predicted compounds C I D 44240996, C I D 44565834 and C I D 88834438 having lower binding energy even lower than Niclosa-mide. Molecular dynamics simulations showed that predicted compounds were stable. In Silico ADME and Toxicological properties of predicted compounds showed satisfactory results. Therefore it is predicted that compounds CID44240996, CID44565834 and CID88834438 could be promising inhibitor for NS3 helicase as drug target yet experimental studies have to confirm it. ACKNOWLEDGEMENT The Authors gratefully acknowledge the necessary computational facilities and constant supervision provided by Department of Biotechnology, Rama University of Technology and Science, Kanpur, U.P., India for their generous support during the research work. CONFLICT OF INTEREST The authors declare that they have no conflict of interest.

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Table 1: Docking of Niclosamide derivatives with NS3 helicase protein. Sl. No. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37

PubChem CID 189036 487721 828117 2781466 2844786 2946176 3353792 3491605 3895545 10093194 11200749 11440508 12220828 12363049 18452502 19027407 19027409 19027410 25217041 25217042 25217043 25217045 25217155 25217156 25217270 25217492 25217494 29557196 44240996 44565834 68168508 68169781 71459109 71720820 86251702 88834438 25217274

BE -7.14 -8.39 -8.28 -8.46 -5.92 -6.54 -6.81 -6.55 -8.42 -7.66 -7.12 -6.67 -7.4 -7.92 -6.96 -7.37 -7.63 -7.99 -7.56 -8.34 -6.06 -7.28 -7.26 -7.38 -7.22 -8.32 -7.62 -8.34 -9.22 -9.27 -7.54 -8.11 -8.0 -8.63 -8.03 -9.05 -7.69

IME -9.82 -9.58 -9.47 -9.66 -8.31 -8.93 -9.19 -9.23 -9.61 -10.34 -9.5 -9.35 -10.08 -9.11 -8.45 -8.87 -9.13 -9.48 -8.75 -9.53 -7.25 -8.47 -8.45 -8.57 -8.41 -9.52 -8.81 -9.53 -10.42 -10.46 -8.73 -9.3 -9.19 -10.13 -9.22 -10.24 -8.88

IE -2.7 -1.32 -1.28 -0.68 -1.62 -1.63 -1.52 -2.76 -1.32 -2.81 -1.7 -3.21 -1.69 -1.31 -1.41 -1.42 -1.31 -1.31 -1.05 -0.97 -0.88 -1.03 -1.01 -1.0 -1.02 -1.11 -1.12 -1.11 -0.73 -0.91 -0.87 -1.04 -0.74 -1.43 -1.08 -1.14 -0.7

TorE 2.68 1.19 1.19 1.19 2.39 2.39 2.39 2.68 1.19 2.68 2.39 2.68 2.68 1.19 1.49 1.49 1.49 1.49 1.19 1.19 1.19 1.19 1.19 1.19 1.19 1.19 1.19 1.19 1.19 1.19 1.19 1.19 1.19 1.49 1.19 1.19 1.19

VdwE -9.73 -7.67 -8.28 -7.04 -6.9 -7.12 -8.59 -8.8 -8.82 -8.71 -8.63 -8.0 -8.38 -7.63 -6.87 -7.38 -8.29 -8.1 -7.7 -7.99 -6.4 -6.61 -7.5 -7.91 -6.7 -8.63 -7.76 -8.19 -8.28 -8.25 -7.76 -7.59 -7.15 -9.49 -7.51 -9.03 -6.76

EE -0.09 -1.43 -1.18 -2.61 -1.41 -1.81 -0.6 -0.43 -0.79 -1.63 -0.87 -1.36 -1.7 -1.48 -1.58 -1.48 -0.83 -1.38 -1.05 -1.54 -0.85 -1.86 -0.96 -0.66 -1.72 -0.89 -1.05 -1.34 -2.14 -2.21 -0.97 -1.71 -2.05 -0.64 -1.71 -1.21 -2.12

BE = Binding Energy; IME: Intermolecular Energy; IE = Internal Energy; TorE= Torsional; Energy; VdwE = vdW + Hbond + desolv Energy; EE= Electrostatic energy. Table 2: Physicochemical properties of best predicted Niclosamide derivatives. Sl.N o. 1 2 3

50

PubChem CID 44240996 44565834 88834438

Molecular Weight (g/mol) 306.702 327.117 396.001

Donor 2 2 2

Acceptor 4 4 4

logP 3.8 4 5.3

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Table 3: Absorption properties of best predicted compounds.

Derivative 1 2 3

PubChem CID

HIA (%)

44565834 44240996 88834438

90.820693 93.324583 95.072513

Absorption PCaco-2 (nm/sec) MDCK(nm/sec) 17.4262 11.1689 14.8798

Skin Permeability

5.05717 3.24464 0.0714057

-4.47326 -3.12468 -2.80936

Table 4: Distribution properties in percentages of PPB and penetration of the blood brain barrier of best predicted compounds.

Derivative 1 2 3

PubChem CID 44565834 44240996 88834438

PPB (%) 58.605579 96.033057 100.000000

Distribution BBB 0.171371 0.0731198 0.411246

Table 5: Toxicological properties of mutagenicity (Ames test) and carcinogenicity (mouse and rat).

Derivative 1 2 3

CID 44565834 44240996 88834438

Ames Test Mutagen Mutagen Mutagen

Carcinogenicity Mouse Rat Negative Negative Negative Negative Negative Positive

Figure 1: Docking orientation of compound CID44565834 with NS3 protein. www.ijsir.co.in

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Figure 2: Docking orientation of compound CID44240996 with NS3 protein.

Figure 3: Docking orientation of compound CID88834438 with NS3 protein. 52

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Figure 4: Graph displaying root mean square deviation (RMSD) of CID44240996 - NS3 helicase complex versus time (ps) at 310 K, resulted in highest peak at 1.149 Å.

Figure 5: Graph displaying root mean square deviation (RMSD) of CID44565834 – NS3 helicase complex versus time (ps) at 310 K, resulted in highest peak at 1.160 Å.

Figure 6: Graph displaying root mean square deviation (RMSD) of CID 88834438 – NS3 helicase complex versus time (ps) at 310 K, resulted in highest peak at 1.128 Å. www.ijsir.co.in

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REFERENCES 1. Ames B.N., Gurney E.G., Miller J.A., Bartsch H. Carcinogens as Frame shift Mutagens: Metabolites and Derivatives of 2Acetylaminofluorene and Other Aromatic Amine Carcinogens. Proceedings of the National Academy of Sciences of the United States of America 1972; 69:3128-3132. 2. Godin D.V. Pharmacokinetics: Disposition and Metabolism of Drugs. In: Munson, P.L., R. A. Mueller, G.R. Breese, Eds., Principles of Pharmacology: Basic Concepts and Clinical Applications, Chapman and Hall, New York 1995; 39-84. 3. Humphrey W., Dalke A., Schulten K. VMD: visual molecular dynamics. J Mol Graph. 1996; 14(1):33-8. 4. Irvine J.D., Takahashi L., Lockhart K., Cheong J., Tolan J.W., Selick H.E., Grove J.R. MDCK (Madin-Darby Canine Kidney) Cells: A Tool for Membrane Permeability Screening. Journal of Pharmaceutical Sciences 1999; 88:28-33. 5. Lim S. P. et al. Ten years of dengue drug discovery: Progress and prospects. Antivir Res. 2013; 100:500–519. 6. Lim S.P., Noble C.G., Shi P.Y. The dengue virus NS5 protein as a target for drug discovery. Antivir Res. 2015; 119:57–67. 7. Luo D.H., Vasudevan S.G., Lescar, J. The flavivirus NS2B-NS3 protease-helicase as a target for antiviral drug development. Antivir Res. 2015; 118:148–158. 8. Mackenzie J.S., Williams D.T., Smith D.W. Japanese Encephalitis Virus: The Geographic Distribution, Incidence, and Spread of a Virus with a Propensity to Emerge in New Areas. Persp Med V 2007; 16:201–268. 9. Morris G.M., Huey R., Lindstrom W., Sanner M.F., Belew R.K., Goodsell D.S., Olson A.J. Autodock4 and AutoDockTools4: automated docking with selective receptor flexiblity. J. Computational Chemistry 2009; 16:2785-91. 10. O'Boyle N.M., Banck M., James C.A., Morley C., Vandermeersch T., Hutchison G.R. Open Babel: An open chemical toolbox. J Chemin-

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form. 2011; 3:33. 11. Phillips J.C., Braun R., Wang W., Gumbart J., Tajkhorshid E., Villa E., Chipot C., Skeel R.D., Kalé L., Schulten K. Scalable molecular dynamics with NAMD. J Comput Chem. 2005; 16:1781-802. 12. Pratt W.B., Taylor P. Principles of Drug Action: The Basis of Pharmacology. 3th Edition, Churchill Livingstone, New York, 1990. 13. Singh A., Kumar A., Srivastava V. Molecular docking studies of antiviral drugs against NS3 helicase of japanese encephalitis virus. International Journal of Scientific and Innovative Research 2017; 5(1): 33-36. 14. Singh S., Singh J. Transdermal Drug Delivery by Passive Diffusion and Iontophoresis: A Review. Medicinal Research Reviews 1993; 13:569-621. 15. Wang Y., Bolton E., Dracheva S., Karapetyan K., Shoemaker B.A., Suzek T.O. et al. An overview of the PubChem BioAssay resource. Nucleic Acids Res. 2010; 38:D255-D266. 16. WHO. http://www.who.int/mediacentre/ factsheets/fs386/en/. Accessed on December 2015. 17. Xie X.P., Zou J., Wang Q.Y., Shi P.Y. Targeting dengue virus N S4B protein for drug discovery. Antivir Res. 2015; 118:39–45. 18. Yamashita T., Unno H., Mori Y., Tani H., Moriishi K., Takamizawa A., Agoh M., Tsukihara T., Matsuura Y. Crystal structure of the catalytic domain of Japanese encephalitis virus NS3 helicase/nucleoside triphosphatase at a resolution of 1.8 A. Virology 2008; 373(2):426-36. 19. Yazdanian M., Glynn S.L., Wright J.L., Hawi A. Correlating partitioning and caco-2 cell permeability of structurally diverse small molecular weight compounds. Pharm Res. 1998; 15(9):1490-4. 20. Yee S. In vitro permeability across Caco-2 cells (colonic) can predict in vivo (small intestinal) absorption in man--fact or myth. Pharm Res.1997; 14(6):763-6.

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EFFECT OF PLANT EXTRACTS ON MOSQUITO POPULATION *K. Singh and S. Nandan Department of Zoology, University of Lucknow, Lucknow, Uttar Pradesh , India *Address for correspondence : Dr. Kalpana Singh, Assistant Professor, Department of Zoology, University of Lucknow, Lucknow, Uttar Pradesh, India Email ID: drkalpanasingh@gmail.com ABSTRACT Mosquito population increases exponentially that is vast trouble for many nations because they transmit diseasessuch asmalaria, dengue, filaria, yellow fever, chikungunya, Japanese encephalitis, Lyme disease and epidemic poly-arthritis. There are about 3500 species of mosquitoes present in tropical or sub-tropical regions. World Health Organisation has declared mosquito as “Public enemy number one”.Use of chemical pesticides to manage mosquito menace has proved to be hazardous for human health and environmental well-being. Many plant extracts have been found to be effective against mosquito population (larval, adult as well as eggs). The present study reviews effect of various medicinal plant extract to manage mosquito population. Different herbal plant extracts dissolved in oil or other solutions has been used against mosquito larvae effectively. Keywords: Mosquito; Medicinal Plant; Plant Extract; Culex; Anopheles; Aedes INTRODUCTION Mosquitoes belonging to Order Diptera of Class Insecta of Arthropods are vectors of many diseases. Mosquitoes are responsible for transmission of many viral, bacterial and [1] protozoans' diseases. Population of mosquitoincreases exponentially casing major trouble for many countries by spreading diseases like filaria, Japanese encephalitis, Lyme disease, malaria, dengue, yellow fever, chikungunya and epidemic [2] poly-arthritis. There are about 3500 species of mosquitoes present in tropical and sub-tropical [3] region. WHO has declared mosquito as “Public enemy number one” because they transmit most dreadful diseases.[4]Out of all mosquito species, Aedes,Anophelesand Culexare major vectors. Aedesis responsible for spreading dengue, chikungunya and yellow fever. Anophelesspreadsmainlyfilariasis and malaria while Culexacts as vector for Japanese encephalitis and chikungunya.[5]The disease dengue, chikungunya which is caused by Aedes vector affects the 2.5 million people every [6] year. The breeding places of Aedes mosquito vectors are major cause of increasing dengue fever. This is because of greater urbanization and [7] growth of population. . Malaria caused by www.ijsir.co.in

Anopheles vector increasing 200 million-450 million infections annually worldwide.[8]Culexis the vector of Japanese encephalitis which happens in children with malnutrition. Major cause of [9] encephalopathy is encephalitis . There are several methods available to protect us from mosquitoes biting like physical control methods such as clearing the stagnant water and chemical control methods such as use of repellents to kill mosquitoes. The usual commercially available synthetic chemical mosquito repellent comprises Deet (N, N-diethyl-3-methyl benzamide) which hasdepicted excellent protection against mosquitoes. [10]Physical control methods are tiresome in use and chemicals used in chemical control methods have caused major environmental and health problems. However there are natural products that have proved to be effective against mosquito adult and larval population. These natural plant repellentsare the best method for protecting against the mosquito vectors because they are safe, economical and ecofriendly. Scientific researchers have searched and studied plant products like plant extracts, [11] essential oils and powder. Traditional repellent like smoke are used in the rural areas. Several 55


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plant crude extracts and compounds from many different families and plants have been screenedas [12] potentlarvicides. Researchers have established the effectiveness of plant derived secondary [13] [14] compounds, like steroids , saponin, essential [15] [16] oil, isoflavonoids , alkaloids and tannins [17] against mosquito larvae. Essential oils and plant compounds are serving as alternative root of mosquito repellent agents.[18]Taking in view the upsurge in popularity of these plant based natural products against mosquito population we tried to summarise the efficacy of these products against larval and adult population of three common mosquito vectors viz. Aedes,Anopheles and Culexin present review. EFFECT OF MEDICINAL PLANT EXTRACTS ON AEDES POPULATION Aedesaegyptiand Aedesalbopictus is the major vector for dengue and chikungunya diseases. In January and August of 2010, high dengue alert was there across India as well as in Malaysia, referable to the total deaths management because larvae were found in specific areas and more than 103 people were critically affected.[19] Chikungunya and Dengue Fever (DF) / Dengue Hemorrhagic Fever (DHF) were described from different part of India.[20, 21]There are several methods for holding Aedes mosquito vector population under check. Components of plant may be possible substitute for chemical pesticide and several plants were found to have an effect on growth, behaviour and development of [5] mosquito vector. Azadirachtasiamensis(Thai neem) shows the better efficacy against the Aedesaegypti larvae. It is found in Thailand and may be different species than the Azadirachta[22] indica (Indian neem) . To measure the efficacy of A.siamensis oil emulsion and an alginate bead th of A.siamensis oil against the IV instar larvae of Aedesaegypti were tested. Oil emulsion demonstrated greater larvicidal activity than the alginate bead oil preparation at 12 to 60 hours post-exposure (p-value <0.01). Neem oil shows 100% mortality at 48 hours and alginate bead oil formulation shows 98% mortality at 84 hours and shows 100% mortality at 96 hours against the fourth instar larvae of Ae.aegypti. Different parts of A.indica(Neem) bark, leaf, root and stem also demonstrated a good effect on mosquito vector 56

Ae.aegypti larvae. The secondary compounds of Neem have demonstrated insecticidal properties. [23] Different parts of Neem such as bark, leaf, root and seedhave been extracted with different solvent viz. acetone, chloroform and ethanol. 1mL of DMSO (dimethyl sulphoxide) was applied to solubilise extracts in water. Data were measured and LC50 and LC90 values were studied. The crude extracts were deviated and the LC50 and LC90 value limits from 50 to 837.5 ppm and 94 to 950 ppm. Experiment demonstrated that leaf acetone extract and root chloroform extract were more toxic and cause 100% mortality in 24 hours at concentration of 1000 ppm. Other extracts demonstrated 100% mortality at 48 hours. The fruits of Sapindusemarginatus and Holothuriaatra also used against the mosquito vector Ae.aegypti.Sapindusemarginatus is a medicinal plant which is widely circulated in the dry-zone of Sri Lanka. H.atra is having medicinal [24] values. The crude extracts of S.emarginatus (a medicinal plant) and the skin of H.atrahave been ........... 3 used against Ae.aegypti. Bioassay investigation was expressed with crude extracts of fruit S.emarginatusthat were extracted with the solvent ethanol disclosed LC50and LC90 values of 92.9 and 152.6 ppm. The skin extracts of H.atra were extracted with the solvent methanol disclosed LC50 and LC90 values of 68.82 and 180.76 ppm. Both the extracts were positive because the presence of Saponin. The investigation on plant Pongamiapinnataand A.indica seed oil against vector was carried out.[25]Combination of seed oil repellent also used on mosquito Ae.aegypti.The repellent were developed into 3 group's seed oils with petroleum ether, combination of seed oil, seed oil with carrier oil (Coconut oil, Olive oiland Mustard oil). Their combination ratios were 1:1, 2:1 1:2 at the concentration of 1 and 5%. Results demonstrated that 5% formulation combination of oils P. pinnata and A. Indicaat the ratio of 1:1 , the protection time was 300 and biting percentage rate of 6. At 5% concentration of P. pinnata and A.indicaseed oil in mustard oil base provided 86.36% and 85% protection time of 230 and 240 minute respectively. The study supports that P. pinnata and A.indicaishaving a good repellent potential. Different medicinal plant species aqueous extracts were used for the prevention of mosquito www.ijsir.co.in


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Ae.albopictus. The plant species and the part used were Ocimumgratissimum Whole plant, Adhatodavasica Leaf, Averrhoabilimbi Fruit, Aeglemarmelos Leaf, Careyaarborea Fruit, Commelinadiffusa Leaf, Lantana camara Flower, Phyllanthusemblica Dry seed, Scorparisdulis Whole part, Terminaliachebula Dry seed. The effect of respective plant extracts on mosquito larvae displayed to 96 hrs. Out of 10 plants O.gratissimum (whole plant) and T.chebula (Dry seed) found 100% mortality. P.emblica (Dry seed), L.camara(Flower) and A.marmelos (Leaf) expressed 95, 90 and 55% larvicidalproperties. Leaf extracts of Adhatodavasica, Commelinadiffusa fruit extracts of Averrhoabilimbi, Careyaarborea and whole plant extracts of [26 Scorparisdulisexhibited no larvicidal efficacy. EFFECT OF MEDICINAL PLANT EXTRACTS ON ANOPHELES ] POPULATION A single most important disease inflicted [27, 28] bymosquito vector is malaria and it is a major [29, 30] cause of infant mortality rate. The biggest challenge in battle against this pandemic isresistance of the parasite to anti-malarial drugs and their toxicity to human health and high treatment cost. Recent WHO calculates are that there are 300-500 million cases per year.[31, 32] Anolphelesgambiae are very notorious vector of the parasite. [29, 30]There is no vaccine to control infection caused by mosquito vector An.gambiae. To avoid this problem vector control is a best alternative. A large number of plant derivatives have established to be effective against [33] mosquitoes. A recent researcher has concentrated on plant product alternative.There are several varieties of plants present all over the world that can be used against malarial vector Anopheles.Clausenaanisata is a plant which demonstrates bioactivity against various diseases and inhibits the larvicidal activity. C.anisata belongs to family Rutaceae and originates in tropical region. The extracts of plant C. anisata were extracted with the solvent Hexane, Ethyl acetate, Chloroform, Acetone and Methanol and oils were received by hydro-distillation in qualified Clevenger-type of newly whole plant. The oils of C.anisata demonstrate markedly increased activity againstIIIrd instar larvae of www.ijsir.co.in

An.gambiae. In this study the plant C.anisata crude ethyl acetate gave higher LC50 value of -1 -1 2095.46 mg L and LC99 value of 4438.75 mg L . -1 The C.anisata oils gave LC50 value of 76.96 mg L -1 and LC99 value of 256.80 mg L . These essential oils (volatile) and crude extracts (Non-volatile) compounds of plant C.anisata are helpful in malaria and mosquito management programmes. Different types of oils extracted from plants act as potent repellent for mosquitoes.[34]The repellent action of plant Cymbopogan martini martini Stapfvarsofia oil against mosquito vector Anopheles sundaicuswas studied.Pure oil of varsofia was received from Plant Genetic Resource Division, Indian Agriculture Research Institute, New Delhi. C.martiniioil supplies 98.7 % protection in indoor and outdoor protection gives 96.52% against the vector An.sundaicus.The plant extracts of Artemisia parviflora are very effective against vector Anopheles stephensi. This plant prevents malaria in tribal village. The extracts of plant are extracted with the methanol ........... 3 solvent. The mortality rate of larvae and pupae was recorded at LC 50 and LC 90 values. The A.parviflora plant is biologically active which may be due to the presence of dynamic compounds like a-Caryophyllene, Camphor, germacrene D, Artemisia ketone,1-8 Cineole, DCopaene and Sabinyl acetate. These active compounds are poisonous against the mosquito. The LC50 measure for first instar larvae is 45.61 and is modified in the fourth instar larvae as 59.60.Eucalyptus based repellent (PMD) pmenthane-3, 8 diol was evaluated in the field comparison with Deet(N, N-diethyl-3-methyl benzamide). According to Trigg and Hill(1996) [35] this compound is nearly as effective as Deet against An.gambiae Gills. But in their study field comparison of PMD against two malaria mosquito vectors, An.funestus and An.gambiae was was investigated.Three formulation of PMD (50% AI), a pump spray, a stick, and a gel were assessed. These repellent were applied to the legs and feet at doses chosen in this experiment and they gave complete security from biting for between 6 and 7.75 hour and it depends on their formulation type. Neem products are also very helpful for controlling Malaria vector, An.stephensi.Larvicidal, Repellent, and Smoke 57


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toxicity effect of neem products is well demonstrated. Each component of neem tree has [36, 37, 38] insecticidal properties. Neem seeds comprising 99 biologically active components like azadirachtin, nimbin, nimbolidesand nimbidin. Some these derived products have ovicidal activity, antifeedancy, fecundity suppression following insect growth regulation and repellency against vector insect . [39, 40]Six neemlemonoids (purity>99%), such as azadirachtin, salannin, gedunin, deacetylgedunin, 17-hydroxyazadiradione and deacetynimbin can be chemically extracted.Larvicidal bio-assays were carried in the laboratory with neemleminoids at the lethal concentration of LC50 and LC90.Repellency test was acted by human volunteers by usingneem oil. Smoke toxicity was function on adult Anopheles female mosquito in laboratory by using neem kernels. The LC 50 and ...... 1 LC90 values of Azadirachtin treatment at 0.05, 1.0 and 1.5 ppm concentration were 0.299% and 1.061%. After the neem oil treatment at concentration 0.05, 1.0 and 1.5 ppm LC50and LC90 values were 0.503 and 1.324 respectively. Salanninwas 0.438% and 1.420%, Gedunin was 0.558% and 1.568%, Deacetylgeduninwas 0.461% and 1.384, 17-Hydroxyazadiradione was 0.387% and 1.553%, Deacetylnimbin was 0.594% and 1.542% respectively.The repellent activity of neem products was tested at different concentrations (0.2 %, 0.4 %, and 0.6 %). The products of neem oils are Azadirachtin, Salannin, 17-Hydroxyazadiradione, Deacetylgedunin, Deacetylnimbin and Gedunin.Neem oil demonstrated higher repellency (<300 minutes at 0.6 concentration) complied by Gedunin which expressed less activity (<200 minutes at 0.6 concentration).For Smoke repellency test leaves and pods were applied. When smoke emerged from leaves pods had possible powerful effect and percentage of repellency on leaf was 59% and pod was 53% and commercial oil shows positive control of 65% repellency.[41] EFFECT OF MEDICINAL PLANT EXTRACTS ON CULEX POPULATION Out of various mosquito species belonging to order Diptera, family Culicidae three important vector species are Culexpipiens, Culexquinquefasciatus, Culextritaeniorhynchus. These three 58

spread Filariasis, Japanese encephalitis and Dengue haemorrhagic fever. There are several varieties of medicinal plants which can be used as repellents for Culex species like Salvia officinalis, [42] [43] Caesalpiniapul cherrima, Tephrosia[44] [45] purpurea, Menthapulegium, Oputiadillenii, [46] Centellaasiatica, [47]Eucalyptus, Azad-irachtaindica , [48]Andrograp-hispaniculata, [49]Hyptissuaveolens[50] and Calotropis gigantean. [51] The screening

of plant S.officinalis found the phytochemicals like sterols, tannins, flavonoids, gallic tannins, catechic tannins, mucilages and glycosides components. The plant S.officinalis extracts has been extracted with Ethanol solution. The ethanoloic solution was found to be very effective with a LC50 value of 287 ppm and 487 ppm for LC90 against C.pipiens larvae. Larval mortality of C.pipiens was assessed at 600 ppm. It gives 100% mortality at the concentration of 0.5. The testing of C.pulcherrima obtained phytochemicals from the whole parts and extracted by different types of solvents like methanol, aqueous, benzene, chloroform and acetone. The testing of this plant against the mosquito vectors like C.tritaeniorhynchus, Ae.albopictusand An.sub- pictusgavefruitful results . The highest larvicidal activity was detected in benzene extract with LC50 and LC90 values were 150.47, 135.24 and 119.27 ppm and 282.57, 261.55 and 243.37 ppm respectively. [43] The testing of T.purpurea plant has been utilized in popular medicine to cover many diseases. This plant is having activities like anticancer, antioxidant, antimicrobial, anti-plasmodial, larvicidal. The extracts of plant and stem of T. purpurea were extracted with methanol solvent and tested against the Filarial vector C.quinquerd faciatus. The efficacy of stem extract against III instar larvae appeared less effective with LC50 2348 ppm than leaves extract with LC50 58.3 ppm. Leaves extracts demonstrated a greatest reduction effect on adult emergence, fecundity and fertility. Moreover, morphological deformities on pupal and adult intermediate were detected after treatment with leaves extract.[52]M. pulegium (Lamiaceae) are herbaceous plants and perennial. These plants are aromatic and are used in traditional medicine, confectionery, culinary preprations, cosmetics and perfumery.[53] After the screening of this plant the phytochemicals were www.ijsir.co.in


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obtained.The percent yield of the hydro-ethanolic extract from the arialparts (leaves, stem and roots) of Menthapulegium was 8.7±0.2. The highest larvicidal activities was detected in hydroethanolic extract of the plant M.pulegium against vector C.pipiens with the value of LC50 0.38 (0.35-0.49) and the value of LC90 0.64 (0.50-0.69) mg/ml respectively.[54]Plant based insect repellent Eucalyptus and A.indica seed oil were screened against the filarial mosquito C.quinquefasciatus. Eucalyptus oil allows longer protection other than other plant based repellents.[55]A.indica seed oil gives 90.26% and 88.83% protection and Eucalyptus seed oil gives 93.37% and 92.04% at the concentration of 50% and 100% for 4 hour [48] against Culexquinquefasciatus. The extracts of Oputiadillenii stem (modified as cladode) extracted with acetone and checked the mortality th of I V instar larvae of Ae.aegypti ......and 1 C.quinquefasciatus. The 24 hours LC50values of stem extracts of O.dillenii were estimated 10.95 ppm for C.quinquefasciatusand 21.92 ppm for [46] Ae.aegypti. After the examining of A.paniculata plant leaves extract against C.quinquefasciatusthe most effective phytochemical is andrographolide (2.39%) which is present in A.paniculata in highest amount. The plant extract is extracted with ethanol and highest mortality rate of 20% and 73.3% was shown in300 ppm at 3 and 24 hours respectively. The standardized trend was detected in toxicity of acetone extract. The highest mortality rate of 50% and 83.3% was observed in 300 ppm in 3 and 24 hours [49] respectively. H.suaveolens wasassayed for mosquito larvicidal vector C.quinque-fasciatus. It is a medicinal herb commonly known as 'American mint'.The aerial part extracts of H.suaveolens were extracted with petroleum ether, chloroform and acetone. This test revealed that acetone extract demonstrated highest larvicidal activity and LC50 value was 485.61, petroleum ether and chloroform extract showed 493.44 and 625.97 mg/L after 24 hours. In case of 48 hours petroleum ether extract ( L C 5 0 298.76mg/L) which expressed greatest larvicidal activity complied by acetone (LC50 344.03 mg/L) and chloroform (LC 5 0 429.50 mg/L). [ 5 0 ] C. gigantean (Apocynaceae) flower extracts were evaluated against filarial vector C.quinquefasciatus. The extracts were extracted with www.ijsir.co.in

petroleum ether, chloroform and ethanol.The highest repellent efficacy was shown with ethanol flower extract which allowed 100% protection in 60 2 minutes at a higher concentration of 5.0 mg/cm . Chloroform flower extracts gives 95.66% at the 2 highest concentration of 5.0 mg/cm . Petroleum ether flower extracts provided 100% at the highest concentration of 5.0 mg/cm 2 . [ 5 1 ] Shadand Andrew(2017)[56]studied larvicidal efficacy of ethanolic extracts of Annona-squamosa (Annonaceae) over the filarial vector, C.quinquefasciatus Say and found it to be effective. CONCLUSION In comparison to synthetic chemical compounds plant based products are safer. Continuous application of chemical pesticides cause insecticide resistance in mosquito's and is harmful to non-target organisms and is dangerous for environment. Whereas plant based repellents do not pose risks of toxicity to human beings and domestic animals. In many parts of the worldplant based repellents are used. Due to less effect on environment and low budget herbal plant repellents attracted great attention of community. Toxicity assay of the herbal plants need to be done before ascertaining their role in establishment.Larvicidal activities of plant extract change according to the species of plants. Plants can be substitute reference for chemical mosquito larvicides because they are having a possible source of bioactive chemicals which are ecofriendly by nature. ACKNOWLEDGEMENT Authors are grateful to Prof. Omkar, Head, Department of Zoology, University of Lucknow, Lucknow, Uttar Pradesh , India for providing laboratory facilities in the department. REFERENCES 1. Kalita B, Bora S, Sharma AK. Plant essentials oils as mosquito repellent-a review. International Journal of Research and Development in Pharmacy and Life Sciences. 2013; 3(4): 741-747. 2. Kamareddine L. The biological control of the malaria vector. Toxins. 2012; 4(3): 748-767. 3. Ghosh A, Chowdhury N, Chandra G. Plant 59


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(Verbenacea). Journal of vector Borne Diseases, 2008; 45:240-244. Chowdhurry N., Ghosh, A., Chandra, G. Mosquito larvicidal activities of Solanumvillosum berry extract against dengue vector Stegomyiaaegypti. BMC Complementary and Alternative Medicine, 2008; 8:10. Wiseman, Z., Chapagain, B.P. Larvicidal effects o f aqueous extracts of Balantiesaegyptiaca (desert date) against the larvae of Culexpipens mosquitoes. African Journal of Biotechnology, 2005; 4(11): 1351-1354. Cavalcanti, E.S.B., Morais, S.M., Lima, M.A.A., Santana, E.W.P. Larvicidal activity of essential oils from Brazillian plants against Aedesaegypti L. Memorias do Instituto Oswaldo Cruz, 2004; 99: 541-544. Joseph, C.C., Ndoile, M.M., Malima, R.C., Nakunya, M.H. Larvicidal and mosquitocidal extracts, a coumarin, isoflavonoids and pterocarpans from Neorautaneniamitis. Transactions of the Royal Society of Tropical Medicine and hygiene, 2004; 98(8): 451-455. K h a n a , V. G . , K a n n a b i r a n , K . 2 0 0 7 . Larvicidal effect of Hemidesmusindicus, Gymne-masylvestre and Eclipta prostrate against Culexquinque-fasciatus mosquito larvae. African Journal of Biotechnology, 2007; 3: 307-311. Yang, Y.C., Le, E.H., Lee, D.K., Ahn, Y.J. Repellency of aromatic medicinal plant extracts Aedesaegypti. Journal of American Mosquito Control Association, 2004; 20(2):146-149. Cruez AF (2010).265 Dengue outbreak sites declared.New Straits Times (December 3). http://my.vlex.com/vid/dengue-outbreaksites-declared-219283771. Surendran S.N., Kannathasan S., Kajatheepan A. & Jude P.J. Chikungunya-type fever outbreak: some aspects related to this new epidemic in Jaffna district, northern Sri Lanka. Tropical Medicine and Health, 2007; 35(3): 249-252.21. Kularatne S.A.M., Seneviratne S.L., Malavige G.N. & Fernando S. Synopsis of findings from recent studies on dengue in Sri Sri Lanka. Dengue Bulletin, 2006; 30: 80-86. www.ijsir.co.in


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22. Sombatsiri K, Ermel K, Schmutterer H. The Thai neem tree: Azadirachtasiamensis (Val.). In:Schmutterer H, ed. The neem tree, AzadirachtaindicaA. Juss and other malacious plants: sources of unique natural products for integrated pest management, medicine, industry and other purposes. Weinheim:VCH; 1995:585-97. 23. Obomanu FG, Ogbalu OK, Gabriel UU, Fekarurhobo GK, Adediran BI. Larvicidal properties of Lepidagathisalopecuroides and Azadirachtaindica on Anopheles gambiae and Culexquinquefasciatus. African Journal of Biotechnology. 2006 5(9): 761-765. 24. Kerr A.M. Holothuroidea Sea Cucumbers. 2000: http://tolweb.org/Holothuroidea/ 19240/2000.12.01 25. Mukesh Y, Savitri P, Kaushik R and Singh N.P. Studies on repellent activity of seed ......oils 1 alone and in combination on mosquito, Aedesaegypti. Journal of Environmental Biology, 2014; 35: 917-922. 26. Rathy M.C, Sajith U and Harilal C.C. Larvicidal efficacy of medicinal plant extracts against the vector mosquito Aedesalbopictus. International Journal of Mosquito Research. 2015; 2 (2): 80-82. 27. Sachs J, Malaney P. The economic and social burden of malaria. Nature. 2002; 415(6872): 680-685. 28. Martenes P, Kovats RS, Nijhof S, de Vries P, Livermore MTJ, Bradley DJ, et al. Climate change and future populations at risk of malaria. Global Environmental Change. 1999; 9(1): S89-S107. 29. Hwang UW. Revisited ITS2 phylogeny of Anopheles (Anopheles) Hyrcanus group mosquitoes: reexaminaton of unidentified & misidentified ITS2 sequences. Parasitology Research. 2007; 101(4):885-894. 30. Geng YJ, Gao ST, Huang DN, Zhao YR, Liu JP, Li XH, et al. Differentially expressed genes between female and male adult Anopheles anthropophagus. Parasitology Research 2009; 105(3): 843-851. 31. Kumar A, Valecha N, Jain T, Dash AP. Burden of Malaria in India: Retrospective and Prospective View. The Amarican Journal of Tropical Medicine and Hygine. 2007; 77(6):69-78. www.ijsir.co.in

32. World Health Organisation. World malaria report 2010: Geneva, 2010. 33. El- Hag EA, El Nadi AH, Zaitoon AA. Toxic and growth retarding effects of three plant extracts on Culexpipiens larvae (Diptera: Culicidae). Phytotherapy Research, 1999; 13(5): 388-392. 34. Curtis CF, Lines JD, Baolin Lu, Renz A. Natural and synthetic repellents. In: Curtis CF, editor. Appropriate technology in vector control. Boca Raton, Florida, CRC Press Inc, 1990; p. 75-92. 35. Trigg, J. K. and N. Hill. Laboratory evaluation of eucalyptus-based repellent against four biting arthropods. Phytotherapy Research. 1996; 10(4): 313-316. 36. Murugan, K., Senthilkumar, N., Babu, R. and Senthil Nathan, S., 1995. Antifeedant and ovipositionaldetterent effects of excudates of (Azadirachtinindica A. Juss). Neem Newsletter. 1995; 12(4): 43-44. 37. Murugan, K. and Jayabalan, D., 1995. Antifeedent and ovipositionaldetterent effects of neem root extract (Azadirachtinindica A. Juss). Neem Newsletter. 1995; 12 (4): 45-46. 38. Murugan, K., Sivaramakrishnan, S., Senthil Kumar, N., Jayabalan, D. and Senthil Nathan, S. Potentiating Effects of Neem on Nucleopolyhedrovirus Treatment of Spodopte-ralitura Fabaceae. International Journal of Tropical Insect Sciences. 1999; 19: 2-3. 39. Isman, MB. Botanical insecticides, deterrent and repellents in modern agriculture and an increasingly regulated world. Annual Review of Entomic. 2006; 51:45-66. 40. Schmutterer, H. Properties of natural pesticides from the neem tree, Azadirachtaindica. Annual Review of Entomol. 1990; 35:271-297. 41. Murugan K, James Pitchai G, Madhiyazhagan P, Nataraj T, Nareshkumar A, Jiangh-Shiou Hwang, R. Chandrasekar, Nicoletti M, Amsath A and RanjeetBhagooli. Larvicidal, Repellent and Smoke Toxicity effect of Neem products against Malarial vector, Anopheles stephensi. International Journal of Pure and Applied Zoology. Volume 2, Issue 2, pp: 2014; 71-83. 42. El Ouali Lalami Abdelhakim, El-Akhal 61


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Fouad, EzZoubiYassine, Taghzouti Khalid. Phytochemical Screening and Larvicidal Efficacy of Ethanolic Extract of Salvia officinalis (Lamiaceae) from North Center of Morocco Against Culexpipiens (Diptera: Culicidae) Vector of Serious Human Diseases. International Journal of Pharmacognosy and Phytochemical Research. 2016; 8(10); 1663-1668. Govindarajan M, Rajeswary M, and Amsath A.Larvicidal properties of Caesalpiniapulcherrima (Family: Fabaceae) against Culextritaeniorhynchus, Aedesalbopictus and Anopheles subpictus (Diptera: Culicidae). International Journal of Pure Applied Zoology. 2013; 1(1): 15-23. Tarek M.Y. El-Sheikh and Naglaa M. Shalaby. Evaluation of the Toxicity Effect of Tephrosiapurpurea Extracts against Filarial Vector Culexquinquefasciatus. Asian Journal of Applied Sciences. 2014; 2(1). Fouad El-Akhal, YassineEzzoubi, Khadija Essafi, Abdelhakim El OualiLalami. Qualitative Phytochemicals Analysis and Larvicidal Activity of Hydro- Ethanolic Extract of Moroccan Menthapulegium Against Larvae Mosquito Culexpipiens (Diptera: Culicidae) Vector of Infectious Diseases. International Journal of Pharmaceutical and Clinical Research. 2016; 8(10): 1402-1406. Devadass R, Guruswami P, and Rajamani R.K. Effects of stem (modified as cladode) extract of Oputiadillenii on the survival and development of fourth instar larvae of Culexquinquefasciatus and Aedesaegypti. International Journal of Biosciences and Nanosciences: 2016; 3 (2), 25-28. Rajkumar, S and Jebanesan, A. Larvicidal and Adult Emergence Inhibition Effect of Centellaasiatica Brahmi (Umbellifera) against Mosquito Culexquinquefasiatus Say (Diptera: Culicidae). African Journal of Biomedical Research. 2006, 8; 31-33. Shyamapada M. Repellent activity of Eucalyptus and Azadirachtaindica seed oil against the filarial mosquito Culexquinquefasciatus Say (Diptera: Culicidae) in India. Asian Pacific Journal of Tropical Bio-

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Larvicidal activity of Andrographispaniculata (Burm.f) Nees against Culexquinquefasciatus Say (Insecta: DipteraCulicidae), a filarial vector. Asian Pacific Journal of Tropical Disease. 2012; S574S578. Sakthivadivel M, Gunasekaran P, Sivakumar M, Arivoli S, Raveen R.S and Tennyson S. Mosquito larvicidal activity of Hyptissuaveolens (L.) Poit (Lamiaceae) aerial extracts against the filarial vector Culexquinquefasciatus Say (Diptera: Culicidae). Journal of Medicinal Plants Studies. 2015; 3(4): 1-5. Dhivya R, Manimegalai K. Mosquito repellent activity of Calotropisgigantea (Apocynaceae) flower extracts against the filarial vector Culexquinquefasciatus. Hygeia Journal of Drugs and Medicine.2013; 5(2): 56-62. Touqeer, S., Saeed M.A. and Ajaib, M. (2013): A Review on the Phytoche-mistry and Pharmacology of Genus Tephrosia. Phytopharmacology .2013; 4(3), 598-637. Brada M, Bezzina M, Marlier M, Carlier A, Lognay G. Variability of the chemical composition of Mentharotundifolia from Northern Algeria. Biotechnology, Agronomy, Society and Environment. 2007; 11(1): 3-7. Fouad El-Akhal, YassineEzzoubi, Khadija Essafi, Abdelhakim El OualiLalami. Qualitative Phytochemicals Analysis and Larvicidal Activity of Hydro- Ethanolic Extract of Moroccan Menthapulegium Against Larvae Mosquito Culexpipiens (Diptera: Culicidae) Vector of Infectious Diseases. International Journal of Pharmaceutical and Clinical Research. 2016; 8(10): 1402-1406. Fradin MS, Day JF. Comparative efficacy of insect repellents against mosquito bites. Shad A. and Andrew J. Larvicidal efficacy of ethanolic extracts of Annonasquamosa (Annonaceae) over the filarial vector, Culexquinque-fasciatus Say (Culicidae). Journal of Entomology and Zoology Studies. 2017; 5(1): 373-377. www.ijsir.co.in


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FORMULATION AND EVALUATION OF POLYHERBAL OINTMENT *Swapnil Dukare, Prajkta Gaikwad, Kolhe Shilpa Savata, S.L. Jadhav Depart of Pharmacy, Vishal Institute of Pharmaceutical Education and Research *Address for correspondence : Swapnil Dukare, Depart of Pharmacy, Vishal Institute of Pharmaceutical Education and Research, Ale Tal-Junnar Dist-Pune 412411 Ta: Junnar Dist: Pune Pincode: 412411, Maharastra, India; Email ID: swapnildukare2014@gmail.com ABSTRACT Herbal ointment containing hydroalcoholic extract of plants- psorolea corylifalia , Achryanthes aspera,was formulated as ointment and the hydroalchoholic extract was prepared by maceration method and the extract was incorporated into 10gm of simple ointment base by melting and trituration to give ointment . These formulations were evaluated for the following parameters: pH, spreadability, grittiness, skin irritation study, stability. Keywords: Herbal ointment. Bavanchi ; psorolea corylifalia, Aghada ; Achryanthes aspera ; Neem ; Turmeric ; Physical Parameters ; Phytochemicals INTRODUCTION Recently there has been a shift in universal trend from synthetic to herbal medicine, which we can say 'Return to Nature'. Medicinal plants have been known for millennia and are highly esteemed all over the world as a rich source of therapeutic agents for the prevention of diseases and aliments. Nature has bestowed our country with an enormous wealth of medicinal plants; therefore, India has been referred to as the medicinal garden of the world. The other main source of medicinal plants is from cultivation. The cultivated material is definitely more appropriate for use in the production of drugs.[1] Along with other dosage forms of herbal drugs are also available in the form of ointment which is semisolid prepration used topically for several purpose eg. as protectants ,antiseptic, antihealing, emollient, kera-

[2]

tolytic and astrigents. Bavachi consists of leaves of psorolea corylifalia familyfabaceae. Bavachi leaves is p. corylifalia or Bu GuZhi in traditional chinese medicine is an herb used to tonify the kidneys, particularly kidney yong and essence. It is used for helping the healing of bone fractures, for lower back and knee pain, [3] impotence, bed wetting, hair loss and vitiligo. Aghada consists of dried leaves of Achryanthes aspera Family- Amarantaceae. Aghada has diuretic, expectorant and purgative properties. The juice of its leaves is used in feaver, cough, diarrhea, dysentery, dropsy and other disease. Decoction prepared using the herb is used in stomach ache and bowel complaints, piles, boils, skin eruption , [4] etc.

[3]

1. Bavanchi Synonyms- Cullen Corylifolium -Lotodes Corylifoli B.S.-It is obtained from dried leaves of Psoralea Corylifolia Family- Fabaceae Chemical Constituents Flavonoids(Neobavaisoflavone,Isobavachalcone,Bavachalcone,Bavachinin, Bavachin,Corylin,Corylifol,Corylifolin and 6-Prenylnaringenin) -Coumarins (Psoralidin, Psoralen, Isopsoralen and Angelicin) -Meroterpenes (Bakuchiol and 3-Hydroxybakuchiol)-Very high concentration of Genistein

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2. Aghada [3] Synonyms- Apamarg , Aghata , Onga , Apang Madhogantha B.S.-It is obtained from dried leaves of Achryanthes Aspera Family- Amarantaceae Chemical constituenst-Triterpenois Saponins , Oleanoic Acid (Aglycone , Ecdysterone ), Hormones , Long Chain Alcohol, Achryanthine , Betaine , Pentatriaontane, Hexatriacontane, Tritriacontane .

MATERIALS AND METHOD Collection of plant material : Leaves of plants were collected from the local area of Pune. Preparation of extract : Leaves of the plant were collected and washed thoroughly with distilled water and shade dried for 10 days. Dried leaves were grind into powder form. 20 gm powder was imbibed with 350ml of 90% ethanol for 3hrs. and transferred to percolator with addition of 150ml of 90% ethanol for maceration for 7 days with occasional stirring. Finally

ethanolic extract was collected and concentrated to get blackish green residue. The extract was stored in the airtight container at cool and dark place. Preparation of extract : Dried leaves of turmeric were grind and the powder obtained was followed for extraction same as that for bavanchi leaves extract. The extract with blackish green colour was obtained and stored at cool and dark place in [5] air tight container. Formulation of ointment

Table 1: Formulation of ointment base

Sr.no 1. 2. 3. 4.

Name of Ingradient Wool fat Cetostearyl alcohol Hard paraffine Yellow soft paraffin

Table 2: Formulation of herbal ointment Sr.no Name of Ingradient

1. 2. 3. 4. 5. 6.

Prepared extract sample1 Prepared extract sample 2 Prepared extract sample 3 Prepared extract sample 4 Prepared extract sample 5 Ointment base q.s.

Procedure for preparation of herbal ointment : (a) Initially ointment base was prepared by weighing accurately grated hard paraffin which was placed in evaporating dish on water bath. After melting of hard paraffin remaining ingredients were added and stirred gently to aid melting and mixing homogeneously followed by cooling of ointment base. 64

Quantity to be taken 0.5gm 0.5gm 0.5gm 8.5gm

Quantity to be taken 0.03gm 0.03gm 0.03gm 0.03gm 0.03gm 10gm (b) Herbal ointment was prepared by mixing accurately weighed Neem and Turmeric extract to the ointment base by levigation method to prepare a smooth paste with 2 or 3 times its weight of base, gradually incorporating more base until to form homogeneous ointment, finally transferred in a suitable container. www.ijsir.co.in


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Evaluation [7 ] : Colour and Odour - Physical parameters like colour and odour were examined by visual examination. Consistency - Smooth and no greediness is observed. pH - pH of prepared herbal ointment was measured by using digital pH meter. The solution of ointment was prepared by using 100ml of distilled water and set aside for 2hrs. pH was determined in triplicate for the solution and average value was calculated. Spreadability:The spreadability was determined by placing excess of sample in between two slides which was compressed to uniform thickness by placing a definite weight for definite time. The time required to separate the two slides was measured as spreadability. Lesser the time taken for separation of two slides results better spreadability.Spreadability was calculated by following formula S=M×L/T Where, S= Spreadability M= Weight tide to the upper slide L= Length of glass slide T= Time taken to separate the slides Extrudability - The formulation was filled in collapsible tube container. The extrudability was determined in terms of weight of ointment required to extrude 0.5cm of ribbon of ointment in 10 seconds. Diffusion study : The diffusion study was carried out by preparing agar nutrient medium. A hole board at the center of medium and ointment was by placed in it. The time taken by ointment to get diffused through was noted. ( after 60 minutes)

LOD -LOD was determined by placing the formulation in petri-dish on water bath and dried for the temperature 105oC. Solubility: Soluble in boiling water, miscible with alcohol, ether, chloroform. Washability:Formulation was applied on the skin and then ease extend of washing with water was checked. Non irritancy Test : Herbal ointment prepared was applied to the skin of human being and observed for the effect. Stability study -Physical stability test of the herbal ointment was carried out for four weeks at various 0 0 0 temperature conditions like 20 C, 25 C and 37 C. The herbal ointment was found to be physically 0 0 stable at different temperature i.e. 20 C, 25 C, 0 37 C within four weeks. RESULTS AND DISCUSSION The present study was done to prepare and evaluate the herbal ointment. For this the herbal extracts were prepared by using simple maceration process to obtain a good yield of extract and there was no any harm to the chemical constituents and their activity. The levigation method was used to prepare ointment sothat uniform mixing of the herbal extract with the ointment base was occurred which was stable during the storage. The physicochemical properties were studied which shows satisfactory results for spreadability, extrudability, was hability, solubility, loss on drying and others. Also the formulation was placed for a stability study at different temperature conditions like 20 0 0 0 C, 25 C and 37 C within four weeks. There were no changes observed in spreading ability, diffusion study as well as irritant effect.

1. Results of physical characteristics:

Sr. No

Plant Name

1.

Aghada

2.

Bavanchi Green

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Obtained value Colour Green

Odour Taste Characteristic Pungent bitter Characteristic Bitter

Std. Value Colour green Green

Odour Taste Characteristic Pungent, bitter Characteristic bitter

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2.Result of Extractive value Determination:

Plant name

1. Aghada 2. Bavachi

Extractive value Alcohol solubile Extractive value 4%w/w 5%w/w

3.Result of Plant extracts preparation :

SR. No. 1.

2.

Plant Species

Part Percentage Physical characterstics Use Yield Colour Odour Taste Solubility (w/w) Achryanthes Leaf 4%w/w Green characteristic Pungent, Soluble in aspera bitter boiling water , miscible with alcohol, ether, choloform Psoralea Leaf 5%w/w green characteristic Bitter Soluble in Corylifolia boiling water , miscible with alcohol, ether, choloform

4.Result of preliminary Phytochemical screening of extract:

Sr. No. 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11.

66

Test Carbohydrate Proteins and Amino acid Alkaloids Glycosides Steroids Triterpenoids Tannis Phenolic Compounds Flavonods Saponins Vitamins

Plant extract Aghada + -

Bavachi + -

+ + + + +

+ + + + + +

+ + -

+ + -

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Physicochemical evaluation of formulated ointment : Table 3: Physicochemical evaluation of formulated ointment Physicochemical parameters observation -

Physicochemical parameters Colour Odour Consistency PH Spreadability(seconds) Extrudability Diffusion study (after 60 min) Loss on drying Solubility Washability Non irritancy Solubility study(200C,250C,370C)

Observation Greenish brown charactristic Smooth 6.5 0.26gm 0.7 cm 30% Soluble in boiling water, miscible with alcohol,ether&chloroform good Non irritant Stable

Figure 1: Dried extract of samples

Fig.2. pH www.ijsir.co.in

Fig.3: Spreadability test 67


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Fig.4: Extrudability CONCLUSION : From the ancient time Bavanchi and Aghada is used for their various medicinal properties like antihealing, antidiuretic, skin eruption, impotence, etc. Thus this ointment could become a media to use these medicinal properties effectively and easily as a simple dosage form. REFERENCES : 1. Biren shah, A. K. seth .Textbook of Pharmacognosy &Phytochemistry, published by Elsevier, a division of reed Elsevier India private limited, 1st edition 2010. 2. Cheng.xia.(2001). Easy Comprehension of Traditional Chinesemesicine, Chinese Material Medica, Canadian Institute of Traditional Chinese Medicine, page-343.

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Fig.5: Diffusion study 3.

Herbsguide.net 4. Kokate C. K., Gokhale S.B., Purohit S.P. A Textbook of Pharmath cognosy, NiraliPrakashan 34 edi.Sept 2013, 9.117. 5. S. L. Deore , S.S Khadabadi , B.A Baviskar . Pharmacognosy and Phytochemistry , A Comprehensive Approach, Pharmamed Pres a unit of BSP books pvt. Ltd. printed on 2014, page no. 483. 6. Atmaram Pawar & R.S.Gaud, Modern Dispensing Pharmacy, 2ndedtion Career Publications, 215-216 7. Shubhangi E. Sawant, Monali D. Tajane. Formulation and Evaluation of Herbal Ointment Containing Neem and Turmeric extract. Journal of Scientific and Innovative research, ISSN 2320-4818 JSIR 2016; 5(4): 149-151

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COMPARATIVE STUDY ON MATCHING CRITERION AND MOTION ESTIMATION OF ARRIVAL WAVES *Mohit Bajpai Department of Physics, Sai Nath University, Ranchi, Jharkhand , India *Address for Correspondence: Mohit Bajpai , Assistant Professor, Department of Physics, Sai Nath University, Ranchi, Jharkhand, India Email Id: mohitsky25@gmail.com

ABSTRACT The matching criterion or the distortion function is used to quantify the similarity between the target block and candidate blocks. If due to the large search area, many candidate blocks are considered, the matching criteria will be evaluated many times. Hence choice of the matching criteria has an impact on the success of the compression. If the matching criterion is slow, then the block matching will be slow. If the matching criterion results in bad matches then the quality of the compression will be adversely affected. Fortunately a number of matching criteria are suitable for use in wave compression.The paperdescribs the relation between matching criterion and block matching between arrival data. Keywords: Block data; Matchingcriterion; Wave compression;

INTRODUCTION Data processing consists of a wide variety of techniques and mathematical tools to process an input data. An data is processed as soon as we start extracting data from it. The data of interest in object recognition systems are those related to the object under investigation. An data usually goes through some enhancement steps, in order to improve the extractability of interesting data and subside other data. Extensive research has been carried out in the area of data processing over the last 30 years. Data processing has a wide area of [1,2] applications . Some of the important areas of application are business, medicine, military, and automation.Data processing has been defined as a wide variety of techniques that includes coding, filtering, enhancement, restoration registration, and analysis. In many applications, such as the recognition of three-dimensional objects, data processing and pattern recognition are not separate disciplines. Pattern recognition has been defined as a process of extracting features and [4,5] classifying objects. In every three-dimensional (3-D) object recognition system there are units for data processing and there are others for pattern recognition.There are two different approaches to wave arriving (1) Analog processing- This www.ijsir.co.in

approach is very fast since the time involved in analog-to-digital (AD) and a digital-to-analog (DA) conversion is saved. But this approach is not flexible since the manipulation of data's is very hard (2) Digital processing- This approach is slower than the analog approach but is very flexible, since manipulation is done very easily. The processing time of this approach is tremendously improved by the advent of parallel processing techniques. DIGITAL DATA ARRIVING Data processing is defined as the processing of two dimensional datas by a digital computer. A digital data is represented by an array of regularly spaced and very small quantized samples of the data. Two processes that are related to any digital system are sampling and quantization. When a picture is digitized, it is represented by regularly spaced samples of this picture .[3,6] These quantized samples are called pixels. The array of pixels that are processed in practice can be quite large. To represent an ordinary black and white television (TV) data digitally, an array of 512 × 512 pixels is required. Each pixel is represented by an 8 bit number to allow 256 gray levels. Hence 69


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a single TV picture needs about 2 × 10 bits. Digital data processing encompasses a wide variety of techniques and mathematical tools. They have been developed for use in one or the other of two basic activities that constitute digital data processing: data preprocessing and data analysis. An approach called the state-space approach has been recently used in modeling data processors.[7] These data processors are made of linear iterative circuits. The state-space model is used efficiently in data processing and data analysis. If the model of an data processor is known, the realization of a controllable and observable data processor is then very simple.The matching criterion mostly used in the literature is minimum mean absolute error, which at point (i, j) for an N x N block and search window of size ±p, is defined as ...... 1

In wave data compression, the residue frame which is calculated by taking the difference of the current and the predicted frame is coded using transform coding technique, called Discrete Cosine Transform (DCT). According to the characteristics of this transform, the number of bits required to code a smooth residue frame will be smaller than the non smooth residue frame. Therefore, X. Jing, C. Zhu and L. Chau[8] proposed a smooth constrained based MAE as block matching criteria for motion compensation to reduce the required number of bits for coding besides minimizing the total distortion. In this method, not only the MAE over the residue block is taken into consideration but also the maximum and minimum residue value error, denoted as MME, is taken care of as well. Since DCT is applied over 8x8 block, each residue block (16x16) is divided into four equal size sub blocks (8x8) and MME is calculated for each sub block

Where, −p<= i , j<= +p and c(x,y) and r(x,y) are pixel values at position (x,y) in the current and reference frame respectively. Motion vector is defined as the value of (i, j) for which MAE(i, j) is minimum. Obviously, the residue error between the predicted and actual block in the current frame should be minimum for good matching. Algorithm: Arrival pixel 2x2 pixel matching criterion In MAE based criterion, the average error value is considered while ignoring the individual error term.S. Wang and H. Chen proposed vector matching criteria for block matching to overcome this drawback. In this approach, each N x N block is represented by a vector. Further, each block is subdivided into smaller blocks of size like 2x2, which is represented by a component of the corresponding vector and MAE is calculated between each temporally adjacent sub block in the current and reference frame. A threshold value is chosen by exhaustive search and vector components (out of N2 / 4, assuming the sub block size as 2x2 having value smaller than the threshold value are counted for a given block. Finally, the block having maximum number of such vector components within the defined search area is declared to be the best matching block. Algorithm: Arrival pixel 8x8 pixel matching criterion

.......................... 2 ........... 3

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Where alpha is a weighing factor. The block which has minimum SC-MAE value in the search area, is declared as the best matched block. Algorithm: Arrival pixels matching criterion in Matrix form Though VMC and SC-MAE based methods have partially reduced the drawbacks of MAE criterion, but they are not suitable for input wave dataespecially with rotation and zoom effect. Further, the similarity measurement of blocks in VMC is dependent on the input threshold value. In this section, a new criterion for block matching is being proposed which not only removes all the shortfalls of MAE but also gives better results than VMC and SC-MAE based techniques. Let R and C are two frames of equal size (N x N) in the reference frame and current frame respectively. Further, let R = [R 1 , R 2 ....R N 2 ] and C=[C1,C2....C N2] be the pixel values in these blocks. Since the data block may have different range of pixel values along each dimension, the pixel values are redefined on the basis of the higher range of intensities in the frame. If the minimum and maximum intensity values in reference block R are Rmin and Rmax, and same for the current block are Cmin and Cmax, then the new www.ijsir.co.in


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intensity values of the reference block Rnew and Curent block Cnew are defined as given below:

The function f(|(Rnew) – (Cnew)|,τ) measures the degree of matching between (Rnew) and Cnew and the positive threshold parameter τ = max((Cmax – Cmin), (Rmax – Rmin)), determines the selection of pixels for matching purposes, i.e. for a value of |(Rnew) – (Cnew)|≤τ Finally, the location of any such block R in the reference frame in a given search window for which the value of M(R, C) is minimum, gives motion vector. RESULTS In finding the results for the different block matching criteria using three step search method for the block based search, three sample waves

have been used in this paper for comparison . The Results from all the predefined three criteria along with the proposed one are given in graphical form and also are shown using for the comparison. These experiments have been performed in terms of two parameters- average error per pixel and average search points per block on three waves. When the changes in adjacent frames are nominal, it has been observed that the proposed criterion gives the better results in comparison to that of MAD and SC-MAD. If the degree of variation in intensities of the adjacent frames is high, the proposed algorithm gives the best results, when compared with other criterions.

Figure 1.1 Comparison of Average errors per pixel for viptraffic.avi www.ijsir.co.in

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These results have been found experimentally by taking first thirty frames form these mentioned waves. Detailed results can be understood by above corresponding graphs. REFERENCES 1. H. Chung-Lin and H. Chao-Yuen, & quot; A new motion compensation method for imagesequence coding using hierarchical grid interpolation," Circuits and Systems for VideoTechnology, IEEE Transactions on, vol. 4, pp. 42-52, 1994. 2. H. Ko-Cheung and S. Wan-Chi, " Extended analysis of motion-compensatedframe difference for block-based motion prediction error," Image Processing, IEEE Transactions on, vol. 16, pp.1232-1245, 2007. 3. N. Ahmed, T. Natrajan, and K. R. Rao, "Discretecosineransform,"IEEE Trans Computers,vol. C-23, pp. 90-93, Dec 1974.

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4. M. J. Narasimha and A. M. Peterson, "On the computation of the discrete cosine transform,"IEEE Trans on Communications, vol. 26, pp. 934-926, 1978. 5. W. Pennebaker and J. Mitchell, JPEG Still Image Data Compression Standard. Van NostrandReinhold, New York, 1993. 6. G. K. Wallace, "The JPEG still picture compression standard," Consumer Electronics, IEEETransactions on, vol. 38, pp. xviii-xxxiv, 1992. 7. K. Asada, H. Ohtsubo, T. Fujihira, and T. Imaide, & quot;Development of low powerMPEG1/JPEG encode/decode IC, " Consumer Electronics, I E E E Transactions on, vol. 43, pp.639-645, 1997. 8. Jing, X., C. Zhu, and L. Chau.Subpixel edge localization and the interpolation ofstill images. I E E E Transactions on Image Processing 4(3), 285–295. (2003). DOI: 10.1109/83.366477 55

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IMPOTANCE OF COMPETENCY MAPPING INTO KNOWLEDGE MANAGEMENT *Pushpendra Dixit Department of Management, JJT University, Rajasthan, India *Address for correspondence: Pushpendra Dixit, Research Scholar, Department of Management, JJT University, Rajasthan, India Email ID:dixit@narainagroup.net ABSTRACT Organizations try to define and document project manager competencies. Many factors like a sound understanding of competencies, competency grades, facilitators' interviewing and inference skills, etc, play a very important role in such an exercise. However, there is a much greater challenge of avoiding a 'me too' mindset. The exercise must aim at bringing the best out of a project manager with honest efforts to help the PM successfully continuing the journey towards competency! The key of this paper is to go beyond mere processes and create a mapping exercise based on action oriented competency statements. Keywords: Competency; Organization; Project Management; Mapping

INTRODUCTION Competency mapping is a process of identifying key competencies for a particular position in an organization, and then using it for training and development, performance management, and sequential planning. Several companies in this emerging corporate culture have started using competency mapping tools to gather knowledge about their current as well as prospective employees. The technique depicts and shows skills and knowledge of the person, his activities in presence of others, how well he works with others, his abilities, his constitution, his dedication and his willingness to work. choing through the corridors of our organization we often hear these refrains? We plan to ire a new project manager... how can we redict which candidate will perform best?? We want to give project management training to some of our junior engineers... how can we be sure which ones are most likely to succeed at project management? ? ? We are reviewing proposals from several vendors for a project that is critical to our company's future... how can we tell if their project manager is competent? And this is not limited to chat around the coffee machine alone. These are concerns that engage senior management as well; and nd an echo in the words of the CEO who declares, "Our organization is growing by leaps and bounds in all aspects such as manpower, clients, revenue, www.ijsir.co.in

locations, certications and benchmarking. We need to prepare our middle management for executing and managing large, x bid and new clients' projects. The key parameter is to implement a pool of competent project managers/leaders and mentor the SPM / PM / PL while improving their PM competencies. COMPETENCY MAPPING A competency mapping presentation displays personality traits. The total process helps the company perform better in personnel management and interactive workplace communication. The stream of management has become indispensable over a course of time now. Experts in clinical psychology have led to develop some important characteristics of a person's competency and those are: Constitution: Personality is the outcome of a denite constitution. This constitutiondenesthe abilityof the person to work as a team member, a team leader, an individual, and evenhis temperament. Traits:Traits are both physical and behavioral, which differ from person to person and perspective from the eye of the management. Traits and constitution are interdependent. Self-Concept:Every individual interprets about his own traits and keeps on 73


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makingderiving the facts about him. If ideas get respect from the management in daily routine, employee becomes more productive and attains a self-satisfaction. Skill and Knowledge: Competency mapping helps the management to understand and to ndout the skills andknowledge of employees, who are distinct with approach and level ontelligence.Even a simple virtue of being patient is a rare skill that recruiters look for. Competency Mapping Denes 1. Competency standards & qualications 2. Role specic competency proles 3. Assessment methodology 4. Training provider screening & accreditation

Competency Tracking 1. Competency based training 2. Customized training courses to Suit Company & local requirements 3. Technical & vocational training 4. Safety emergency response training 5. Assessment of competency Competency Development 1. Establish training matrix 2. Gap analysis to identify individual training requirements 3. Monitor individual training currency & need for refresher training 4. Book training courses 5. Record of competency

Figure 1: Competency of Organization KNOWLEDGE MANAGEMENT Knowledge Management is the collection of processes that govern the creation, dissemination, and utilization of knowledge. In one form or another, knowledge management has been around for a very long time. Practitioners have included philosophers, priests, teachers, politicians, scribes, Liberians, etc. So if Knowledge Management is such an ageless and broad topic what role does it serve in today's Information Age? These processes exist whether we acknowledge them or 74

not and they have a profound effect on the decisions we make and the actions we take, both of which are enabled by knowledge of some type. If this is the case, and we agree that many of our decisions and actions have profound and long lasting effects, it makes sense to recognize and understand the processes that effect or actions and decision and, where possible, take steps to improve the quality of these processes and in turn improve the quality of those actions and decisions for which we are responsible? www.ijsir.co.in


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Knowledge management is not a, "a technology thing" or a, "computer thing" If we accept the premise that knowledge management is concerned with the entire process of discovery and creation of knowledge, dissemination of

knowledge, and the utilization of knowledge then we are strongly driven to accept that knowledge management is much more than a "technology thing" and that elements of it exist in each of our jobs.

Figure 2.0: Hierarchy of competency It is a subject concerned of managing knowledge, amplifying knowledge through different

resources. It is not an end but a beginning of a journey to reach the following trail:

Figure3.0 Knowledge management www.ijsir.co.in

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1. Gathering facts. 2. Moderate structured approach. 3. Working prole system. 4. Improving performance competitive advantage. 5. Retaining intellectual capital. 6. Creating feedback. 7. Adopting changes in environment and markets. IMPORTANCE OF COMPETENCY The value of competency mapping and identifying emotional strengths is that many employers now purposefully screen employees to hire people with specic competencies. They may need to hire someone who can be an effective time leader or who has demonstrated great active listening skills. Alternately, they may need someone who enjoys taking initiative or someone who is very good at taking direction. When individuals must seek new jobs, knowing one's competencies can give one a competitive edge in the job market. Usually, a person will nd themselves with strengths in about ve to six areas. Sometimes an area where strengths are not present is worth developing. In other cases, competency mapping can indicate nding work that is suited to one's strengths, or nding a department at one's current work where one's strengths or needs as a worker can be exercised. A problem with competency mapping, especially when conducted by an organization is that there may be no room for an individual to work in a eld that would best make use of his or her competencies. If the company does not respond to competency mapping by reorganizing its employees, then it can be of little short term benet and may actually result in greater unhappiness on the part of individual employees. A person identied as needing to learn new things in order to remain happy might nd himself or herself in a position where no new training is ever required. If the employer cannot provide a position for an employee that ts him or her better, competency mapping may be of little use. Challenges and competition are the part of today's society, and therefore, Career Planning is the only task, which can guide us to do what we want to do in our life, rather than just aimlessly changing job 76

all the time in future. Competency Planning is one of the broader aspects of the learning in our existence. We all have some intentions and we all think to have stability in our future lives, and for that purpose, COMPETENCY PLANNING serves as a key to success. Competency Planning helps us to design and formulate our future smoothly. Like, if a person wants to be a banker, then he or she would choose to go ACCA or CA or MBA in nance after completing Intermediate in commerce and Graduation in commerce/business administration. Else he/she would go for CAT course or Masters in commerce or even upto doctorate level. Competency Planning is a life time process we are always learning and growing, and as we do, our interests and needs also change. Career planning is not just making plans to obtain our career, but it also helps us to make many adjustments there will be along the ways we learn throughout our lives. The future is un-predictable, however, we could still make our place in this meritocratic world by making career goals and plans in advance, for getting better opportunities in todayspluralistic and globalize world. We must pre-plan our goals under the supervision of professionals in conscious state of mind, so that we could strategically maintain our goals and follow it towards the path of successful future. 1. The ability to link business and knowledge strategies. 2. The ability to create a basic talent pool and competence networking infrastructure. 3. The ability to create the context for organizational knowledge exchange conversations. 4. The ability to access and use organizational expertise to mitigate risk before engaging in high impact initiatives. 5. The ability to publish & share know-how from day to day business interactions & international best practices. 6. The ability to reect usefully on key organizational outcomes, projects & deliverables insuch a way as to provide earnings for future iterations of the same processes. 7. The ability to create communities of practice to address key strategic themes & validate knowledge assets. 8. The ability to change organizational behavior www.ijsir.co.in


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drivers such as performance management, HR strategy and leadership to support knowledge sharing. 9. The ability to functionally determine knowledge enabling technologies &drive them from a human methodology perspective. COMPETENCY MATRIX The competency Matrix contains24competencies grouped evenly into6 knowledgemapping Dimensions, including self Mastery, Futuring, Sense Making, Design of Intelligent Action, Aligning people to action and Adaptive Learning. The four competencies that reside inside each of the six Dimensions (24 in total) dene a set of related action that, when executed by a leader with intension, create a specic outcome. Each competency is made up of observable skills that can be learned. Like any skill, practice ......and 1 feedback are necessary. Some skills take longer than others to acquire. We view leadership as a lifelong journey.The specic skills represented by these 24 competencies constitute theessentials of leadership. By the essentials we mean those primary skills that can be combined and recombined to handle the majority of challenges faced by leaders today. We have grouped these primary skills into the 24 denable competencies to show function and purpose, choosing dimension names that best describe the groupings of these competencies. Periodically we make adjustments and changes to the skills andcompetencies to reect the evolution of changing demands on leaders. Training Development and Learning Strategies A critical characteristic of successful organizations is a culture of continuous learning and talent development. In today's competitive environment it is crucial to understand that there are many development strategies and evolving technologies that can be leveraged to create this culture. We can provide assistance in helping you design, evaluate and implement these strategies. Technology enabled Learning and Development Today's evolving and emerging technologies such as learning management systems, talent management systems, video sharing and social netwww.ijsir.co.in

working systems can be leveraged and implemented in the continuous learning and talent development process. Subject Matter Experts Our staff has a varied background in both theprivate and public sector. We have SME's that will provide valuableexpertise in designing specic training programs and content for your business. LIMITATIONS While conducting research, at most care was taken to collect data in unprejudiced manner to make this study precise and truthful. But, due to certain unavoidable reasons, there are certain limitations which are as mentioned below. 1. This study engrosses only a part of total number of employees working at Surat manufacturing plant. 2. Research was to be conducted maintaining the decorum of the company. 3. Employees were busy in their work and thus did not spare much time to respond openly to the questions asked. 4. Information and responses given by the respondents may be a biased due to several reasons. 5. Limited time span for carrying out study also restricted the research work. 6. As company is too large, as per their tactics and guiding principle employees were not ready to disclose condential facets. CONCLUSION Hence, with the given research study conducted in this organization, it can be concluded that the concept of competency mapping and Knowledge Management is in between the introduction and growth stage that is it is ahead of introduction stage and has not reached yet to growth stage. It has been also concluded that there is certainly a quest for knowledge in the employees and combining this factor with highly established HR Department and Advanced Information Technology in the organization, competency mapping is need to be regularly carried out here and Knowledge Management will denitely reach to the growth stage in due course of time in this organization. 77


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REFERENCES 1. Abdullah, A. H. (2011). The development of HR practitioner competency model perceived by Malaysian HR practitioners and consultants: a structural equation modeling (SEM) approach. International Journal of Business and Management, 6(11), 240-254. 2. Akanauskiene, I. Bartnikaite, E. (2006), Managerial competence, the attitude of Lithuanian managers, Problems and perspectives in management, Vol. 4 (2). 3. Alan, C. (2008). The strategic role of Human Resource Development in managing core competencies. Human resource development international, 11(2), 183-197. 4. Baloh, P., Desouza, K. C. and Paquette, S. (2011). The concept of knowledge. In: K. C.

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Desouza and S. Paquette (Eds.), Knowledge Management: An Introduction (pp. 35-71). New York: NY: Neal-Schuman Publishers, Inc. 5. Blackler, F. (1995). Knowledge, knowledge work, and organizations: An overview and interpretation. Organisation Studies 16(6), 1021-1046. 6. Bosua, R. and Venkitachalam, K. (2013). Aligning strategies and processes in knowledge management: a framework. Journal of Knowledge Management, 17(3), 331-346, doi: 10.1108/JKM-10-2012-0323 7. Byrne, R. (2001). Employees: Capital or commodity? Career Development International, 6 (6), 324-330.

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CONTROL ANALOGUE ARRIVAL DATA USING DIGITAL VISUAL INFORMATION * Mohit Bajpai Department of Physics , Sai Nath University, Ranchi , Jharkhand , India *Address for correspondence : Mohit Bajpai , Assistant Professor, Department of Physics , Sai Nath University, Ranchi , Jharkhand , India ; Email ID : mohitsky25@gmail.com ABSTRACT Although digital radio signal is more immune to noise than analogue signal, it usually requires large space for storage or wide bandwidth for arrival. With the current feature of network, this makes it impossible for real-time radio communication or arrival. To reduce the requirement of space and bandwidth, radio data need to be compressed to a fraction of its original size before storage or arrival. To achieve good performance of radio compression, one way is to lose some of the relatively unimportant data which is not perceivable by the human visual system. Visual information is playing a more and more important role in our daily life and affects our way of communication and living in many aspects. Digital data and radio applications usually involve storage or arrival of vast amount data. The paper described about vast amount of data. Keywords: Visual Information; Data compression; Radio arrival INTRODUCTION Research of digital image and radio coding are continue back decade and spatial differential pulse code modulation [1, 2] was utilized to encode still. Transform coding techniques were studied in 1970s and the well known block-based discrete cosine transform [3, 4] was proposed [2], motion estimation and compensation techniques were applied to radio coding which provide a significant compression gain over intra-frame coding [5,7] for radio compression. Discrete wavelet transform were also studied since 1980s for data and radio coding and have become the core technology for the still data coding standard. Today, modern data and radio processing techniques have been employed in many fields such as digital television broadcast, surveillance system, medical imaging for disease diagnosis, image/radio based web search, etc. An illustration of a typical digital radio system is given in Figure 1. Usually, the source of a radio is

captured by a camera or a radio recorder in analogue or digital format. For the radio in analogue format, it needs to be converted to digital format before further processing. After digitization, the bit rate produced by the raw radio can be very high. For example, the typical bit rate for a NTSC radio is about 150 Mbps, which is too much for today's typical network bandwidth. Therefore, compression techniques are necessary to be applied to digital radios before they can be further manipulated. Radio compression is the key technology that makes the wide applications of digital radio systems possible. As illustrated in Figure 1, after compression, the radio is converted to the corresponding format that is appropriate for network arrival or storage on hard drives, disks, cassettes, etc. To date, various radio compression techniques have been developed and some of them in more details have been discussed in the paper.

Figure 1: an Example of a digital video system www.ijsir.co.in

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ANALOG CONVERTER As can be seen from Figure 1, a digital radio system usually includes two parts, the encoder and the decoder. The quality of a radio is determined during the process of encoding. When decoding the radio, the decoder reconstructs the radio according to the data in the compressed radio stream which indicates the quality of the radio. A powerful encoder can carry out more smart strategies and complicate algorithms to achieve high radio quality while maintaining good compression ratio. Today, in the existing radio coding standards, a lot of freedom is allowed for the encoding process, that is, the standards do not specify or define the encoding process in a rigid way. This allows tradeoffs between radio compression ratio, frame quality, and encoder's complexity. Depending on different applications, different systems are developed which provide different radio quality. Some systems include only an encoder, such as online radio broadcasting systems, while other systems may have only a decoder, for example a DVD player. For most of the systems, both encoder and decoder are required. A typical example of them is a radio conference system. LITERATURE The compression ratio can be used for indicating the picture quality, since most of the compression techniques operate over a range of compression rate and decompression quality. Generally, the greater the compression ratio, the less the quality of the output images. The trade-off between compression ratio and the quality is an important factor to consider when compressing images. The amount of data is measured in bits, which is the number of binary symbols required to represent the data. The following bitrates are commonly used to represent radio data:  Bits per frame (bpf)  Bits per pixel (bpp)  Bits per second (bps) Reference software In this work, the H.264/AVC reference software codec JM17.2 [2] (referred to as the JM codec), is used as the reference radio codec. The JM codec is commonly used to test new algorithms in the radio coding community. The use of this reference software enables realistic comparison of the 80

performance of different algorithms developed by different researchers. The source code (in the C programming language) for the JM codec can be downloaded . [3] The earlier and the later versions of the JM codec and the revised manual [7] for the H.264 reference software can also be found. [4] The JM encoder reads input parameters from a configuration file. A wide range of encoding parameters can be changed using the configuration file. These include but are not limited to:      

Input radio sequence (concatenated YCrCb 4:2:0 format) Quantisation parameters for I, P and B slices Available MB partition modes I, P and B picture sequence Number of reference frames Rate-distortion optimisation - ON/OFF

The JM codec also provides useful encoding statistics such as bit rate of the encoded bit stream, radio quality in PSNR of luminance and chrominance components of the coded radio and encoding time. For the Scalable and the Multitier extensions similar software has been used [4, 5] both of these are based on the JM software but written in C++. The underlying supposition behind motion estimation is that the patterns corresponding to objects and background in the frame of wave sequence move within the frame to form corresponding objects on the subsequent frame. The idea behind block matching is to divide the current frame into a matrix of macro blocks that are then compared with corresponding block and its adjacent neighbours in the previous frame to create a vector that stipulates the movement of a macro block from one location to another in the previous frame. This movement calculated for all the macro blocks comprising a frame, constitutes the motion estimated in the current frame. In order for the compressed frame to look like the original, the substitute block must be as similar as possible to the one it replaces. Hence a matching criteria or a distortion function is used to quantify the similarity between the target block and candidate blocks. If due to a large search area, many candidates blocks are considered, then the www.ijsir.co.in


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matching criteria will be evaluated many times. Thus the choice of the matching criteria has an impact on the success of the compression. If the matching criterion is slow then the block matching will be slow. If the matching criterion results in bad matches then the quality of the compression will be adversely affected. Fortunately a number of matching criteria are

suitable for use in wave compression. Mean Absolute Error Criteria: The matching criteria mostly used in the literature is minimum mean absolute error, which at point (i, j) for an NxN block and search window of size ±p, is defined as –

Where, −p<= i , j<= +p and c(x,y) and r(x,y) are pixel values at position (x,y) in the current and reference frame respectively. Motion vector is defined as the value of (i, j) for which MAE(i, j) is minimum. Obviously, the residue error between the predicted and actual block in the current frame should be minimum for good matching.

number of such vector components within the defined search area is declared to be the best matching block. Smooth Constrained Mean Absolute Error Criteria: In wave data compression, the residue frame which is calculated by taking the difference of the current and the predicted frame is coded using transform coding technique, called Discrete Cosine Transform (DCT). According to the characteristics of this transform, the number of bits required to code a smooth residue frame will be smaller than the non smooth residue frame. Therefore a smooth constrained based MAE as block matching criteria for motion compensation to reduce the required number of bits for coding besides minimizing the total distortion was proposed. [2] In this method, not only the MAE over the residue block is taken into consideration but also the maximum and minimum residue value error, denoted as MME, is taken care of as well. Since DCT is applied over 8x8 blocks, each residue block (16x16) is divided into four equal size sub blocks (8x8) and MME is calculated for each sub block as

Vector Matching Criteria In MAE based criteria, the average error value is considered while ignoring the individual error term. Proposed vector matching criteria for block matching is to overcome this drawback. In this approach, each NxN block is represented by a vector. Further, each block is subdivided into smaller blocks of size like 2x2, which is represented by a component of the corresponding vector and MAE is calculated between each temporally adjacent sub block in the current and reference frame. A threshold value is chosen by exhaustive search and vector components (out of N2 / 4, assuming the sub block size as 2x2) having value smaller than the threshold value is counted for a given block. Finally, the block having maximum

Where alpha is a weighing factor. The block which has minimum SC-MAE value in the search area, is declared as the best matched block. PROPOSED SCALED VALUE CRITERION Though VMC and SC-MAE based methods have partially reduced the drawbacks of MAE criterion, but they are not suitable for input wave data especially with rotation and zoom effect. Further, the similarity measurement of blocks in VMC is dependent on the input threshold value. In this www.ijsir.co.in

section, a new criterion for block matching is being proposed which not only removes all the shortfalls of MAE but also gives better results than VMC and SC-MAE based techniques. Let R and C are two frames of equal size (NxN) in the reference frame and current frame respectively. Further, let R = 81


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be the pixel values in these blocks. Since the image block may have different range of pixel values along each dimension, the pixel values are redefined on the basis of the higher range of intensities in the frame. If the minimum and

maximum intensity values in reference block R are Rmin and Rmax, and same for the current block are Cmin and Cmax , then the new intensity values of the reference block Rnew and current block Cnew are defined as given below:

This gives new rescaled intensity values for all the pixels. The matching function M(R,C) between block R and block C, is defined as -

The function f(|(Rnew)-(Cnew)|,T) measures the degree of matching between Rnew and Cnew and the positive threshold parameter T= max((Cmax-Cmin) , (Rmax-Rmin)), determines the selection of pixels for matching purposes, i.e. for a value of T only those pixels will contribute in matching for whom |(Rnew) - (Cnew)| T. Finally, the location of any such block R in the reference frame in a given search window for which the value of M(R, C) is minimum, gives motion vector. REFERENCES 1. T. Koga, K. Iinuma, A. Hirano, Y. Iijima, and T. Ishiguro . Motion compensated inter frame coding for video conferencing; in Proc. Nat. Telecommun. Conf., New Orleans, LA, 1981, pp.G5.3.1-G5.3.5. 2. J. Jain and A. Jain, Displacement measurement and its application in inter frame image coding, Communications , IEEE Transactions on, vol. 29, pp. 1799-1808, 1981. 3. L. Reoxiang, Z. Bing, and M. L. Liou, A new three-step search algorithm for block motion estimation. Circuits and Systems for Video 82

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Technology, IEEE Transactions on, vol. 4, pp. 438-442, 1994. M . H . C h a n , Y. B . Yu , a n d A . G . Constantinides, Variable size block matching motion compensation with applications to video coding Communications, Speech and Vision, IEEE Proceedings I, vol. 137, pp. 205212, 1990. G. R. Martin, R. A. Packwood, and I. Rhee, Variable size block matching motion estimation with minimal error, in Proceedings of S P I E, Digital Video Compression: Algorithms and Technologies 1996, pp. 324333. J. A. Robinson, A. Druet, and N. Gosset, Video compression with binary tree recursive motion estimation and binary tree residue coding; Image Processing, IEEE Transactions, vol. 9, pp. 1288-1292, 2000. C. E. Shannon. A Mathematical Theory of Communication Bell System Technical Journal, vol. 27, pp. 379-423,623- 656, Jul., Oct. 1948.

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SECURITY FOR DEVELOPMENT OF GPS EDUCATIONAL SYSTEM *Madhulata Nirmal Department of Computer Science, Naraina College of Engineering &Technology, Kanpur, Uttar Pradesh, India *Address for correspondence: Dr. Madhulata Nirmal, Associate Professor, Department of Computer Science, Naraina College of Engineering &Technology, Kanpur,Uttar Pradesh, India ; E mail ID : madhusgi@gmail.com ABSTRACT Now days, the whole word feels insecure; the environment knows no peace and the people can’t sleep with even one of their eyes closed. These are apparently evidenced in incessant wars between nations that have resulted in genocide and carnage while extent of damages, “Crimes against Humanity"being perpetrated by man against fellow man who has wrecked on lives and properties cannot be quantified. The sounds of guns, Weapons of Mass Destruction (WMD) and Bomb blasts have enveloped the entire world. This paper explores how to secure the GPS educational system using crypto concept by which the secure education can extended in the whole world for human developments. Keywords: GPS; Educational System; Kit; INTRODUCTION The well-known Global Positioning System (GPS) is a satellite-based location system made up of a network of 24 satellites placed into orbit by the U.S. Department of Defense. In these days, GPS has various applications on land, at sea and in the air. Basically, GPS is usable everywhere except where it is impossible to receive the signal such as inside most buildings, in caves and other subterranean locations, and underwater.[1-3] The most famous application is vehicle navigation system with which many cars are equipped. Many knows GPS by name, however, they often does not know the principle of it. Therefore it is necessary to develop an educational system to educate basic principles of GPS. In this paper, an educational system is developed to educate basic principles of GPS. The system is composed of a kit and a monitoring program. The kit is composed of a GPS antenna and a board which contains a GPS receiver. It receives GPS signal through the antenna and transmit to computer through serial cable. The program, developed with MFC using Visual Studio v.6.0[4], has many functions such as (1) receiving and displaying GPS signal from the kit, (2) reading and displaying a logged data from a file, (3) displaying www.ijsir.co.in

current position of satellites in view, (4) displaying SNR of each satellite in view by bar graph, (5) showing current user 3-D position, (6) interfacing with ALMAP and creating map showing current user position from ALMAP, and (7) eventually enabling a user to construct his own navigation system. User can be learned through the system: Positioning principle of GPS. NMEA format. Principle of map display. Characteristics of GPS signal such as signal to noise ratio and Dilution of Precision (DOP). GLOBAL POSITIONING SYSTEM The Global Positioning System was developed to highly accurate position, velocity, and time information to an unlimited number of properly equipped users anywhere on the ground, at sea, in the air, out in space. As a universal positioning system, GPS provides several characteristics not found in other existing equipment which will enhance the conduct of mission operations.[5] These include (1) extremely accurate threedimensional 3-D position, velocity, and time (2)

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The well-known Global Positioning System (GPS) is a satellite-based location system made up of a network of 24 satellites placed into orbit by the U.S. Department of Defense. In these days, GPS has various applications on land, at sea and in the air. Basically, GPS is usable everywhere except where it is impossible to receive the signal such as inside most buildings, in caves and other subterranean locations, and underwater.[1-3] The most famous application is vehicle navigation system with which many cars are equipped. Many knows GPS by name, however, they often does not know the principle of it. Therefore it is necessary to develop an educational system to educate basic principles of GPS. In this paper, an educational system is developed to educate basic principles of GPS. The system is composed of a kit and a monitoring program. The kit is composed of a GPS antenna and a board which contains a GPS receiver. It receives GPS signal through the antenna and transmit to computer through serial cable. The program, developed with MFC using Visual Studio v.6.0[4], has many functions such as (1) receiving and displaying GPS signal from the kit, (2) reading and displaying a logged data from a file, (3) displaying current position of satellites in view, (4) displaying SNR of each satellite in view by bar graph, (5) showing current user 3-D position, (6) interfacing with ALMAP and creating map showing current user position from ALMAP, and (7) eventually enabling a user to construct his own navigation system. User can be learned through the system: Positioning principle of GPS. NMEA format. Principle of map display. Characteristics of GPS signal such as signal to noise ratio and Dilution of Precision (DOP). GLOBAL POSITIONING SYSTEM The Global Positioning System was developed to highly accurate position, velocity, and time information to an unlimited number of properly equipped users anywhere on the ground, at sea, in the air, out in space. As a universal positioning system, GPS provides several characteristics not found in other existing equipment which will 84

enhance the conduct of mission operations.[5] These include (1) extremely accurate threedimensional 3-D position, velocity, and time (2) A worldwide common grid easily converted to other local datum's (3) Passive, all-weather operation (4) Real-time and continuous information (5) Survivable in a hostile environment. GPS is a spaced-based radio-positioning and time-transfer system. It comprises three major segments: Space, Control, and User. The Space Segment, when fully operational, will have an Earth-orbiting constellation of 24 satellites in six planes. They will operate in nominally circular 20,200 kilometer altitude orbits inclined at an angle of 55 degrees with a 12hour period. The spacing of satellites in their orbital planes will be arranged such that a minimum of four satellites will be in view everywhere on or near the surface of the Earth at any time. Each satellite is designed to broadcast a pair of L-band radio frequency signals, known as Link1 (L1) and Link2 (L2). The L1 signal carries a precision ranging code and a course/acquisition ranging code, while L2 carries only precision ranging code. Superimposed on these codes are low-rate navigation message data, including satellite clock and ephemeris parameters, satellite signal health data, and Coordinated Universal Time (UTC) synchronization information. The Control Segment includes a Master Control Station along with a number of Monitor Stations and Ground Antennas located around the world. The Monitor Stations use a specialized GPS receiver to passively track all satellites in view. The information from Monitor Stations is processed at the Master Control Station to determine navigation message of each satellite. This updated information is transmitted to the satellites via the Ground Antennas. The User Segment consists of a variety of User Equipment sets, associated support equipment, and other items. The User Equipment sets, passively operating on the L-band RF signals received from the orbiting satellite constellation, can provide position, velocity, and time data to appropriately equipped users with pre-designed

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International Journal of Scientific and Innovative Research 2017; 5(2) : 83 ‐ 90 P‐ISSN 2347‐2189, E‐ ISSN 2347‐4971

accuracies. The GPS User Equipment sets can be integrated with other self-contained navigation systems to provide accurate positioning under the adverse operating and environmental conditions. DEVELOPMENT GPS EDUCATIONAL KIT The details of the developed GPS educational kit are given below. As shown in Figure 1, the developed educational system consists of GPS kit

developed, GPS receiver, AC adapter, USB cable for a power source from computer, and a computer installed MFC development tool (Visual Studio). GPS antenna is connected to the GPS kit and the GPS kit communicates with the computer through a serial port. The AC adapter and/or USB cable are used to supply power to the GPS kit. The USB cable can be used to supply power to the GPS kit from computer if there is no AC power available.

Figure 1 : Composition of the developed GPS educational kit DEVELOPMENT OF EDUCATIONAL SOFTWARE A monitoring program is developed to communicate with the GPS kit to educate basic GPS principles. The developed software has various functions as follows.  Display satellites in view.  Display signal to noise (S/N) ratio for each satellite  Real-time positioning  Navigation with variable speed using prelogged data from a file  Show useful data such as latitude, longitude, altitude, PDOP, HDOP, VDOP and UTC  Show the received data in NMEA format  Use commercial map for navigation

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Security Lemma Cryptography is widely used in networks. It can be applied anywhere in GPS stack, though it is not common at physical level. The level at which cryptography is applied directly affects its transparency to the user, and its purpose. Cryptography, as we will see, is used for much more data than data confidentially. Indeed, none of the above mentioned security services would be possible to offer without cryptography. As mentioned previously, these services rely on a combination of various security mechanisms, most of which rely on cryptography in one or another. Cryptography is also used in complicated protocols that help to achieve different security services, thus called security protocols. These protocols also rely on various cryptographically based mechanisms to achieve the desired result. 85


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Figure2: Search Network using Authentic Key Network using Authentic Key Let A and B's identities IDA and IDB are interpreted as a "contract" to use security only for this session instance and only between A and B. Public key versions of key establishment based on signatures and asymmetric encryption also exist, but we will close with one last public key variant based on a completely different asymmetric key principle called the Hellman algorithm. The Hellman algorithm is based on the discrete logarithm problem in finite groups. A group G is a mathematical object that is closed under an associative multiplication and has inverses for each element in G. The prototypical example of a finite group is the integers under addition modulo a prime number p. The idea is to begin with an element g of a finite group G that has a long period. This means to g111 * g, g2 11 * g and g311 g. Since G is finite, this sequence must eventually repeat. It turns out that g11 gn for some integer n > 1, and gn11e is the group's neutral element. The element e has the property that h< e < h 11 for every element h in G, and n is called the period of g. With such an element it is easy to compute powers of g, but it is hard to compute the logarithm of gk. If g is chosen carefully, no polynomial time algorithm is known that can compute k from gk. This property leads to a very elegant key agreement scheme: ka = ya mod p .........................(1) Where k is the generated key for all session G and 86

p is prime for random search of networks. We can generate other key for b as equation (1) kb = xb mod p.........................(2) If x and y are two public exchange than for output session key x = ga mod p.........................(3) y = gb mod p.........................(4) The session key is then computed as (K, ga gb). In this protocol, a is a random number chosen by A, b is a random number chosen by B, and 0 denotes the all zeros key. Note that A sends ga unprotected across the channel to B. The quantity gab is called the Diffie-Hellman key. Since B knows the random secret b, it can compute (gab)V (ga)b from A's public value ga, and similarly A can compute gab from B's public value gb. This construction poses no risk, because the discrete logarithm problem is intractable, so it is computationally infeasible for an attacker to determine a from ga. Similarly, B may send gb across the channel in the clear, because a third party cannot extract b from gb. B's signature on message 2 prevents forgeries and assures that the response is from B. Since no method is known to compute gab from ga and gb, only A and B will know the Diffie-Hellman key at the end of the protocol. The step K and gab extract all the computational entropy from the Diffie-Hellman key. www.ijsir.co.in


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The construction (K, ga gb, ) computes a session key, which can be split into encryption and message authentication keys as before. Service { Port = XXXX Socket_type = stream Protocol = tcp Wait = no User = root Passenv = PATH Server = /usr/local/bin/cvs Server_args = -f --allow-root=/usr/cvsroot pserver } Main Window

Fig. 2 shows the main window of the developed monitor program. The left-top part of the fig.2 is shown the satellites in view. The green circles denote satellites used to calculate user position and the grey circles denote satellites just tracked. The number in the circle means ID for each satellite. The left bottom part of the fig. 2 shows signal to noise ratio for each satellite, which transmitted from each satellite. The numbers under the bars are the ID number of the satellites, too. The number in the upper side of the bars denotes the signal to noise of the satellites, respectively.

Figure 3 : The developed monitor program The radio buttons, 'File' and 'COM', can be selected to choose mode. Fig. 3 shows each case. If 'File' button is clicked, the system is operating with pre-logged data from a file. A file can be selected if the button captioned '.' is clicked. Various replay speed can be selected through the

list box. If the 'COM' button is clicked, we can select appropriate serial port and baud rate to communicate with the GPS kit. In this mode, the system provides real-time positioning. The received data are logged into a file like figure 4.

Figure 4: Operation mode www.ijsir.co.in

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Map Setting Window One of the outstanding features of the system is that it is independent of special map. It can use any commercial map. It has been a big program to get a map for GPS educational system because digital map is very expensive and format is often confidential. But a technique to use a cheap commercial map is devised in this paper. Figure 5 shows map setting window of the system. The figure shows how the technique is working. First, execute the commercial map like back most map in figure. 5. If we click the 'Map Setting' button in the Main Window, the Map Setting

Window is shown. Click the left button of the mouse on the Map Setting Window and drag on the commercial map to be selected. If the red box is shown like the figure, then release the mouse left button. If we click 'Setting' button for each edge, the longitude and latitude coordinate of the selected map is appeared at the bottom of the Map Setting Window. Type the longitude and latitude coordinate of four edges of the selected map and click the 'Click' button, and the shown map is saved for later use and the saved map automatically displayed if user position is into the boundary of the map.

Figure 5 : Map Setting Window GPS EDUCATIONAL SYSTEM TEST RESULT The developed educational system is verified by various filed navigation test. Fig. 6 shows a 88

navigation result. The developed GPS kit and laptop computer installed educational software are equipped to a vehicle for field test. While the system is working in one mode, the saved map, if www.ijsir.co.in


International Journal of Scientific and Innovative Research 2017; 5(2) : 83 ‐ 90 P‐ISSN 2347‐2189, E‐ ISSN 2347‐4971

Map Setting Window One of the outstanding features of the system is that it is independent of special map. It can use any commercial map. It has been a big program to get a map for GPS educational system because digital map is very expensive and format is often confidential. But a technique to use a cheap commercial map is devised in this paper. Figure 5 shows map setting window of the system. The figure shows how the technique is working. First, execute the commercial map like back most map in figure. 5. If we click the 'Map Setting' button in the Main Window, the Map Setting

Window is shown. Click the left button of the mouse on the Map Setting Window and drag on the commercial map to be selected. If the red box is shown like the figure, then release the mouse left button. If we click 'Setting' button for each edge, the longitude and latitude coordinate of the selected map is appeared at the bottom of the Map Setting Window. Type the longitude and latitude coordinate of four edges of the selected map and click the 'Click' button, and the shown map is saved for later use and the saved map automatically displayed if user position is into the boundary of the map.

Figure 5 : Map Setting Window GPS EDUCATIONAL SYSTEM TEST RESULT The developed educational system is verified by various filed navigation test. Fig. 6 shows a navigation result. The developed GPS kit and laptop computer installed educational software are equipped to a vehicle for field test. While the system is working in one mode, the saved map, if it exists, is shown when the 'Map View' button is www.ijsir.co.in

clicked. The red circle denotes present position. If the present position crosses one of the boundaries, another map, if it is already saved, is displayed automatically. In this system, ALMAP, the popular commercial map in KOREA, is used. It costs about 10�20 U S D, therefore, we can compose the educational system economically. 89


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Figure 6: Navigation Test Result CONCLUSIONS A GPS Educational system is developed. The system is composed of a kit and a monitoring program. The kit is composed of a GPS antenna and a board which contains a GPS receiver. It receives GPS signal through the antenna and transmit to computer through serial cable. The program, developed with MFC using Visual Studio [4] has many functions such as (1) receiving and displaying GPS signal from the kit, (2) reading and displaying a logged data from a file,( 3) displaying current position of satellites in view, (4) displaying SNR of each satellite in view by bar graph,( 5) showing current user 3-D position, (6) interfacing with ALMAP and creating map showing current user position from ALMAP, and (7) eventually enabling a user to construct his own navigation system. The developed system can be used to educate GPS basic principles and map coordinate system. Furthermore, it can be used to enable to develop other GPS related H/W and/or S/W applications. If the system is combined to other algorithm, it

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can be used as an algorithm educational trainer. REFERENCES 1. David Wells, "Guide To GPS Positioning", Canadian GPS Associates, 1996 2. Fang, B.T, The Minimum for Geometric Dilution of Precision in Global Positioning System Navigation. A I A A Journal of Guidance and Control, Vol. 10, No. 1, pp116, 1987. 3. Parkinson, Global Positioning System: Theory and Application, Vol.. I II, AIAA, 1996.Charles Petzold, "Programming Windows Fifth Edition" , Microsoft Press, 1999. 5. GPS NAVASTAR User's Overview, ARINC Research Corporation, March 1991. 4. Chang-Wan Jeon and Gerard Lachapelle, “A New TLS-Based Sequential Algorithm to Identify Two Failed Satellites”, International Journal of Control, Automation, and Systems, Vol. 3, No. 2, pp. 166-172, June 2005.

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METHOD OF CHILDS LEARNING USING CARTOONS AND NASQL *Madhulata Nirmal Department of Computer Science, Naraina College of Engineering &Technology, Kanpur, Uttar Pradesh, India Address for correspondence: Dr.Madhulata Nirmal,Assistant Professor, Department of Computer Science, Naraina College of Engineering & Technology, Kanpur, Uttar Pradesh, India; E mail ID : madhusgi@gmail.com ABSTRACT The admission system and reservation system and other public relation system are working publically. But very few system in our country are made for children who are going to be tomorrow's professional. The creativity in a child mind always needs to be encouraged so that he/she can be a good thinker tomorrow. And as children are always mesmerized by their comic heroes and if the concept of creativity is imbibed in relation to these heroes it will further stimulate creativity to a newer height and enhance children imagination, the need is felt to develop this program.The purpose of the paper aims at this, to enhance the creativity in child mind this is basically a computerized cartoon and comics program which children can enjoy and also maneuver to a certain extent. Keywords: Computerize cartoon; Comics program; Automatic system; Data base cartoons; INTRODUCTION Violence in cartoons is an integral part of cartoon content. In fact, frequency of violence in cartoons is higher than in live-action dramas or comedies.[1] As a consequence, youth are more likely to view media-depicted violence during Saturday morning cartoons than during prime-time [2] television hours (8:00–11:00 PM. However, there are qualitative differences between the acts of violencedepicted during live-action dramas and those depicted in cartoons. Cartoon violence meant for a youthful audience (asopposed to animated films for adults, such as Heavy Metal) tend to involve minor acts of violence: realisticallyportrayed death is rarely shown and graphic acts of violence are seldom televised. Additionally, cartoons sanitize theoutcomes of violence, in that it is unusual to see the victims suffering in a life-like manner. In contrast, liveactiondramas airing during prime-time regularly involve major acts of violence (e.g., rape and murder), and the pain and suffering of the victim is [3] often highlighted. Although many violent cartoons meant for youthful consumption contain comedic elements (e.g., Woody Wood-pecker, Scooby Doo), some of these cartoons just portray the violence. For www.ijsir.co.in

instance, Samurai Jack, X-Men Evolution,and Batman: The Animated Series depict animated violence, with little to no comedic elements. Moreover, for these types of animated shows, violence is found at the beginning and end of disputes. Presence or absence of comedy during violence is an important consideration when evaluating the effects of viewing cartoons on youth, for there isboth theory and research to support the contention that comedic elements may [4] camouflage and trivialize depictions ofviolence. LITERATURE If one accepts the research that children come to media in search of stimulating and interesting stories, then the realm of myth has much to offer us in understanding children's viewing and play choices with old and new media. In myth, we capture the long-held values and beliefs about what is important to us. The collective unconscious and the archetypes building on psychoanalytic [5] Theory, created the idea of the collective unconscious, the repository of the shared collective images of the human species. Within the collectiveunconscious, we have inherited the 91


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archetypes, prototypical images that are passed onanew to each new generation. These images, according toFunketal[6],exist in the collective unconscious as primitive images that are then developed by ourindividual and cultural experiences. These archetypes include the persona (our externalpresentation of self to the world), the anima (the feminine side of the male psyche) andanimus (the masculine side of the female psyche), the shadow (the life-preserving, yetpotentially destructive facet of the personality), the self, the wizard, the hero, the crone, animals such as wolves howling, symbols of nature such as the full moon, and religious [7] symbols such as birth and rebirth. Of particular interest to ourdiscussion are those archetypes most closely associated with aggression: the hero andthe shadow.[8]In mythic tales that existed long before the appearance of a movie or televisionscreen, the hero pursued a quest, faced obstacles, and eventually triumphed over themto be reborn as a new and more fully integrated person . [9] The travelsof Odysseus after the Trojan War are one such quest, eventually resulting in his returnto his homeland. But even there,Odysseus had to fight to regain his wife from those who thought him dead and who had pursued Penelope as their own wife. The trial ofstringing his own bow and shooting an arrow straight through the sockets of twelve axheads in a row, a task that had kept his wife's many suitors at bay, led to victory overhis enemies and the restoration of his home and family. The heroic formula, built uponmyths

such as these, continues to appear in our culture as movie after movie andprogram after program reenact the personal struggles and triumphs that we all face inlife. As these types of stories and myths are universal themes, children can relate tothese tales.[10] In the hero's tale, there is also a dark force, the villain. It is that villain, or inJung's conception the dark side of the shadow, that provides the countervailing force ofthe hero. So the white knight fights against dark evil forces. In fiction,particularly children's television programs, the lines of good and evil are clearly marked.The good guys are good; the bad guys are evil. These plot lines simplify the plotcomprehension skills that children must acquire to get the message. In adult programs, however, frequent commercial interruptions, particularly between the violent action and consequences, can impede children's understanding that the villain is punished for his dark deeds. METHOD AND IMPACT OF DATA BASE In the original Galton system of classification, there are three basic cartoons patterns: loop (60–65%), whorl (30–35%), and arch (5%). From this basic model, we get more sub classifications for plain arches or tented arches, and into loops that may be radial or lunar, depending on the side of the hand toward which the tail points. Lunar loops start on the pinky-side of the finger, the side closer to the ulna, the lower arm bone. Radial loops start on the child-side of the cartoon, the side closer to the radius.

Figure1: Use of data base in Child Cartoons 92

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SELECT dept_name, CAST(NULL AS CHAR (10) AS job_title, COUNT(*) FROM Personnel GROUP BY dept_name UNION ALL SELECT CAST (NULL AS CHAR(8)) AS dept_name, job_title, COUNT(*) FROM Personnel GROUP BY job_title; which can be rewritten as: SELECT dept_name, job_title, COUNT(*) FROM Personnel GROUP BY GROUPING SET

(dept_name, job_title); SELECT CASE GROUPING (dept_ name) WHEN 1 THEN 'department total' ELSE dept_name E N D A S dept_name, C A S E GROUPING (job_title) WHEN 1 THEN 'job total' ELSE job_title_name END AS job_title FROM Personnel GROUP BY GROUPING SETS (dept_name, job_title);

Figure2: Relation between child mind and cartoons structure using data query Whorls may also have subgroup classifications including plain whorls, accidental whorls, In the original Galton system of classification, there are three basic fingerprint patterns: loop (60–65%), whorl (30–35%), and arch (5%). From this basic model, we get more sub classifications for plain arches or tented arches, and into loops that may be radial or lunar, depending on the side of the hand toward which the tail points. Lunar loops start on the pinky-side of the finger, the side closer to the ulna, the lower arm bone. Radial loops start on the thumb-side of the finger, the side closer to the radius. Whorls may also have subgroup classifications including plain whorls, accidental whorls. CONCLUSION With the growth in demand globally for out sourced animation services for child entertainment, the opportunity for world animation providers remains high. The Indian animation industry remains a strong player in the sector because of its established reputation for quality work and its inherent and creative talent pool. However, if the Indian animation industry remains static in the short term, its share in the www.ijsir.co.in

global animation market will be easily captured by regional competitors who are accelerating development at a pace faster than India. Most notably, competitors are quickly addressing infrastructure, evolving client requirements and preferences and aligning industry capacity to meet current market demands. REFERENCES 1. Aluja-Fabregat, A., &Torrubia-Beltri, R. (1998). Viewing of mass media violence, perception of violence, personality, and academic achievement. Personality and Individual Differences, 25, 973−989. 2. Atkin, C. (1983). Effects of realistic TV violence vs. fictional violence on aggression. Journalism Quarterly, 60, 615−621. 3. Bandura, A. (1965). Influence of models' reinforcement contingencies on the acquisition of imitative responses. Journal of Personality and SocialPsychology, 1, 589− 595. 4. Bandura, A., Ross, D., & Ross, S. A. (1963). Imitation of film-mediated aggressive models. Journal of Abnormal and Social Psychology, 66(1),3−11. 93


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5. Gailey, C.W. (1996). Mediated messages:

8. Hall, C. &Nordby, V. (1973). A primer of

Gender, class, and cosmos in homevideo games. In I.E. Sigel (Series Ed.) & P.M. Greenfield & R.R. Cocking (Vol. Eds.), interacting with video: Vol. 11. Advances in applied developmental psychology (pp. 9-23). Norwood, NJ: Ablex. 6. Funk, J.B., Germann, J.N., & Buchman, D.D. (1997). Children and electronic games in the United States. Trends in Communication, 2, 111-126. 7. Funk, J. B. (2002). Children and violent video games: Strategies for identifying high risk players. In D. Ravitch, & J. Viteritti (Eds), Children and the Popular Culture. Johns Hopkins University Press.

Jungian psychology. New York: Mentor Books. 9. Handford, H. A., Mayes, S. D., Matson, R. E., Humphrey, F. J., II, Bagnato, S., Bixlex E. O., & Kales, J. D. (1986) Child and parent reaction to the Three Mile Island nuclear accident. Journal of the American Academy of Child Psychiatry, 25, 346-56. 10. Huston-Stein, A., Fox, S., Greer, D., Watkins, B.A. & Whitaker, J (1981). The effects of TV action and violence on children's social behavior. The Journal of Genetic Psychology, 138, 183-1991.

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STEADY STATE THERMAL ANALYSIS OF DISC BRAKE ROTOR GRAY CAST IRON F12801 1

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* Hredey Mishra , Vikas Mishra 1 Research scholar, Sai Nath University, Ranchi, Jharkhand , India , 2Professor, Department of Mechanical Engineering, Geetanjali University Udaipur, Rajasthan , India * Address for correspondence : Hredey Mishra, Research scholar, Sai Nath University, Ranchi, Jharkhand, India ; Email ID : hredeyamishra@gmail.com ABSTRACT Now a day in field of automotive very wide range of innovation happens regarding high speed vehicle, to better control of these high speed vehicles the most important factor is braking system. So in this research study we found the better option to improve the quality of the disk brakes for their characteristics of braking stability, and changing of torque in very high speed like formula one car racing events . In the disc brake rotor assembly, disc rotor is very important component so that we optimize the heat transfer rate in the rotor due to frictional heat generated on the interface of rotor, which leads to undesirable effects such as brake fade phenomena, local scoring, thermal cracking and thermo elastic instability. In the course of braking the parameters of the processes like load, temperature and conditions of contact vary with time so that we consider the effects of moving heat source with relative sliding speed variation. A steady-state thermal analysis is performed for four seconds of braking duration to characterize the temperature fields of the solid rotor with appropriate thermal boundary conditions. For the present analysis of solid rotor, CREO-PRAMETRIC 1.0 is used for the CAD modelling of the rotor and ANSYS14.0 is used as a FEA tool. Once the brake rotor temperature release in time duration than the distribution of temperature is obtained a transient structural analysis is performed to predict the failure of the disk rotor. Keywords: Disc brake; Steady-state; Frictional heat; Analysis; Rotor; Creo- parametric; FEM INTRODUCTION These days technology improved rapidly day to day which changes in vehicle sector surprisingly. On comparison of vehicle production before 20-25 years ago and later, we find abundant difference in aspect of comfort, economy and function and particularly in Safety. Very careful attention is given these days to passive and active safety system for vehicle. Active safety means helpful in avoiding traffic event and passive safety system protect passengers and drivers against injuries in traffic. In braking system one of most important is active safety of vehicle. Hence Braking system is necessary in an automobile for stopping the vehicle. Brakes are applied on the wheels to stop or to slow down the vehicle. Brakes should also be consistent with safety. While braking, most of the kinetic energy is converted into thermal energy which increases the disc temperature. This study deals in disc rotor design, disc rotor www.ijsir.co.in

profile selection, disc rotor material selection and thermal stress analysis on Honda CB Unicorn, 150cc brake disc rotor. The heat dissipated along the brake disc surface during the periodic braking via conduction, convection and radiation. The findings of this research study provide a useful design tool to improve the brake performance of disc brake system. The steady-state theory is a view that the universe is always expanding but maintaining a constant average density, matter being continuously created to form new stars and galaxies at the same rate that old ones become unobservable as a consequence of their increasing distance and velocity of recession. A steady-state universe has no beginning or end in time; and from any point within it the view on the grand scale, the average density and arrangement of galaxies--is the same. Galaxies of all possible ages are intermingled. The theory was first put forward by Sir Gold. It was further 95


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flow rates, and heat fluxes in an object that are caused by thermal loads that do not vary over time. Such loads include the following:  Convections  Radiation  Heat flow rates  Heat fluxes (heat flow per unit area)  Heat generation rates (heat flow per unit volume)  Constant temperature boundaries.

developed by Sir Fred Hoyle to deal with problems that had arisen in connection with the alternative big-bang hypothesis. Observations since the 1950s have produced much evidence contradictory to the steady-state picture and supportive of the big-bang model. The ANSYS /Multiphysics, ANSYS/Mechanical, ANSYS /FLOTRAN, and ANSYS/Thermal products support steady-state thermal analysis. A steadystate thermal analysis calculates the effects of steady thermal loads on a system or component. Engineer/analysts often perform a steady-state analysis before doing a transient thermal analysis, to help establish initial conditions. A steady-state analysis also can be the last step of a transient thermal analysis; performed after all transient effects have diminished. We can use steady-state thermal analysis to determine temperatures, thermal gradients, heat

DESIGN OF ROTOR CAD model of disc brake rotor was done in CREO-Parametric dimensions of rotor mentioned in Table 1. Material used is Gray Cast Iron (F12801) because it is relatively hard and resist wear, cheaper than steel, it absorbs and dissipates heat as well.

Table1: Material properties (F12801) Properties

Disc

Mass density(kg/m3)

7500

o

Specific heat (J/k c)

490 o

Thermal conductivity (w/m c)

46

Inner radius (mm)

150

Outer radius (mm)

320

Disc thickness (mm) (Total)

21 (7+7+7)

Table 2 : Alloy composition

96

Iron(Fe)

92.1-93.9

Carbon(C)

3.1-3.4

Silicon (Si)

2.5-2.8

Manganese (Mn)

0.05-0.07

Phosphorus (P)

0-0.9

Sulfur (S)

0-0.15

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Fig. 1 : CAD model of Rotor in Creo-Parametric After the part modelling of disc rotor we save this part as a copy in .igs file format for

the further analysis of the disc brake roto in Ansys 14.0.

Fig. 2 : Imported model of rotor in Ansys workbench BOUNDARY CONDITION FOR THE STEADY STATE ANALYSIS After importing the cad model in Ansys workbench have meshed the rotor in suitable www.ijsir.co.in

elements to good result of the analysis. 97


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Fig.3 : Meshed model of the rotor GEOMETRICAL PROPERTIES OF THE MODEL The geometrical properties of the model for the meshing are shown in the table 3 Table 3 : Geometrical Properties of rotor Type

Definition Design Modeller

Length Unit

Millimetres

Element Control

Program Controlled

Display Style

Body Colour

Length X

Bounding Box 320. mm

Length Y

320. mm

Length Z

46. mm Properties

Volume

1.1251e+006 mm³

Mass

6. kg

Scale Factor Value

1. Statistics

98

Bodies

1

Active Bodies

1

Nodes

183818

Elements

109734

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Boundary condition for the analysis: - For the boundary condition the initial temperature set 22 oC shown if fig-4 at A and the convection

set at 22 0 C with the convection coefficient 1.24 10^-06. The detailed of boundary condition is shown in fig-4.

Fig. 4 : Boundary condition for the analysis ANALYSIS OF ROTOR Steady State thermal analysis- After application of appropriate thermal boundary conditions the initial temperature analysis is shown in the fig-5. From this analysis this clarifies that the outer area of the rotor produces maximum 80 0

C temperature and inner area of the rotor produces minimum 78.542 0C temperature which are low from the melting temperature of the material F12801 (1180 o C). So the material is safe for this analysis of initial temperature.

Fig.5 : Initial temperature analysis

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Fig. 6 : Final temperature analysis

The result of this analysis indicates that the temperature flows from the inner side of the rotor hub to the outer side. It means high temperature

is in the inner side of the rotor hub and the low temperature at the outer side of the rotor hub as shown in fig.6

Fig.7: Analysis for the directional heat flux From the direction heat flux analysis we found plastic deformation of the rotor during the the information regarding the heat flux braking as shown in fig.7. intensity on the rotor and the rotor hub to avoid The total heat flux analysis shows the information for the combine effect heat flux in rotor area shown in fig.8 100

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Fig. 8 : Analysis for total heat flux Graph between temrature and covection cefficient:- This graph shows the relationship of the increment of the temprature and the effect of the covection coefficient of the material

indicating that if the temprature increases the coefficient also increases but in the parabolic form.

Fig. 9 : Graph between temrature and covection cefficient www.ijsir.co.in

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Graph of increating temprature in radial direction- This graph shows the increament of the temperatures in ratial direction. From

the graph, it is shown that the themprature flows inner to outer direction with low to high.

Fig. 10 : Graph of increating temprature in radial direction RESULTS AND DISCUSSION From the steady state analysis of the disc rotor it was found that the material F12801 gives the better result from the convection cast iron in the

initial result and the non-reality effect is also safe for this material. The results of the steady state analysis are shown in bellow table 4.

Table 4 : Results of Steady State thermal analysis of the disc rotor Analysis Method

Temperature (oC)

Total Heat Flux(W/mm2)

Direc onal Heat Flux(W/mm2)

Temperature 2 (oC)

FEM (Ansys)

22

3.3 * 10^-3 to 5.33 *10^-9

2.14*10^-3 to 2.11*10^-3

80

CONCLUSION This analysis can provide the useful information regarding the further analysis of the disc rotor to use the rotor to more and more complex condition for the braking condition and the nonlinearity of the rotor to provide the more stability in the field of 102

the braking system. The future scope for this study may be in transient thermal analysis, modal analysis transient structural analysis of the disc to collect the more information and feasibility of the rotor in various condition of the braking system. www.ijsir.co.in


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REFERENCES 1. M. T. V and D. S. P. M, Structural and Thermal Analysis of Rotor Disc of Disc Brake, International Journal of Innovative Research in Science, Engineering and Technology, vol. 2, no. 12, pp. 7741-7749, 20138. 2. B. N and P. G, Design and Analysis of Disc B r a k e R o t o r f o r a Tw o w h e e l e r, International Journal of Mechanical and Industrial Technology, vol. 1, no. 1, pp. 712, 2014. 3. B. M. Belhocine A, Temperature and Thermal Stresses of Vehicles Gray Cast Brake, Journal of Applied Research and Technology, vol. 11, pp. 675-682, 2013. 4. D. Swapnil R. Abhang, Design and Analysis of Disc Brake, International Journal of Engineering Trends and Technology, vol. 8, pp. 165-, 2014. 5. P. P. C. D. S. B. Jaju, A Review on Thermal and contact stress analysis of Disc braking

www.ijsir.co.in

6. 7.

8.

9.

system, International Journal of Engineering Research and General Science, vol. 2, no. 1, pp. 78-84, 2014. Halderman J.D , Automotive Brake Systems, Prentice Hall, Inc, NJ, USA, 1996. Praveena S, Lava Kumar M, Kesavulu A , Modeling and Thermal Analysis of Disc Brake Praveena S. Int. Journal of Engineering Research and Applications Vol. 4, Issue 10(Part- 3), October 2014. Venkatramanan R, Kumaragurubaran SB, Vishnu Kumar C, Sivakumar S,Saravanan B. Design and Analysis of Disc Brake Rotor. International Journal of Applied Engineering Research ,Volume 10, Number 19 (2015) Baskara Sethupathi P, Muthuvel A, Prakash N., Stanly Wilson Louis , Numerical Analysis of a Rotor Disc for Optimization of the Disc Materials. Journal of Mechanical Engineering and Automation 2015.

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TRANSIENT THERMAL ANALYSIS OF DISC BRAKE 105 - 113 ROTOR GRAY CAST IRON F12801 Hredey Mishra1, Vikas Mishra2 1

2

Research scholar, Sai Nath University, Ranchi, Jharkhand , India , Professor, Department of Mechanical Engineering, Geetanjali University Udaipur, Rajasthan , India * Address for correspondence: Hredey Mishra, Research scholar, Sai Nath University, Ranchi, Jharkhand, India ; Email ID : hredeyamishra@gmail.com ABSTRACT

Transient analysis is most important to collect the information about nonlinear behaviour of the component or product. In the present the study, we collected different response for the loading condition on disc rotor and its stability in critical condition. The transient simulation calculates the response on arbitrary excitations. Substantial for the transient analysis is the consideration of energy storing in the components. In the study, we saw the transient behaviour in thermal condition as well as in structural condition. From CREO-Parametric for the CAD modelling of the disc rotor and Ansys 14.0 workbench for transient analysis of the disc rotor, from the thermal transient analysis we get the information regarding heat flux, heat formation during braking, heat dispassion through the convection and from the structural transient analysis we got the information regarding mechanical deformation and some mechanical behaviour of the rotor Keywords: Disc rotor; Transient; Response; Structural; Analysis; CREO-parametric; Ansys workbench INTRODUCTION A transient analysis, by definition, involves loads that are a function of time. In the Mechanical application, we can perform a transient analysis on either a flexible structure or a rigid assembly. For a flexible structure, the Mechanical application can use the ANSYS Mechanical APDL, Samcef or ABAQUS solver to solve a Transient Structural analysis. We can perform a transient structural analysis (also called timehistory analysis) in the Mechanical application using the transient structural analysis that specifically uses the ANSYS Mechanical APDL solver. This type of analysis is used to determine the dynamic response of a structure under the action of any general time-dependent loads. We can use it to determine the time-varying displacements, strains, stresses, and forces in a structure as it responds to any transient loads. The time scale of the loading is such that the inertia or damping effects are considered to be important. If the inertia and damping effects are not important, we might be able to use a static analysis instead. A transient structural analysis can be either linear or nonlinear. All types of nonlinearities are 104

allowed - large deformations, plasticity, contact, hyper elasticity, and so on. ANSYS Workbench offers an additional solution method of ModeSuperposition to perform linear transient structural analysis. In the Mode-Superposition method, the transient response to a given loading condition is obtained by calculating the necessary linear combinations of the eigenvectors obtained in a modal analysis. Transient Structural Analysis Using Linked Modal Analysis System is more useful. The Mode Superposition method is not available to the Samcef or ABAQUS solver. The ANSYS/Multiphysics, ANSYS/Mechanical, ANSYS/FLOTRAN, and ANSYS/Thermal products support steady-state thermal analysis. A steady-state thermal analysis calculates the effects of steady thermal loads on a system or component. Engineer/analysts often perform a steady-state analysis before doing a transient thermal analysis, to help establish initial conditions. A steady-state analysis also can be the last step of a transient thermal analysis; performed after all transient effects have diminished. From the transient analysis of the rotor we clearly able to understand www.ijsir.co.in


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following information about the disc rotor 1. Understand how nonlinearities (if you are including them) affect the structure's response by doing a static analysis first. In some cases, nonlinearities need not be included in the dynamic analysis. Including nonlinear effects can be expensive in terms of solution time. 2. Understand the thermal deformation in the rotor during the high temperature produced while braking. And information regarding heat input and heat releases for the better stability of the brake rotor.

3. Analyse a simpler model rotor which can provide good insight into the problem at minimal cost. This simpler model may be all you need to determine the dynamic response of the structure. MECHANICAL AND THERMAL PROPERTIES OF THE MATERIAL F12801

Table1 contains the mechanical properties of the material and table 2 contains the thermal properties of the material

Table-1 Mechanical properties of (F12801)

Properties

Quantity

Brinell Hardness

230

Compressive(crushing) strength (MPa) Young’s modulus

970 180

(Gpa)

Elongation at break

.52%

Fatigue strength (MPa)

130

Pission’s Ratio

0.29

Shear modulus(GPa)

69

Shear Strength (MPa)

390

Tensile strength : Ultimate (UTS) (MPa)

310

Tensile strength :yield (proof) (MPa)

200

Table 2: Thermal properties of (F12801)

Properties

Quantity

Melting completion (o C)

1380

Melting completion ( o C)

1180

Specific heat capacity (J/kg-K)

490

Thermal Conductivity W/m-K

46

Thermal expansion (μm/m

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-

K)

11

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Table-3 Unclassified Properties of F1201

Properties

Quantity

Density (g/cm3)

7.5

Embodied carbon kg (CO2/kg)

1.5

Embodied energy (MJ/kg)

21

Embodied Water

44 Table : 4 Alloy Composition

Percentage of composition

Alloys

Iron(Fe)

92.1-93.9

Carbon(C)

3.1-3.4

Silicon (Si)

2.5-2.8

Manganese (Mn)

0.05-0.07

Phosphorus (P)

0-0.9

Sulfur (S)

0-0.15

Table-3 shows the unclassified properties of the material and table- 4 shows the alloys composition of the material. These alloys composition give the material suitable compressive strength and hardness for braking application. CAD MODELLING OF DISC ROTOR For the CAD modelling CREO-Parametric 1.0 is used, rotor model made in part modelling

section of CREO-Parametric after that model save “.igs” file format for importing in ANSYS for further analysis of the component. Figure 1 shows the wireframe model of the disc rotor and figure 2 shows the solid part model of the rotor which is used in transient thermal analysis and figure 3 shows the assembly of block A and block and rotor for transient structural analysis of the rotor.

Fig1: Wireframe model of the disc rotor 106

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Fig 2 : Solid Part model of the disc rotor TRANSIENT THERMAL ANALYSIS IN ANSYS WORKBENCH The ANSYS/Multiphysics, ANSYS/Mechanical, ANSYS/Thermal, and ANSYS/FLOTRAN products support transient thermal analysis. Tr a n s i e n t t h e r m a l a n a l y s i s d e t e r m i n e s temperatures and other thermal quantities that vary over time. Engineers commonly use temperatures that a transient thermal analysis calculates as input to structural analyses for thermal stress evaluations. Many heat transfer applications-heat treatment problems, nozzles, engine blocks, piping systems, pressure vessels, etc. involve transient thermal analyses.

A transient thermal analysis follows basically the same procedures as a steady-state thermal analysis. The main difference is that most applied loads in a transient analysis are functions of time. To specify time-dependent loads, we first divide the load-versus-time curve into load steps. Each "corner" on the load-time curve can be one load step, as shown in the following sketches. For the transient thermal analysis of the rotor disc first of all the imports the CAD model of the rotor from CREO-Parametric which save as ".igs" file format. Figure-3 shows the imported model of the disc rotor.

Fig .3 : Imported model of rotor www.ijsir.co.in

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After import the rotor model in Ansys workbench we go for the meshing of the model in suitable number of elements with specific size for better

result. Figure- 4 shows the meshed model of the rotor

Fig4 : Meshed model of rotor From the meshed model of the rotor we see that the number of node I the components are 75831 and the number of elements are 42318.

Boundary condition for the analysis is shown in figure-5

Fig. 5 : Boundary condition for transient thermal analysis of rotor 108

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Fig .6 : Result of Appling initial temperature and final temperature in rotor

Fig. 7: Result of Appling heat flux in rotor The figure-6 and figure-7 show the result for the transient thermal analysis for the application of initial temperature 22 0C and final temperature 1000 0C and heat flux result for the convection of the heat.

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Table 5: Effect of temperature increment on convection coefficient. shows the result for change in convection coefficient variation thought the temperature increment in rotor

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Temperature [ 0C ]

Convection Coefficient [W/mm²·°C]

1

1.24e-006

10

2.67e-006

100

5.76e-006

200

7.25e-006

300

8.3e-006

500

9.84e-006

700

1.101e-005

1000

1.24e-005

Figure- 8 shows the application of the braking system through the time and its respective

temperature increment

Fig. 8 : Effect of temperature in time difference Figure-8 shows the two graphs between time (sec) and temperature (0C) red curve and the green curve. The red curve shows the maximum global condition and green curve shows the 110

minimum global condition. Figure 9 shows the changes in heat flux in time duration for both maximum global condition (red curve) and minimum global (green curve). www.ijsir.co.in


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Fig .9 : Effect of total heat flux in time difference RESULTS AND DISCUSSION For the input data of the material thermal conductivity 46 4.6e-002 W mm^-1 C^-1 and specific heat 4.9e+005 MJ kg^-1 C^-1, the results show that during the time difference the convection coefficient and total heat flux increase if the time of braking is more so in the place of continuous apply the brake, it is applied in rapid to minimise the effect of the temperature on the rotor. CONCLUSION The transient thermal analysis of the disc rotor states that if the time of applying brake force is increased it means the duration of the contact time of the rotor and the pad then more heat will be produced and the probability of the plastic deformation also increases so we have to use that material which convection coefficient increases with the like F12801. The material F12801 is suitable for disc rotor. REFERENCES 1. Artus.S, Cocquempot, www.ijsir.co.in

2.

3.

4.

5.

Hayat. S, Covo.C , (2004) , Temperature Estimation of CHV Brake Discs using an Energy Balance Approach, IEEE Intelligent Tr a n s p o r t a t l o n S y s t e m s C o n f e r e n c e , Washington, D.C., USA,pp390-395. Artus.S, Cocquempot, Staroswiecki .M, Hayat. S, Covo .C,(2005), CHV's brake discs temperature estimation: results in open road Tests, Proceedings of the 8th International IEEE Conference on Intelligent Transportation Systems Vienna, Austria. Daniel Hochlenert, Thira Jearsiripongkul,(2006), Disk Brake Squeal: Modeling and Active Control ,IEEE transactions on RAM. Fei Gao1, Gang Xiao, Yuanming Zhang, (2009), Semi-similarity design of motorcyclehydraulic-disk brake: strategy and Application, pp-576-579. Guangqiang Wu , Lin He ,Xianjie Meng, (2009), Numerical Study on the Vibration Characteristics of Automobile Brake Disk and Pad, IEEE transactions, pp-1798-1802.

Staroswiecki.M, 111


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6. Hyun Cheol Kim , Jungwon Hwang, WhoiYul Kim , Yeul-Min Baek,(2009), Image Analysis System for Measuring the Thickness of Train Brakes, First IEEE Eastern European Conference on the Engineering of Computer Based Systems.pp-83-87. 7. Kyoung Kwan AHN , Tran Hai NAM , (2009), A New Structure of MR Brake with the Waveform Boundary of Rotary Disk, ICROS-SICE International Joint Conference, pp -2997-3002. 8. Li Yuren , Liu Weiguo , Tian Guanglai, Wei Hanbing , Xue Jing, (2009), The Finite Element Model of Transient Temperature Field of Airplane Brake Disks with Rough Surface Profile, Proceedings of the IEEE International Conference on Automation and Logistics.pp-41-44. 9. Liuchen Fan , Yaxu Chu , Xuemei Sun , Xun

112

Yang ,(2010), Thermal-structure coupling analysis of disc brake, International Conference on Computer, Mechatronics, Control and Electronic Engineering (CMCE).pp-406-409. 10. Pramod Kumar.K, Ravikiran Kadoli, Anil Kumar. M.V. (2010) Mechanical and Magnetic Analysis of Magnetostrictive Disc Brake System, 5th International Conference on Industrial and Information Systems, ICIIS 2010. 11. Michael Goldfarb, Ryan J. Farris, (2010), Design of a Multidisc Electromechanical Brake, I E E E / A S M E transactions on mechatronics, pp-1-9. 12. Mugeo Dong, Sok Won Kim, Nam-Ku, Thermo-physical Properties of Automotive Brake Disk Materials, Department of Physics, University of Ulsan pp-680 – 749.

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THE EFFECT OF EXERTION ON HEART RATE AND RATING OF PERCEIVED EXERTION IN INDOLENT FEMALES 1

1

2

Aisha Ansari , Mohammad Shahid Ali , Jagatheesan Alagesan , *Prathap S

1,3

1

Faculty of Medical and Paramedical sciences, Himalayan University, Itanagar, Arunachal Pradesh, India; 2College of health sciences, Gulf Medical University, Ajman,UAE; 3Aarogyam Hospital, Reengas, Sikar,Rajasthan,India *Address for Correspondence: Dr. Prathap S, Aarogyam Hospital, Reengas, Sikar,Rajasthan,India Email ID: bhanwarpunit6@gmail.com ABSTRACT

Physical fitness is defined as "a set of attributes that people have or achieve that relates to ability to perform physical activity". Physically unfit leads to problems like overweight, obesity and other cardiovascular issues. The need of this study to analyze the effect of exercises on heart rate and rate of perceived exertion in indolent females with other cardiorespiratory vitals using a using short bout of exercises in normal healthy females. Healthy females according to BMI aged 20 to 30 years were recruited using convenience methods (N = 50). The results were obtained using t-test. The group was homogenous at the baseline and showed statistically significant changes after intervention with short bout of exercises. Present study indicates that the major vital of cardiorespiratory fitness that is VO2 max was 34.78±3.2 in normal BMI group. Along with this level of perceived exertion was 14±3 among normal BMI group. After the post exercise heart rate, blood pressure and respiratory rate of normal individuals fall in the good range. This study indicates the increased need of physical activity among young females and keeps their BMI under control to avoid any cardiorespiratory complications. Keywords: BMI; Cardiorespiratory fitness; RPE; VO2 max INTRODUCTION Obesity and weight gain are imposing a growing threat to world health, as in many countries 20–30% of adults are categorized as clinically obese, and their number is still increasing (WHO,1999; WHO 2002). Many studies have demonstrated an association of both a high body mass index (BMI) and a sedentary lifestyle with greater risk for cardiovascular disease (Wang and Lobstein, 2006). Physical activity (PA) improves cardiorespiratory fitness and is associated with reduced health outcomes such as cardiovascular disease (Kurth and Schaffrath, 2007). Physical activity has also been shown to lower resting heart rate and lower resting blood pressure (He et al., 2011). Heart function can be described as the various measures of efficiency for the heart and circulatory systems during rest and activity (e.g. resting and exercise HR, resting and exercise BP, resting and exercise FEV1,FVC). And to investigate whether regular exercise was protective against reduced heart rate, or adverse effects of obesity and weight gain on heart rate www.ijsir.co.in

were modified by regular exercise (Haerens et al., 2007). Nonetheless, emerging evidence supports the notion that a lifestyle-modification program characterized by an increase in physical activity and a balanced diet can reduce obesity and the risk of obesity-related comorbid conditions despite minimal or no weight loss. Clinicians could encourage positive lifestyle changes in their patients by counseling them that obesity and its associated health risks can be reduced in response to an increase in physical activity with or without weight loss. Physical activity (PA) is associated with higher cardiorespiratory fitness values, but additional information is needed on the contributions of specific types and amounts of physical activity (Aires et al., 2010). The purpose of this study is to determine changes and the response in cardiopulmonary functions after exercise testing protocol in ideal subjects (Ortega, 2010) and investigate whether regular exercise was protective against reduced heart rate, a clinically relevant predictor of cardiovascular 113


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exercise and care is taken that they are properly hydrated.  Subjects are advised to wear loose clothing. Vital Signs Measurement

morbidity and mortality, and whether adverse effects of weight gain on heart rate were modified by regular exercise (Haerens et al., 2007). MATERIALS AND METHODS The target population of this study consists of 40 participants. Initial explanation about the aim and purpose of the study, test procedure, method of testing, instructions on how to perform test was given. Explanations about the procedure of parameters to be measured before and after the test were given. Subjects were oriented about Borg's rating of Perceived Exertion and how to rate it. A written consent was taken from all the participants and the study was approved by institutional ethical committee. The participants were selected based on following selection criteria. Inclusion Criteria  Females were included.  Healthy population according to BMI.  Age Between 20 to 30 years.

Position: All subjects were seated in a relaxed sitting posture on a chair Resting Heart Rate: A manual method of taking a heart rate was done by feeling the pulse on the radial side of the wrist for 1 minute. Respiratory Rate: Will be measured by observing the chest movement of the subject for 1 minute. Exercise procedure: All subjects underwent a three minutes step test as short bout of exercise. At the end of each minute, ask the subject to use the RPE scale, from 6 to 20, to describe how hard they feel they are working at that time. Heart rate is measured at 1 minute, 2 minutes and 3 minutes interval for all the participants. RESULTS AND DISCUSSION Data analysis This study was performed with 40 normal BMI females. The age group selected was 20 to 30 years. The basic demographic data obtained included age, BMI, physical activity, heart rate, BP. The outcome measures used in this study are RPE, VO2 max, heart rate, respiratory rate, and BP that are measured before and after exercises. Statistical analysis of the data collected was done using SPSS software. Paired t- test was used to analyze within group data and independent t-test was used to analyze between group values with 95% of level of confidence and p=0.05.

Exclusion criteria Hypertension. History of exertional dyspnea. Known case of Cardiac and respiratory disease.  Diabetes, Hepatic disease, Cancer etc.  Females under hormonal replacement therapy.  Pregnancy. Preparation of Subjects  Before the test the subject should not indulge them into any activities.  Before commencement of test the subjects should be asked to rest for half an hour, so that the vital signs might come down to steady state, than all vital signs will be measured.  Subjects are expected not to have heavy meals/tea/coffee at least 2 hours before   

Table-1: Demographic data showing age, height, weight, heart rate, blood pressure and respiratory rate at baseline

Group

Age

Height

Weight

BMI

Heart Rate

Blood

Respiratory rate

Normal

25±4

159±7

52±3

21±4

77±7

112±5/80±7

13±4

P value

>0.05

>0.05

>0.05

>0.05

>0.05

>0.05

>0.05

Values are express as Mean ± SD 114

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The above table shows the baseline details of both groups in terms of age, height, weight, heart rate, blood pressure and respiratory rate. The age in normal BMI group is 25±4. The height in normal group is 159±7. The weight in normal group is 52±3. The BMI in normal group is 21±4. The heart rate in normal group is 77±7. The blood

pressure in normal group is 112±5/80±7. The respiratory rate in normal group is 13±4. P value for all these variables by using independent t-test at baseline is more than 0.05 and confirms the homogeneity of groups before the commencement of the intervention Table-2: Data analysis in group

Heart Rate

Blood pressure

Respiratory rate

Before

77±7

112±5/80±7

13±4

After

98±6

154±3/112±5

22±9

P value

<0.05

<0.05

<0.05

Values are expressed as Mean ± SD The above table shows with in group data analysis of group by using paired t-test for the outcomes Heart Rate, Blood pressure and Respiratory rate before and after the intervention. The heart rate before is 77±7 and after is 98±6. The blood pressure before 112±5/80±7 and after is 154±3/112±5. The mean ±SD of Respiratory rate

Groups Normal group P value

before 13±4 and after is 22±9. P value for all these variables before and after is less than 0.05 and confirms the statistically significant improvement in all the variables after intervention. Table-5: Normal group after intervention for VO2 max and RPE

VO2 max 34.78±3.2 <0.05

RPE 14±3 <0.05

Values are expressed as Mean ± SD The above table shows the after intervention details of normal group in terms VO2 max and RPE. The VO2 max in group is 34.78±3.2. The RPE in group is 14±3. P value for variables by using independent t-test after intervention is less than 0.05 and confirms the statistically significant difference in group after the intervention. Physical fitness is an important part of life. It is an indicator which shows whether you have the ability to perform and enjoy day to day physical activities with ease. A large percentage of the adult population is relatively physically inactive. In a 1997 survey, only 34% of the population sampled (15 years and older) exercised one or more times a week, citing lack of time as a major factor for remaining inactive. The high incidences of cardiovascular diseases and modern scientific studies connecting physical activity and mortality of adults since the 1950s have resulted in www.ijsir.co.in

increased awareness and research attention in cardiorespiratory fitness of the general population. Numerous surrogate field measures have been developed to predict VO2max or simply categorize individuals. These methods commonly employ stepping, walking and running and more recently, stair-climbing. Thus by having a simple test, individuals can then easily assess their fitness at regular intervals, and at their own convenience (The et al., 2000; Tan et al., 2004). Step tests vary in stepping frequency, step height, test duration, the number of stages and scoring method. Most step tests employ the oxygen demand of the step rate and/or the recovery heart rate (HRrec) from the stepping exercise as the key variables to predict an individual's VO2max. Individuals with different body composition may also impact the results obtained during sub maximal exercise 115


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testing and thus, may affect the prediction of VO2 max. In other words, at any given sub maximal workload, an individual with excess body weight will work at a higher percentage of their VO2max (Tan et al., 2004). Vitals like VO2 max, rate of perceived exertion and post exercise heart rate were taken as markers to evaluate cardiorespiratory fitness. The result of the present study shows that higher is the BMI higher is their exertion level and lower is their cardiorespiratory fitness. It shows that fitness levels of the individuals of age group 20-30 years is poor. CONCLUSION Present study indicates that the major vital of cardiorespiratory fitness that is VO2max and level of perceived exertion of individuals is poor. After the post exercise heart rate, blood pressure and respiratory rate of normal individuals fall in the good range. REFERENCES 1. Aires L., Silva P., Silva G., Santos M.P., Ribeiro J.C., Mota J. Intensity of physical activity, cardiorespiratory fitness, and body mass index in youth. J Phys Act Health. 2010; 7(1):54–59. 2. Haerens L., Deforche B., Maes L., Cardon G., De Bourdeaudhuij I. Physical activity and endurance in normal weight versus overweight boys and girls. J Sports Med Phys Fitness. 2007; 47(3):344–350. 3. He Q.Q., Wong T.W., Du L., Jiang Z.Q., Yu T.S., Qiu H., Gao Y., Liu W.J., Wu J.G. Physi-

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4.

5.

6. 7.

8.

9. 10.

cal activity, cardiorespiratory fitness, and obesity among Chinese children. Prev Med. 2011; 52(2):109–113. Kurth B.M., Schaffrath R.A. The prevalence of overweight and obesity in children and adolesents in Germany. Results of the nationwide children and youth health survey (KiGGS) Bundes-gesundhbl Gesundheits for sch -Gesundheitsschutz. 2007; 50: 736–743. Ortega F.B. Cardiovascular fitness modifies the associations between physical activity and abdominal adiposity in children and adolescents: the European Youth Heart Study. BJSM. 2010; 44:256–262. Wang Y., Lobstein T. Worldwide trends in childhood overweight and obesity. IJPO. 2006; 1(1):11–25. World Health Organization. WHO regional publications. European series; No. 97. Kopenhagen: 2002. The European Health report 2002. World Health Organization. WHO technical report series: 894. Geneva: 1999. Obesity: preventing and managing the global epidemic: report of a WHO consultation. Teh K.C., Aziz A.R. et al. A Stair-Climb Test of Cardiorespiratory Fitness for Singapore. Singapore Med. J. 2000; 41(12): 588-594. Tan H.Y.F., Aziz A.R., Teh K.C., Chia Y.H.M. Reliability of the Stair-Climb Test (SCT) of Cardiorespiratory Fitness A dv. Exerc. S ports Physiol. 2004; 10(3):77-83.

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EFFECT OF A SHORT BOUT OF EXERCISE ON CARDIORESPIRATORY CHANGES IN IDEAL WEIGHT POPULATION 1

1

2

Mohammad Shahid Ali , Aisha Ansari , Jagatheesan Alagesan , *Prathap S

1,3

1

Faculty of Medical and Paramedical sciences, Himalayan University, Itanagar, Arunachal Pradesh, India; 2College of health sciences, Gulf Medical University, Ajman, UAE; 3Aarogyam Hospital Reengas, Sikar,Rajasthan,India *Address for Correspondence: Dr. Prathap S, Aarogyam Hospital, Reengas,Sikar,Rajasthan,India Email : bhanwarpunit6@gmail.com

ABSTRACT Heart function can be described as the various measures of efficiency for the heart and circulatory systems during rest and activity and to investigate whether regular exercise was protective against reduced heart rate, or adverse effects of obesity and weight gain on heart rate were modified by regular exercise. In this study effect of a short bout of exercise on cardiorespiratory changes in ideal weight population were analyzed.Sedentary population, according to Baecke's Questionnaire both sexes, between 20 and 30 years with Body Mass Index (BMI) 18.5 to 24.9 were recruited using Purposive sampling (N = 50).The results were obtained using t-test. The ideal weight group is homogenous at the baseline and showed statistically significant changes after intervention with short bout of exercises in Rate of Perceived Exertion Scale, Respiratory Rate and Heart Rate.Cardiorespiratory changes in ideal weight population following short bout of exercise concludes that increasing levels of physical activity in subjects are associated with an increase in cardiorespiratory fitness. Keywords: BMI, Cardio Respiratory Changes, RPE, Heart Rate, Respiratory Rate INTRODUCTION A sedentary lifestyle is a type of lifestyle with little or no physical activity. A person living a sedentary lifestyle is often sitting or lying, while reading, socializing, watching television, playing video games, or using a mobile phone/computer for much of the day (Lobstein et al., 2006).It is commonly found in boththe developed and developing world. A lack of physical activity is one of the leading causes of preventable death worldwide.Several studies showed that regular physical activity can improve the health of older people and contribute to the primary and secondary prevention of many chronic diseases, including sarcopenia (Zech et al., 2011).Furthermore, a sedentary lifestyle is associated with many chronic diseases, the change inbody composition (increased fat and decreased muscle mass) and development of premature death (Kim et al., 2012).Research evaluating in individuals who are physically active or sedentary practices suggests that regular physical activity can improve muscle mass and grip strength and lower limb mobility www.ijsir.co.in

(Sherrington et al., 2004).With the sedentary lifestyle on the rise, fitness has become more and more essential. Coronary heart disease is the leading cause of death worldwide, responsible for over 7 million deaths annually. Indian Asians (people originating from India, Pakistan, Bangladesh and Sri Lanka) comprise one quarter of the globe's population and are at high risk of developing CHD. Recent estimates from the Global Burden of Disease (GBD) 2010 Study (Lozano et al., 2010) indicate that CHD deaths are highest in South Asia, increasing by 87.8% between 1990 and 2010, second only to East Asia. Cardiovascular exercise is typically performed to improve and maintain cardiovascular health. Aside from endurance competitors (triathletes, cyclists, marathon runners, etc.), recreationally active men and women should be exercising at an intensity that promotes optimal heart health. However, it is not always clear as to what intensities one should be exercising at to facilitate the greatest return. For years exercisers have been 117


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using both heart rate (HR) values and ratings of perceived exertion (RPE) to classify intensities during cardiovascular training. The intensity in which effort is expended is essential to the elaboration and control of any exercise program. Heart rate and perceived effort are the most frequently used indicators for the control of the intensity of effort in water exercises (Graef and Kruel, 2006). During exercise testing, the quantity of blood pumped by the heart increases to match the increased skeletal muscle demand. Heart rate (HR) monitoring is a method commonly used to determine and assess exercise intensity levels. Exercise intensity is a key component of the training response. Therefore, it is important to understand the factors that can influence HR during exercise, so modifications can be made when establishing training heart rate. Rate of Perceived Exertion (RPE) is used as a means to quantify the subjective feelings of the intensity of exercise. The scale describes a range of intensity from resting to maximal energy outputs and is used as a visual aid to exercisers in keeping their efforts in the effective training zone, the rating range from 6-20 (Panton et al.1996). Over the past two decades cardiorespiratory fitness, i.e. the efficiency of the respiratory and cardiovascular systems, has been the subject of a very large number of studies. In contrast, it is only recently that the cardiorespiratory fitness of the general adult population, aged from 20 to 30 years, has received much attention. This is due to the fact that diseases of the respiratory and cardiovascular systems have become a major cause of adult deaths in Western nations. Previous studies were done by Clifton and Skalon(May 2006), in normal physically active male and female to find out the correlation of heart rate and rate of perceived exertion (RPE) but very few studies has been done on sedentary individuals and overweight individuals to determine if the Rate of Perceived Exertion scale does accurately assess the subject's work rate and can be used as a helpful means of obtaining the work rate of an individual during exercise testing and in some cases could be used in lieu of HR (Clintof and Skalon,2006).So this study aimed to compare on ideal weight adults adults to determine if the Rate of Perceived Exertion scale 118

does accurately assess the subject's work rate and can be used as a helpful means of obtaining the work rate of an individual during exercise testing and in some cases could be used in lieu of Heart Rate. MATERIALS AND METHODS Inclusion Criteria  Sedentary population (N= 50), according to Baecke's Questionnaire both sexes, between 20 and 30 years with Body Mass Index (BMI) 18.5 to 24.9.  Subjects not undergoing any exercise program in the form of training. Exclusion criteria  Hypertensive subjects.  History of exertional dyspnoea.  Clinically diagnoses cardiovascular and cardiorespiratory diseases.  Medical conditions like Diabetes, Hepatic disease, Cancer, etc.  Orthopaedic problems such as recent fractures, joint and muscle pathologies.  Difficulty in following the commands and procedure.  Women under hormonal replacement therapy.  Alcoholics and Smokers. Procedure The target population of this study consists of 50 participants. Initial explanation about the aim and purpose of the study, test procedure, method of testing, instructions on how to perform test was given. Explanations about the procedure of parameters to be measured before and after the test were given. Subjects were oriented about Borg's rating of Perceived Exertion and how to rate it. A written consent was taken from all the participants and the study was approved by institutional ethical committee. The participants were selected based on following selection criteria. Subject preparation  Before the test the subject should not indulge them into any activities.  Before commencement of test the subjects should be asked to rest for half an hour, so that the vital signs might come down to steady state, than all vital signs were measured.  Subjects were expected not to have heavy www.ijsir.co.in


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meals/tea/coffee atleast 2 hours before exercise and care is taken that they are properly hydrated.  Subjects were advised to wear loose clothing. Vital Signs Measurement Position: Relaxedsitting posture on a chair. Resting Heart Rate: A m a n u a l m e t h o d o f taking a heart rate will be done by feeling the pulse on the radial side of the wrist for 1 minute. Respiratory Rate: Will be measured by observing the chest movement of the subject for 1 minute. Test procedure  Subjects are asked to step up and down (up-up; down-down) at the rate set by metronome.  At the end of 1 minute, the subject will be asked to rate their rate of perceived exertion and pulse rate was measured and the values will be noted.  Again the subject was made to step up and down for 2 minutes, and asked to rate their rate of perceived exertion and pulse rate will be measured and the values will be noted.  Once again the subject was made to step up and down for 3 minutes, and asked to rate their rate of perceived exertion pulse rate will be

measured and the values will be noted. Scoring procedure is remaining standing after test. Beginning 5 seconds after the cessation of test, take a 15-second pulse count. Multiply the 15-second count by 4 to express the score in beats per minute (bpm). Outcome measures  Heart Rate  Respiratory Rate  Rate of Perceived Exertion RESULTS AND DISCUSSION This study was performed with 50 ideal weight BMI adults. The age group selected was 20 to 30 years. The basic demographic data obtained included age, height, weight, BMI, heart rate and respiratory rate. The outcome measures used in this study are RPE, and heart rate that are measured before and after exercises. Statistical analysis of the data collected was done using SPSS software. Paired t- test was used to analyze the within group data and independent t-test was used to analyze between group values with 95% of level of confidence and p=0.05. Table-1: Demographic data showing age, height, weight, heart rate and respiratory rate at baseline 

Group

Age

Height

Weight

BMI

Heart Rate

Respiratory rate

Ideal weight group

25±4

159±7

52±3

21±4

77±7

13±4

P value

>0.05

>0.05

>0.05

>0.05

>0.05

>0.05

Values are expressed as Mean ± SD

The above table shows the baseline details of group in terms of age, height, weight, heart rate and respiratory rate. The age in Ideal weight group is 25±4. The height in Ideal weight group is 159±7. The weight in Ideal weight group is 52±3. The BMI in Ideal weight group is 21±4. The Heart rate in Ideal weight group is 77±7. The

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Respiratory rate in Ideal weight group is 13±4. P value for all these variables by using independent t-test at baseline is more than 0.05 and confirms the homogeneity of groups before the commencement of the intervention. Table-2: SEX distribution among groups

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Group

Male Female

Total

Ideal weight group

27

23

50

Total

51

49

100

Values are expressed as Mean ± SD The above shows sex distribution among the both groups. In ideal weight group there were 27 males and 23 females.

Table-3: Data analysis in ideal weight group

Heart Rate

Respiratory rate

RPE

Before

77±7

13±4

6±0

After

98±6

22±9

13±7

P value

<0.05

<0.05

<0.05

Values are express as Mean ± SD The above table shows with in group data analysis of ideal weight group by using paired t-test for the outcomes Heart Rate, Respiratory rate and RPE before and after the intervention. The Heart Rate before is 77±7 and after is 98±6. The Respiratory rate before 13±4 and after is 22±9. The RPE before 6±0 and after is 13±7. P value for all these variables before and after is less than 0.05 and confirms the statistically significant improvement in all the variables after intervention. Aires et al (2010) did a study to analyze the relation between body mass index (BMI), Cardiorespiratory Fitness (CRF), and levels of physical activity (PA) from sedentary to very vigorous intensities, measured by accelerometry, in students from a middle and high school. This cross-sectional study included 111 children and adolescents. Pearson's correlation was used to analyze correlations between all variables. This paper provided evidence that BMI was inversely and significantly correlated with CRF. Low CRF is strongly associated with obesity, which highlights the importance of increasing CRF for a protective effect even in youth. Physical fitness is an important part of life. It is an indicator which shows whether you have the ability to perform and enjoy day to day physical activities with ease. A large percentage of the adult population is relatively physically inactive. 120

In a 1997 survey, only 34% of the population sampled (15 years and older) exercised one or more times a week, citing lack of time as a major factor for remaining inactive. The high incidences of cardiovascular diseases and modern scientific studies connecting physical activity and mortality of adults since the 1950s have resulted in increased awareness and research attention in cardiorespiratory fitness of the general population. Leisure time physical activity increased among normal weight participants. Adolescents of normal weight had better cardiorespiratory performance than those classified as overweight at both assessment points. BMI - adjusted physical activity was a significant determinant for cardiorespiratory performance among overweight adolescents, and very active overweight adolescents had similar cardiorespiratory performance levels as moderately active adolescents of normal weight. The results of the present study support the idea that the physical activity has the great importance for the cardiorespiratory performance in adolescents. Overweight adolescents, in particular, benefit from higher levels of physical activity. Several studies (Fogelholm et al., 2008 ;Ortega, 2010) confirmed that physical activity and physical fitness are equally important for health. www.ijsir.co.in


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In the following the results will be discussed with reviews analyzing only the relationship between two parameters, because no comparable reviews were found. The different strengths of the correlations between the three parameters may be at least in part attributed to the different measurements of physical activity. For instance, two studies (Fogelholm et al., 2008; Ortega,2010) assessed physical activity via questionnaire, one via accelerometer and one via activity monitor and questionnaire, and the collection period of objectively measured physical activity ranged from three to six days. In addition, the two studies that measured physical activity subjectively omitted reporting details on their measurement instruments.

5.

6.

7.

CONCLUSION This study on cardiorespiratory changes in ideal weight population following short bout of exercise concludes that increasing levels of physical activity in subjects are associated with an increase in cardiorespiratory fitness. REFERENCES 1. Aires L., Silva P., Silva G., Santos M.P., Ribeiro J.C., Mota J. Intensity of physical activity, cardiorespiratory fitness, and body mass index in youth. J Phys Act Health. 2010; 7(1):54–59. 2. Clintof A., Skalon T. The Relation of Heart Rate and the Rate of Perceived Exertion British Journal of Sports Medicine 2006; 160(11):1621-1628. 3. Graef F.I., Kruel L.F.M. Heart rate and perceived exertion at aquatic environment: differences in relation to land environment and applications for exercise prescription – a review. Rev Bras Med Esporte. 2006; 12(4): 198e-104e. 4. Fogelholm M., Stigman S., Huisman T., Metsamuuronen J. Physical fitness in

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8.

9.

10.

11.

adolescents with normal weight and overweight. Scand J Med Sci Sports. 2008; 18(2): 162–170. Kim H.K., Suzuki T., Saito K., Yoshida H., Kobayashi H., Kato et al. Effects of Exercise and Amino Acid Supplementation on Body and Physical Function in CommunityDwelling Elderly Japanese Sarcopenic Women: A Randomized Controlled Trial. J Am Geriatr Soc. 2012, 60:16-23. Lobstein T., Baur L., Uauy R. IASO International Obesity Task Force: obesity in children and young people: a crisis in public health. Obes Rev. 2004;5(1):4–104. Lozano R., Naghavi M., Foreman K., Lim S., Shibuya K., Aboyans et al. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012;380 (9859):2095–2128. Ortega F.B. Cardiovascular fitness modifies the associations between physical activity and abdominal adiposity in children and adolescents: the European Youth Heart Study. BJSM. 2010; 44:256–262. Panton L.B., Graves J.E., Pollock M.L., Garzarella et al. Relative heart rate, heart rate reserve, and VO2 during submaximal exercise in the elderly.J Gerontol A Biol Sci Med Sci.1996; 51(4):165-71. Sherrington C., Lord S.R., Finch C.F. Physical activity interventions to prevent falls among older people: update of the evidence. J Sci Med Sport. 2004; 7(1):43-51. Zech A.,Steib S., Sportwiss D., Freiberger E., Pfeifer K. Functional Muscle Power Testing in Young, Middle-Aged, and CommunityDwelling Nonfrail and Prefrail Older Adults. Arch Phys Med Rehabil 2011; 92(6):967-71.

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ABOUT SKY INSTITUTE Sky Institute, a constituent institution of BALAJI FOUNDATION established under Societies Registration Act 1860, has been functioning from the year 2006. Sky institute aims to provide quality education to young students with a view to develop socially responsible future technologists and business leaders with good communication spirit with a commitment to economic development with a strong multi disciplinary knowledge base and technical/ managerial skills. Graduates of Sky Institute will be well prepared to succeed in an increasingly competitive global economy. With a focus on multidisciplinary research and education and learning model, that emphasizes active learning, Sky Institute aspires to be globally known for education, research, innovation at the intersection of disciplines. The institute provides a professional learning environment that acts as a catalyst for the exponential growth of students as well as extracurricular abilities. It conducts courses at the level of under graduate and post graduate followed by research courses leading to M Phil and Ph.D. in all subjects in association with universities. VISION  To be known globally for education, research and innovation at the intersection of disciplines  Improving lives through education, research and innovation  To be an outstanding higher learning and research Institution of excellence ever in pursuit of horizons to build self reliant global citizens through assured quality educational programs. MISSION  To promote sustainable development of the Higher Education consistent with statutory and regulatory requirements.

 To plan and continuously provide necessary

infrastructure learning resources required for quality education and innovation.  To stimulate to extend the frontiers of knowledge through faculty development and continuing education programs.  To make research a significant activity involving staff, students and society.  To promote industry/ organization interaction/ collaborations with regional national/ international bodies.  To establish system for communication among all stake holders for vision oriented growth. INFRASTRUCTURE Sky Institute is having sufficient infrastructure to undertake educational and research programs in various disciplines. Presently, it has two premises in Lucknow one in Gomti Nagar and another at Kursi Road with sufficient space and office infrastructure including Wi-Fi internet facility, telephone and computers. In addition, Biotechnological Research Laboratory with adequate equipment facility has been setup in its premises situated at Kursl Road, Lucknow with main emphasis to undertake multidisciplinary research and development (R & D) projects of societal benefits in frontier areas of biotechnology (industrial biotechnology, m e d i c a l b i o t e c h n o l o g y, e n v i r o n m e n t a l biotechnology and agricultural biotechnology) and allied areas, which will also help in developing trained and highly skilled human resource in science and technology (S & T) sector for the benefit of the country. In addition, Sky Institute has also established a computer laboratory and is strengthening its library in this premises The institute is also having a conference hall in its premises situated at Kursi Road, Lucknow.


RESEARCH The Sky Institute gives a lot of emphasis on research in various areas of science, technology, engineering health , agriculture andalso in subjects related to humanities and education with a view to develop skilled human resources in higher education and research sector. Sky institute has started to publish a bi-annual scientific journal "International Journal of Scientific and Innovative Research (IJSIR)" :PISSN 2347- 2189, E ISSN 2347-4971 (website www.ijsir.co.in), which publishes innovative research papers, reviews, minireviews, short communications and notes dealing with all branches of science, technology, engineering, health and agriculture. The institute is also developed a research laboratory in the area of biotechnology in order to conduct multidisciplinary R & D work in frontier areas of biotechnology and allied disciplines for the benefit of society and ailing humanity.

science and engineering graduates both at under graduate and post graduate level as part of the fulfillment of their graduate and post graduate courses. The Biotechnological Research Laboratory set up at Sky Institute will help science and engineering graduates/post graduates in building their scientific and technological skill in the area of biotechnology which has enormous scope in research and industries. The Institute also conducts summer training programs for under graduates and post graduates (science and engineering) in various areas including biotechnology, herbal sciences, computer sciences etc. for upgrading their knowledge and technical skill which help them immensely in building their careers in education, research and industry sectors. EDUCATIONAL PROGRAMS At present, Sky Institute is running various educational courses in collaboration with universities.

TRAINING The Sky Institute conducts training programs for

CONTACT DETAILS: Website: www.skylucknow.com Campus 1: SKY INSTITUTE Shivam Palace II, Near Sports College, Opp. Petrol Pump, Mishrpur, KursiRoad, Lucknow, PIN 226026 Mobile :+91 9839414406, +91 8417009592, +91 9794849800 e-Mail : balajisky169@gmail.com Campus 2: SKY INSTITUTE 4/285, Vivek Khand, Opp. Petrol Pump, Patrakarpuram, Gomti Nagar, Lucknow, PIN 226010 Mobile :+919839414406, +91-522-4107526 e-Mall : mohitsky25@gmail.com


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