Search results for: Saurabh Rawat

Authors: Saurabh Satija, Munish Garg

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Present work reports an efficient extraction method using microwaves based solvent–sample duo-heating mechanism, for the extraction of an important anti-diabetic plant Tinospora cordifolia from AYUSH system for estimation of berberine content. The process is based on simultaneous heating of sample matrix and extracting solvent under microwave energy. Methanol was used as the extracting solvent, which has excellent berberine solubilizing power and warms up under microwave attributable to its great dispersal factor. Extraction conditions like time of irradition, microwave power, solute-solvent ratio and temperature were optimized using Taguchi design and berberine was quantified using high performance thin layer chromatography. The ranked optimized parameters were microwave power (rank 1), irradiation time (rank 2) and temperature (rank 3). This kind of extraction mechanism under dual heating provided choice of extraction parameters for better precision and higher yield with significant reduction in extraction time under optimum extraction conditions. This developed extraction protocol will lead to extract higher amounts of berberine which is a major anti-diabetic moiety in Tinospora cordifolia which can lead to development of cheaper formulations of the plant Tinospora cordifolia and can help in rapid prevention of diabetes in the world.

Keywords: berberine, microwave, optimization, Taguchi

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Authors: Saurabh Farkya, Govinda Surampudi

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Optical Character Recognition is one of the current major research areas. This paper is focussed on recognition of Devanagari script and its sound generation. This Paper consists of two parts. First, Optical Character Recognition of Devnagari handwritten Script. Second, speech synthesis of the recognized text. This paper shows an implementation of support vector machines for the purpose of Devnagari Script recognition. The Support Vector Machines was trained with Multi Domain features; Transform Domain and Spatial Domain or Structural Domain feature. Transform Domain includes the wavelet feature of the character. Structural Domain consists of Distance Profile feature and Gradient feature. The Segmentation of the text document has been done in 3 levels-Line Segmentation, Word Segmentation, and Character Segmentation. The pre-processing of the characters has been done with the help of various Morphological operations-Otsu's Algorithm, Erosion, Dilation, Filtration and Thinning techniques. The Algorithm was tested on the self-prepared database, a collection of various handwriting. Further, Unicode was used to convert recognized Devnagari text into understandable computer document. The document so obtained is an array of codes which was used to generate digitized text and to synthesize Hindi speech. Phonemes from the self-prepared database were used to generate the speech of the scanned document using concatenation technique.

Keywords: Character Recognition (OCR), Text to Speech (TTS), Support Vector Machines (SVM), Library of Support Vector Machines (LIBSVM)

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Authors: Revoti Prasad Bora, Saurabh Yadav, Nikita Katyal

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In the context of educational data mining, the use case of extracting information from images containing both text and diagrams is of high importance. Hence, document analysis requires the extraction of diagrams from such images and processes the text and diagrams separately. To the author’s best knowledge, none among plenty of approaches for extracting tables, figures, etc., suffice the need for real-time processing with high accuracy as needed in multiple applications. In the education domain, diagrams can be of varied characteristics viz. line-based i.e. geometric diagrams, chemical bonds, mathematical formulas, etc. There are two broad categories of approaches that try to solve similar problems viz. traditional computer vision based approaches and deep learning approaches. The traditional computer vision based approaches mainly leverage connected components and distance transform based processing and hence perform well in very limited scenarios. The existing deep learning approaches either leverage YOLO or faster-RCNN architectures. These approaches suffer from a performance-accuracy tradeoff. This paper proposes a U-Net based architecture that formulates the diagram extraction as a segmentation problem. The proposed method provides similar accuracy with a much faster extraction time as compared to the mentioned state-of-the-art approaches. Further, the segmentation mask in this approach allows the extraction of diagrams of irregular shapes.

Keywords: computer vision, deep-learning, educational data mining, faster-RCNN, figure extraction, image segmentation, real-time document analysis, text extraction, U-Net, YOLO

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Authors: Saurabh Shukla, G. N. Pandey

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In recent times, oil exploration and monitoring in on-shore areas have gained much importance considering the fact that in India the oil import is 62 percent of the total imports. Thus, architectural model like wireless sensor network to monitor on-shore deep sea oil well is being developed to get better estimate of the oil prospects. The problem we are facing nowadays that we have very few restricted areas of oil left today. Countries like India don’t have much large areas and resources for oil and this problem with most of the countries that’s why it has become a major problem when we are talking about oil exploration in on-shore areas also the increase of oil prices has further ignited the problem. For this the use of wireless network system having relative simplicity, smallness in size and affordable cost of wireless sensor nodes permit heavy deployment in on-shore places for monitoring oil wells. Deployment of wireless sensor network in large areas will surely reduce the cost it will be very much cost effective. The objective of this system is to send real time information of oil monitoring to the regulatory and welfare authorities so that suitable action could be taken. This system architecture is composed of sensor network, processing/transmission unit and a server. This wireless sensor network system could remotely monitor the real time data of oil exploration and monitoring condition in the identified areas. For wireless sensor networks, the systems are wireless, have scarce power, are real-time, utilize sensors and actuators as interfaces, have dynamically changing sets of resources, aggregate behaviour is important and location is critical. In this system a communication is done between the server and remotely placed sensors. The server gives the real time oil exploration and monitoring conditions to the welfare authorities.

Keywords: sensor, wireless sensor network, oil, sensor, on-shore level

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Authors: Pankaj Singh Rawat, Rajeew Kumar, Pradeep Ram, Priyanka Pandey

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Wheat is an important cereal crop for food security. Boosting the wheat production and productivity is the major challenge across the nation. Good quality of seed is required for maintaining optimum plant stand which ultimately increases grain yield. Ensuring a good germination is one of the key steps to ensure proper plant stand and moisture assurance during seed germination may help to speed up the germination. The tiny size of nanoparticles may help in entry of water into seed without disturbing their internal structure. Considering above, a laboratory experiment was conducted during 2012-13 at G.B. Pant University of Agriculture and Technology, Pantnagar, India. The completely randomized design was used for statistical analysis. The experiment was conducted in two phases. In the first phase, the appropriate concentration of nanoparticles for seed treatment was screened. In second phase seed soaking hours of nanoparticles for better seed germination were standardized. Wheat variety UP2526 was taken as test crop. Four nanoparticles (TiO₂, ZnO, nickel and chitosan) were taken for study. The crop germination studies were done in petri dishes and standard package and practices were used to raise the seedlings. The germination studies were done by following standard procedure. In first phase of the experiment, seeds were treated with 50 and 300 ppm of nanoparticles and control was also maintained for comparison. In the second phase of experiment, seeds were soaked for 4 hours, 6 hours and 8 hours with 50 ppm nanoparticles of TiO₂, ZnO, nickel and chitosan along with control treatment to identify the soaking time for better seed germination. Experiment revealed that the application of nanoparticles help to enhance seed germination. The study revealed that seed treatment with  nanoparticles at 50 ppm concentration increases root length, shoot length, seedling length, shoot dry weight, seedling dry weight, seedling vigour index I and seedling vigour index II as compared to seed soaking at 300 ppm concentration. This experiment showed that seed soaking up to 4 hr was better as compared to 6 and 8 hrs. Seed soaking with nanoparticles specially TiO₂, ZnO, and chitosan proved to enhance germination and seedling growth indices of wheat crop.

Keywords: nanoparticles, seed germination, seed soaking, wheat

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Authors: Saurabh Basu, Sudin Ganguly

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Conductance in graphene nanoribbons (GNR) in presence of magnetic (for example, Iron) and non-magnetic (for example, Gold) adatoms are explored theoretically within a Kane-Mele model for their possible spintronic applications and topologically non-trivial properties. In our work, we have considered the magnetic adatoms to induce a Rashba spin-orbit coupling (RSOC) and an exchange bias field, while the non-magnetic ones induce an RSOC and an intrinsic spin-orbit (SO) coupling. Even though RSOC is present in both, they, however, represent very different physical situations, where the magnetic adatoms do not preserve the time reversal symmetry, while the non-magnetic case does. This has important implications on the topological properties. For example, the non-magnetic adatoms, for moderately strong values of SO, the GNR denotes a quantum spin Hall insulator as evident from a 2e²/h plateau in the longitudinal conductance and presence of distinct conducting edge states with an insulating bulk. Since the edge states are protected by time reversal symmetry, the magnetic adatoms in GNR yield trivial insulators and do not possess any non-trivial topological property. However, they have greater utility than the non-magnetic adatoms from the point of view of spintronic applications. Owing to the broken spatial symmetry induced by the presence of adatoms of either type, all the x, y and z components of the spin-polarized conductance become non-zero (only the y-component survives in pristine Graphene owing to a mirror symmetry present there) and hence become suitable for spintronic applications. However, the values of the spin polarized conductances are at least two orders of magnitude larger in the case of magnetic adatoms than their non-magnetic counterpart, thereby ensuring more efficient spintronic applications. Further the applications are tunable by altering the adatom densities.

Keywords: magnetic and non-magnetic adatoms, quantum spin hall phase, spintronic applications, spin polarized conductance, time reversal symmetry

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Authors: Srikrishna Pramanik, Sree Chithra, Saurabh Rai, Sameeksha Agrawal, Debanggana Shil, Saptarshi Mukherjee

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The understanding of interactions between organic chromophores and biologically useful luminescent noble metal nanoclusters (NCs) leading to an energy transfer process that has applications in light-harvesting materials is still in its nascent stage. This work describes a photoluminescent supramolecular assembly, made in two stages, employing an energy transfer process between silver (Ag) NCs as the donor and a host-guest system as the acceptor that can find potential applications in diverse fields. Initially, we explored the host-guest chemistry between a cationic guest, Ethidium Bromide and the anionic host Cucurbit[8]uril using spectroscopic and calorimetric techniques to decipher their interaction mechanism in modulating photophysical properties of the chromophore. Next, we synthesized a series of blue-emitting AgNCs using different templates such as protein, peptides, and cyclodextrin. The as-prepared AgNCs were characterized by various spectroscopic techniques. We have established that these AgNCs can be employed as donors in the FRET process with the above acceptor for FRET-based emission color tuning. Our in-depth studies revealed that surface ligands play a key role in modulating FRET efficiency. Overall, by employing a non-covalent strategy, we have tried to develop FRET pairs using blue-emitting NCs and a host-guest complex, which could find potential applications in constructing advanced white light-emitting, anti-counterfeiting materials, and developing biosensors.

Keywords: absorption spectroscopy, cavities, energy transfer, fluorescence, fluorescence resonance energy transfer

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Authors: Shveta Bathla, Preeti Rawat, Sudarshan Kumar, Rubina Baithalu, Jogender Singh Rana, Tushar Kumar Mohanty, Ashok Kumar Mohanty

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Pregnancy is a complex process which includes series of events such as fertilization, formation of blastocyst, implantation of embryo, placental formation and development of fetus. The success of these events depends on various interactions which are synchronized by endocrine interaction between a receptive dam and competent embryo. These interactions lead to change in expression of hormones and proteins. But till date no protein biomarker is available which can be used to detect successful completion of these events. We employed quantitative proteomics approach to develop putative serological biomarker which has diagnostic applicability for early detection of pregnancy in cows. For this study, sera were collected from control (non-pregnant, n=6) and pregnant animals on successive days of pregnancy (7, 19, 45, n=6). The sera were subjected to depletion for removal of albumin using Norgen depletion kit. The tryptic peptides were labeled with iTRAQ. The peptides were pooled and fractionated using bRPLC over 80 min gradient. Then 12 fractions were injected to nLC for identification and quantitation in DDA mode using ESI. Identification using Mascot search revealed 2056 proteins out of which 352 proteins were differentially expressed. Twenty proteins were upregulated and twelve proteins were down-regulated with fold change > 1.5 and < 0.6 respectively (p < 0.05). The gene ontology studies of DEPs using Panther software revealed that majority of proteins are actively involved in catalytic activities, binding and enzyme regulatory activities. The DEP'S such as NF2, MAPK, GRIPI, UGT1A1, PARP, CD68 were further subjected to pathway analysis using KEGG and Cytoscape plugin Cluego that showed involvement of proteins in successful implantation, maintenance of pluripotency, regulation of luteal function, differentiation of endometrial macrophages, protection from oxidative stress and developmental pathways such as Hippo. Further efforts are continuing for targeted proteomics, western blot to validate potential biomarkers and development of diagnostic kit for early pregnancy diagnosis in cows.

Keywords: bRPLC, Cluego, ESI, iTRAQ, KEGG, Panther

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Authors: Shakti S. Acharya, V. R. R. Medicherla, Rajeev Rawat, Komal Bapna, Deepnarayan Biswas, Khadija Ali, K. Maiti

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The discovery of invar effect in 35% Ni concentration Fe1-xNix alloy has stimulated enormous experimental and theoretical research. Elemental Fe and low Ni concentration Fe1-xNix alloys which possess body centred cubic (bcc) crystal structure at ambient temperature and pressure transform to hexagonally close packed (hcp) phase at around 13 GPa. Magnetic order was found to be absent at 11K for Fe92Ni8 alloy when subjected to a high pressure of 26 GPa. The density functional theoretical calculations predicted substantial hyperfine magnetic fields, but were not observed in Mossbaur spectroscopy. The bulk modulus of fcc Fe1-xNix alloys with Ni concentration more than 35%, is found to be independent of pressure. The magnetic moment of Fe is also found be almost same in these alloys from 4 to 10 GPa pressure. Fe1-xNix alloys exhibit a complex microstructure which is formed by a series of complex phase transformations like martensitic transformation, spinodal decomposition, ordering, mono-tectoid reaction, eutectoid reaction at temperatures below 400°C. Despite the existence of several theoretical models the field is still in its infancy lacking full knowledge about the anomalous properties exhibited by these alloys. Fe1-xNix alloys have been prepared by arc melting the high purity constituent metals in argon ambient. These alloys have annealed at around 3000C in vacuum sealed quartz tube for two days to make the samples homogeneous. These alloys have been structurally characterized by x-ray diffraction and were found to exhibit a transition from bcc to fcc for x > 0.3. Ni 2p core levels of the alloys have been measured using high resolution (0.45 eV) x-ray photoelectron spectroscopy. Ni 2p core level shifts to lower binding energy with respect to that of pure Ni metal giving rise to negative core level shifts (CLSs). Measured CLSs exhibit a linear dependence in fcc region (x > 0.3) and were found to deviate slightly in bcc region (x < 0.3). ESCA potential model fails correlate CLSs with site potentials or charges in metallic alloys. CLSs in these alloys occur mainly due to shift in valence bands with composition due to intra atomic charge redistribution.

Keywords: arc melting, core level shift, ESCA potential model, valence band

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Authors: Bharat Rawat, Shekhar Rajbhandari, Yadav Bhatta, Jay Prakash Jaiswal, Shivaji Bikram Silwal, Rajiv Shrestha, Shova Sunuwar

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Introduction: The honey produced by the bees fed on Rhobdodendron species containing grayanotoxin is known as mad honey. Grayanotoxin is found in honey obtained from the nectar of Rhododendron species growing on the mountains of the Black Sea region of Turkey and also in Japan, Nepal, Brazil, parts of North America, and Europe. Although the incidence of grayanotoxin poisoning is rare, there is concern that the number of cases per year will rise with the increasing demand for organic products. Mad honey intoxication might present with mild symptoms of cardiovascular, gastrointestinal and neurological systems or might also present with a life-threatening form with AV block and cardiovascular collapse. In this article, we describe the summary of five cases, which came to our hospital with mad honey related cardiac complications. Findings: In last one year, five cases presented in the emergency department with sudden onset of Loss of consciousness, dizziness, shortness of breath. They felt difficulty after the consumption of 1-3 teaspoonful of wild honey. The honey was brought from most of the rural parts of Nepal like khotang. Some of them also came with vomiting, dizziness, and loose stool. On examination, most of them had severe bradycardia and low blood pressure. No abnormalities were detected on systemic examinations. In one patient, ECG and cardiac enzymes showed features of the acute coronary syndrome, but his treadmill test done few days later was normal. All patients were managed with inj. Atropine, I/V normal saline, and other supportive measures and discharged in a stable condition within one or two days. Conclusions: Rhododendrons is the national flower of Nepal. The specific species of rhododendron found in Nepal which contains the toxin is not known. Bees feeding on these rhododendrons are known to transfer the grayanotoxin to the honey they produce. Most symptoms are mild and resolve themselves without medical intervention. Signs and symptoms of grayanotoxin poisoning rarely last more than 24 hours and are usually not fatal. Some signs of mad honey poisoning include Bradycardia, Cardiac arrhythmia, Hypotension, Nausea and Vomiting. They respond to close monitoring and appropriate supportive treatment. Normally, patients recover completely with no residual damage to the heart or its conduction system.

Keywords: rhobdodendron, honey, grayanotoxin, bradycardia

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Authors: Alok Kumar Yadav, Saurabh Saraswat, Preeti Sirohi, Manjoo Rani, Sameer Srivastava, Manish Pratap Singh, Nand K. Singh

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The development of antibiotic resistance in bacteria is increasing at an alarming rate, and this is considered as one of the most serious threats in the history of medicine, and an alternative solution should be derived so as to tackle this problem. In many countries, people use the medicinal plants for the treatment of various diseases as these are cheaper, easily available and least toxic. Syzygium cumini is used for the treatment of various kinds of diseases but their mechanism of action is not reported. The antimicrobial activity of Syzygium cumini was tested by the well diffusion assay and zone of inhibition was reported to be 20.06 mm as compared to control with MIC of 0.3 mg/ml. Genomic DNA fragmentation of Bacillus subtilis revealed apoptosis and FE-SEM indicate cell wall cracking on several intervals of time. Propidium iodide staining results showed that few bacterial cells were stained in the control and population of stained cells increase after exposing them for various period of time. Flow cytometric kinetic data analysis on the membrane permeabilization in bacterial cell showed the significant contribution of antimicrobial potential of the seed extract on antimicrobial-induced permeabilization. Two components of Syzygium cumini methanolic seed extract was found to be quite active against four enzymes like PDB ID- 1W5D, 4OX3, 3MFD and 5E2F which have a very crucial role in membrane synthesis in Bacillus subtilis by in silico analysis. Through in silico analysis, lupeol showed highest binding energy for macromolecule 1W5D and 4OX3 whereas stigmasterol showed the highest binding energy for macromolecule 3MFD and 5E2F respectively. It showed that methanolic seed extract of Syzygium cumini can be used for the inhibition of foodborne infections caused by Bacillus subtilis and also as an alternative of prevalent antibiotics.

Keywords: antibiotics, Bacillus subtilis, inhibition, Syzygium cumini

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Authors: Mohd Imtiaz S, Saurabh Jain, Pothiraj K.

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In today’s highly competitive passenger vehicle market, comfortable driving experience is one of the key parameters significantly weighed by the customer. Smooth ride and handling of the vehicle with exceptionally reliable wheel end solution is a paramount requirement in passenger Sports Utility Vehicle (SUV) vehicles subjected to challenging terrains and loads with rigid rear drive axle configuration. Traditional wheel-end bearing systems in passenger segment rigid rear drive axle utilizes the semi-floating layout, which imparts vertical bending loads and torsion to the axle shafts. The wheel-end bearing is usually a Single or Double Row Deep-Groove Ball Bearing (DRDGBB) or Double Row Angular Contact Ball Bearing (DRACBB). This solution is cost effective and simple in architecture. However, it lacks effectiveness against the heavy loads subjected to a SUV vehicle, especially the axial trust at high-speed cornering. This paper describes the solution of Double Row Taper Roller Bearing (DRTRB) wheel-end for a SUV vehicle in the rigid rear drive axle and improvement in terms of maximizing its load carrying capacity along with better reliability in terms of axial thrust in high-speed cornering. It describes the advantage of geometry of DRTRB over DRDGBB and DRACBB highlighting contact and load flow. The paper also highlights the vehicle level considerations affecting the B10 life of the bearing system for better selection of the DRTRB wheel-ends systems. This paper also describes real time vehicle level results along with theoretical improvements.

Keywords: axial thrust, b10 life, deep-groove ball bearing, taper roller bearing, semi-floating layout.

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Authors: Trishita Ray, Ashok Perka, Arnab Karani, M. Shome, Saurabh Kundu

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Line pipe steels are used for long distance transportation of crude oil and gas under extreme environmental conditions. Welding is necessary to lay large scale pipelines. Coarse Grain Heat Affected Zone (CGHAZ) of a welded joint exhibits worst toughness because of excessive grain growth and brittle microstructures like bainite and martensite, leading to early failure. Therefore, it is necessary to investigate microstructures and properties of the CGHAZ for different welding heat inputs. In the present study, CGHAZ for two heat inputs of 10 kJ/cm and 50 kJ/cm were simulated in Gleeble 3800, and the microstructures were investigated in detail by means of Scanning Electron Microscopy (SEM) and Electron Backscattered Diffraction (EBSD). Charpy Impact Tests were also done to evaluate the impact properties. High heat input was characterized with very low toughness and massive prior austenite grains. With the crystallographic information from EBSD, the area of a single prior austenite grain was traced out for both the welding conditions. Analysis of the prior austenite grains showed the formation of high angle boundaries between the crystallographic packets. Effect of these packet boundaries on secondary cleavage crack propagation was discussed. It was observed that in the low heat input condition, formation of finer packets with a criss-cross morphology inside prior austenite grains was effective in crack arrest whereas, in the high heat input condition, formation of larger packets with higher volume of low angle boundaries failed to resist crack propagation resulting in a brittle fracture. Thus, the characteristics in a crystallographic packet and impact properties are related and should be controlled to obtain optimum properties.

Keywords: coarse grain heat affected zone, crystallographic packet, toughness, line pipe steel

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Authors: Saurabh B. Ganorkar, Atul A. Shirkhedkar

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The need for investigations protecting against toxic impurities though seems to be a primary requirement; the impurities which may prove non - toxic can be explored for their therapeutic potential if any to assist advanced drug discovery. The essential role of pharmaceutical analysis can thus be extended effectively to achieve it. The present study successfully achieved these objectives with characterization of major degradation products as impurities for Zileuton which has been used for to treat asthma since years. The forced degradation studies were performed to identify the potential degradation products using Ultra-fine Liquid-chromatography. Liquid-chromatography-Mass spectrometry (Time of Flight) and Proton Nuclear Magnetic Resonance Studies were utilized effectively to characterize the drug along with five major oxidative and hydrolytic degradation products (DP’s). The mass fragments were identified for Zileuton and path for the degradation was investigated. The characterized DP’s were subjected to In-Silico studies as XP Molecular Docking to compare the gain or loss in binding affinity with 5-Lipooxygenase enzyme. One of the impurity of was found to have the binding affinity more than the drug itself indicating for its potential to be more bioactive as better Antiasthmatic. The close structural resemblance has the ability to potentiate or reduce bioactivity and or toxicity. The chances of being active biologically at other sites cannot be denied and the same is achieved to some extent by predictions for probability of being active with Prediction of Activity Spectrum for Substances (PASS) The impurities found to be bio-active as Antineoplastic, Antiallergic, and inhibitors of Complement Factor D. The toxicological abilities as Ames-Mutagenicity, Carcinogenicity, Developmental Toxicity and Skin Irritancy were evaluated using Toxicity Prediction by Komputer Assisted Technology (TOPKAT). Two of the impurities were found to be non-toxic as compared to original drug Zileuton. As the drugs are purposed and repurposed effectively the impurities can also be; as they can have more binding affinity; less toxicity and better ability to be bio-active at other biological targets.

Keywords: UFLC, LC-MS-TOF, NMR, Zileuton, impurities, toxicity, bio-activity

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Authors: Yogesh Rai, Saurabh Singh, Sanjay Pandey, Dhananjay K. Sah, B. G. Roy, B. S. Dwarakanath, Anant N. Bhatt

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One of the most common signatures of highly malignant gliomas is their capacity to metabolize more glucose to lactic acid than normal brain tissues, even under normoxic conditions (Warburg effect), indicating that aerobic glycolysis is constitutively upregulated through stable genetic or epigenetic changes. However, oxidative phosphorylation (OxPhos) is also required to maintain the mitochondrial membrane potential for tumor cell survival. In the process of tumorigenesis, tumor cells during fastest growth rate exhibit both high glycolytic and high OxPhos. Therefore, metabolically reprogrammed cancer cells with combination of both aerobic glycolysis and altered OxPhos develop a robust metabolic phenotype, which confers a selective growth advantage. In our study, we grew the high glycolytic BMG-1 (glioma) cells with continuous exposure of mitochondrial uncoupler 2, 4, dinitro phenol (DNP) for 10 passages to obtain a phenotype of high glycolysis with enhanced altered OxPhos. We found that OxPhos modified BMG (OPMBMG) cells has similar growth rate and cell cycle distribution but high mitochondrial mass and functional enzymatic activity than parental cells. In in-vitro studies, OPMBMG cells showed enhanced invasion, proliferation and migration properties. Moreover, it also showed enhanced angiogenesis in matrigel plug assay. Xenografted tumors from OPMBMG cells showed reduced latent period, faster growth rate and nearly five folds reduction in the tumor take in nude mice compared to BMG-1 cells, suggesting that robust metabolic phenotype facilitates tumor formation and growth. OPMBMG cells which were found radio-resistant, showed enhanced radio-sensitization by 2-DG as compared to the parental BMG-1 cells. This study suggests that metabolic reprogramming in cancer cells enhances the potential of migration, invasion and proliferation. It also strengthens the cancer cells to escape the death processes, conferring resistance to therapeutic modalities. Our data also suggest that combining metabolic inhibitors like 2-DG with conventional therapeutic modalities can sensitize such metabolically aggressive cancer cells more than the therapies alone.

Keywords: 2-DG, BMG, DNP, OPM-BMG

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Authors: Kaushal Kishore, Vaibhav Jain, Hrishikesh Jugade, Saurabh Hadas, Manashi Adhikary, Goutam Mukhopadhyay, Sandip Bhattacharyya

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Rotary air compressors in air conditioners are used to suck excessive volume of air from the atmosphere in a small space to provide drive to the components attached to them. Hydraulic test is one of the most important methods to decide the suitability of these components for usage. In the present application, projection welding is used to join the hot rolled steel sheets after forming for manufacturing of air compressors. These sheets belong to two different high strength low alloy (HSLA) steel grades. It was observed that one batch of compressors made of a particular grade was cracking from the weld, whereas those made of another grade were passing the hydraulic tests. Cracking was repeatedly observed from the weld location. A detailed comparative study of the compressors which failed and successfully passed pressure tests has been presented. Location of crack initiation was identified to be the interface of fusion zone/heat affected zone. Shear dimples were observed on the fracture surface confirming the ductile mode of failure. Hardness profile across the weld revealed a sharp rise in hardness in the fusion zone. This was attributed to the presence of untempered martensitic lath in the fusion zone. A sharp metallurgical notch existed at the heat affected zone/fusion zone interface due to transition in microstructure from acicular ferrite and bainite in HAZ to untempered martensite in the fusion zone. In contrast, welds which did not fail during the pressure tests showed a smooth hardness profile with no abnormal rise in hardness in the fusion zone. The bainitic microstructure was observed in the fusion zone of successful welds. This difference in microstructural constituents in the fusion zone was attributed to the presence of a small amount of boron (0.002 wt. %) in the sheets which were cracking. Trace amount of boron is known to substantially increase the hardenability of HSLA steel, and cooling rate during resolidification in the fusion zone is sufficient to form martensite. Post-weld heat treatment was recommended to transform untempered martensite to tempered martensite with lower hardness.

Keywords: compressor, cracking, martensite, weld, boron, hardenability, high strength low alloy steel

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Authors: Prince Kumar, Shamseer Kulangara Kandi, Diwan S. Rawat, Kasturi Mukhopadhyay

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Staphylococcus aureus is the most pathogenic of all staphylococci, a major cause of nosocomial infections, and known for acquiring resistance towards various commonly used antibiotics. Due to the widespread use of synthetic drugs, clinicians are now facing a serious threat in healthcare. The increasing resistance in staphylococci has created a need for alternatives to these synthetic drugs. One of the alternatives is a natural plant-based medicine for both disease prevention as well as the treatment of chronic diseases. Among such natural compounds, curcumin is one of the most studied molecules and has been an integral part of traditional medicines and Ayurveda from ancient times. It is a natural polyphenolic compound with diverse pharmacological effects, including anti-inflammatory, antioxidant, anti-cancerous and antibacterial activities. In spite of its efficacy and potential, curcumin has not been approved as a therapeutic agent yet, because of its low solubility, low bioavailability, and rapid metabolism in vivo. The presence of central β-diketone moiety in curcumin is responsible for its rapid metabolism. To overcome this, in the present study, curcuminoids were designed by modifying the central β-diketone moiety of curcumin into mono carbonyl moiety and their antibacterial potency against S. aureus ATCC 29213 was determined. Further, the mode of action and hemolytic activity of the most potent curcuminoids were studied. Minimum inhibitory concentration (MIC) and in vitro killing kinetics were used to study the antibacterial activity of the designed curcuminoids. For hemolytic assay, mouse Red blood cells were incubated with curcuminoids and hemoglobin release was measured spectrophotometrically. The mode of action of curcuminoids was analysed by membrane depolarization assay using membrane potential sensitive dye 3,3’-dipropylthiacarbocyanine iodide (DiSC3(5)) through spectrofluorimetry and membrane permeabilization assay using calcein-AM through flow cytometry. Antibacterial screening of the designed library (61 curcuminoids) revealed excellent in vitro potency of six compounds against S. aureus (MIC 8 to 32 µg/ml). Moreover, these six compounds were found to be non-hemolytic up to 225 µg/ml that is much higher than their corresponding MIC values. The in vitro killing kinetics data showed five of these lead compounds to be bactericidal causing >3 log reduction in the viable cell count within 4 hrs at 5 × MIC while the sixth compound was found to be bacteriostatic. Depolarization assay revealed that all the six curcuminoids caused depolarization in their corresponding MIC range. Further, the membrane permeabilization assay showed that all the six curcuminoids caused permeabilization at 5 × MIC in 2 hrs. This membrane depolarization and permeabilization caused by curcuminoids found to be in correlation with their corresponding killing efficacy. Both these assays point out that membrane perturbations might be a primary mode of action for these curcuminoids. Overall, the present study leads us six water soluble, non-hemolytic, membrane-active curcuminoids and provided an impetus for further research on therapeutic use of these lead curcuminoids against S. aureus.

Keywords: antibacterial, curcumin, minimum inhibitory concentration , Staphylococcus aureus

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Authors: Sunita Boro, Saurabh Kumar Dixit

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Terroir, an intricate fusion of geography, climate, soil, and human expertise, has long been acknowledged as a defining factor in the character of wines and foods. This research embarks on an exploration of terroir's profound influence on gastronomic tourism, shedding light on the intricate interplay between the physical environment and culinary artistry. Delving into the intricate science of terroir, we scrutinize its role in shaping the sensory profiles of wines and foods, emphasizing the profound impact of specific regions on flavor, aroma, and texture. We deploy a multifaceted methodology, amalgamating sensory analysis, chemical profiling, geographical information systems, and qualitative interviews to unearth the nuanced nuances of terroir expression. Through an exhaustive review of the literature, we elucidate the historical roots of terroir, unveil the intricate cultural dimensions shaping it, and provide a comprehensive examination of prior studies in the field. Our findings underscore the pivotal role of terroir in promoting regional identities, enhancing the economic viability of locales, and attracting gastronomic tourists. The paper also dissects the marketing strategies employed to promote terroir-driven food and wine experiences. We elucidate the utilization of storytelling, branding, and collaborative endeavors in fostering a robust terroir-based tourism industry. This elucidates both the potential for innovation and the challenges posed by oversimplification or misrepresentation of terroir. Our research spotlights the intersection of terroir and sustainability, emphasizing the significance of environmentally conscious practices in terroir-driven productions. We discern the harmonious relationship between sustainable agriculture, terroir preservation, and responsible tourism, encapsulating the essence of ecological integrity in gastronomic tourism. Incorporating compelling case studies of regions and businesses excelling in the terroir-based tourism realm, we offer in-depth insights into successful models and strategies, with an emphasis on their replicability and adaptability to various contexts. Ultimately, this paper not only contributes to the scholarly understanding of terroir's role in the world of food and wine tourism but also provides actionable recommendations for stakeholders to leverage terroir's allure, preserve its authenticity, and foster sustainable and enriching culinary tourism experiences.

Keywords: terroir, food tourism, wine tourism, sustainability

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Authors: Varun Joshi, M. S. Rawat

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The Indian Himalayan Region (IHR) is inherently fragile and susceptible to landslide hazard due to its extremely weak geology, highly rugged topography and heavy monsoonal rainfall. One of the most common hazards in the IHR is landslide, and this event is particularly frequent in Himalayan states of India i.e. Jammu & Kashmir, Himachal Pradesh, Uttarakhand, Sikkim, Manipur and Arunachal Pradesh. Landslides are mostly triggered by extreme rainfall events but the incidence increases during monsoon months (June to September). Natural slopes which are otherwise stable but they get destabilized due to anthropogenic activities like construction of various developmental activities and deforestation. These activities are required to fulfill the developmental needs and upliftment of societal status in the region. Landslides also trigger during major earthquakes and reported most observable and damaging phenomena. Studies indicate that the landslide phenomenon has increased many folds due to developmental activities in Himalayan region. Gradually increasing and devastating consequences of landslides turned into one of the most important hydro-geological hazards in Himalayan states especially in Uttarakhand and Sikkim states of India. The recent most catastrophic rainfall in June 2013 in Uttarakhand lead to colossal loss of life and property. The societal damage due to this incident is still to be recovered even after three years. Sikkim earthquake of September 2011 is witnessed for triggering of large number of coseismic landslides. The rescue and relief team faced huge problem in helping the trapped villagers in remote locations of the state due to road side blockade by landslides. The recent past incidences of landslides in Uttarakhand, as well as Sikkim states, created a new domain of research in terms of understanding the phenomena of landslide and management of disaster in such situation. Every year at many locations landslides trigger which force dwellers to either evacuate their dwelling or lose their life and property. The communication and transportation networks are also severely affected by landslides at several locations. Many times the drinking water supply disturbed and shortage of daily need household items reported during monsoon months. To minimize the severity of landslide in IHR requires in-depth research and developmental planning. For most of the areas in the present study, landslide hazard zonation is done on 1:50,000 scale. The land use planning maps on extensive basis are not available. Therefore, there is a need of large-scale landslide hazard zonation and land use planning maps. If the scientist conduct research on desired aspects and their outcome of research is utilized by the government in developmental planning then the incidents of landslide could be minimized, subsequent impact on society, life and property would be reduced. Along with the scientific research, there is another need of awareness generation in the region for stake holders and local dwellers to combat with the landslide hazard, if triggered in their location.

Keywords: coseismic, Indian Himalayan Region, landslide hazard zonation, Sikkim, societal, Uttarakhand

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Authors: Sunil Chandra, Himanshu Rawat, Vikas Gusain, Triparna Barman

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Forest fires are a recurrent phenomenon in the Himalayan region owing to the presence of vulnerable forest types, topographical gradients, climatic weather conditions, and anthropogenic pressure. The present study focuses on the identification of forest fire-affected areas in a small part of the West Himalayan region using a differential normalized burnt ratio method and spectral unmixing methods. The study area has a rugged terrain with the presence of sub-tropical pine forest, montane temperate forest, and sub-alpine forest and scrub. The major reason for fires in this region is anthropogenic in nature, with the practice of human-induced fires for getting fresh leaves, scaring wild animals to protect agricultural crops, grazing practices within reserved forests, and igniting fires for cooking and other reasons. The fires caused by the above reasons affect a large area on the ground, necessitating its precise estimation for further management and policy making. In the present study, two approaches have been used for carrying out a burnt area analysis. The first approach followed for burnt area analysis uses a differenced normalized burnt ratio (dNBR) index approach that uses the burnt ratio values generated using the Short-Wave Infrared (SWIR) band and Near Infrared (NIR) bands of the Sentinel-2 image. The results of the dNBR have been compared with the outputs of the spectral mixing methods. It has been found that the dNBR is able to create good results in fire-affected areas having homogenous forest stratum and with slope degree <5 degrees. However, in a rugged terrain where the landscape is largely influenced by the topographical variations, vegetation types, tree density, the results may be largely influenced by the effects of topography, complexity in tree composition, fuel load composition, and soil moisture. Hence, such variations in the factors influencing burnt area assessment may not be effectively carried out using a dNBR approach which is commonly followed for burnt area assessment over a large area. Hence, another approach that has been attempted in the present study utilizes a spectral mixing method where the individual pixel is tested before assigning an information class to it. The method uses a neural network approach utilizing Sentinel-2 bands. The training and testing data are generated from the Sentinel-2 data and the national field inventory, which is further used for generating outputs using ML tools. The analysis of the results indicates that the fire-affected regions and their severity can be better estimated using spectral unmixing methods, which have the capability to resolve the noise in the data and can classify the individual pixel to the precise burnt/unburnt class.

Keywords: categorical data, log linear modeling, neural network, shifting cultivation

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Authors: Saurabh Sharma, Yong Sun, Bruce Vernham

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Accurate prediction of NOx emission is a continuous challenge in the field of diesel engine-out emission modeling. Performing experiments for each conditions and scenario cost significant amount of money and man hours, therefore model-based development strategy has been implemented in order to solve that issue. NOx formation is highly dependent on the burn gas temperature and the O₂ concentration inside the cylinder. The current empirical models are developed by calibrating the parameters representing the engine operating conditions with respect to the measured NOx. This makes the prediction of purely empirical models limited to the region where it has been calibrated. An alternative solution to that is presented in this paper, which focus on the utilization of in-cylinder combustion parameters to form a predictive semi-empirical NOx model. The result of this work is shown by developing a fast and predictive NOx model by using the physical parameters and empirical correlation. The model is developed based on the steady state data collected at entire operating region of the engine and the predictive combustion model, which is developed in Gamma Technology (GT)-Power by using Direct Injected (DI)-Pulse combustion object. In this approach, temperature in both burned and unburnt zone is considered during the combustion period i.e. from Intake Valve Closing (IVC) to Exhaust Valve Opening (EVO). Also, the oxygen concentration consumed in burnt zone and trapped fuel mass is also considered while developing the reported model.  Several statistical methods are used to construct the model, including individual machine learning methods and ensemble machine learning methods. A detailed validation of the model on multiple diesel engines is reported in this work. Substantial numbers of cases are tested for different engine configurations over a large span of speed and load points. Different sweeps of operating conditions such as Exhaust Gas Recirculation (EGR), injection timing and Variable Valve Timing (VVT) are also considered for the validation. Model shows a very good predictability and robustness at both sea level and altitude condition with different ambient conditions. The various advantages such as high accuracy and robustness at different operating conditions, low computational time and lower number of data points requires for the calibration establishes the platform where the model-based approach can be used for the engine calibration and development process. Moreover, the focus of this work is towards establishing a framework for the future model development for other various targets such as soot, Combustion Noise Level (CNL), NO₂/NOx ratio etc.

Keywords: diesel engine, machine learning, NOₓ emission, semi-empirical

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Authors: Rabbia Idrees, Ananda Maiti, Saurabh Garg, Muhammad Bilal Amin

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IoT devices are the basic building blocks of IoT network that generate enormous volume of real-time and high-speed data to help organizations and companies to take intelligent decisions. To integrate this enormous data from multisource and transfer it to the appropriate client is the fundamental of IoT development. The handling of this huge quantity of devices along with the huge volume of data is very challenging. The IoT devices are battery-powered and resource-constrained and to provide energy efficient communication, these IoT devices go sleep or online/wakeup periodically and a-periodically depending on the traffic loads to reduce energy consumption. Sometime these devices get disconnected due to device battery depletion. If the node is not available in the network, then the IoT network provides incomplete, missing, and inaccurate data. Moreover, many IoT applications, like vehicle tracking and patient tracking require the IoT devices to be mobile. Due to this mobility, If the distance of the device from the sink node become greater than required, the connection is lost. Due to this disconnection other devices join the network for replacing the broken-down and left devices. This make IoT devices dynamic in nature which brings uncertainty and unreliability in the IoT network and hence produce bad quality of data. Due to this dynamic nature of IoT devices we do not know the actual reason of abnormal data. If data are of poor-quality decisions are likely to be unsound. It is highly important to process data and estimate data quality before bringing it to use in IoT applications. In the past many researchers tried to estimate data quality and provided several Machine Learning (ML), stochastic and statistical methods to perform analysis on stored data in the data processing layer, without focusing the challenges and issues arises from the dynamic nature of IoT devices and how it is impacting data quality. A comprehensive review on determining the impact of dynamic nature of IoT devices on data quality is done in this research and presented a data quality model that can deal with this challenge and produce good quality of data. This research presents the data quality model for the sensors monitoring water quality. DBSCAN clustering and weather sensors are used in this research to make data quality model for the sensors monitoring water quality. An extensive study has been done in this research on finding the relationship between the data of weather sensors and sensors monitoring water quality of the lakes and beaches. The detailed theoretical analysis has been presented in this research mentioning correlation between independent data streams of the two sets of sensors. With the help of the analysis and DBSCAN, a data quality model is prepared. This model encompasses five dimensions of data quality: outliers’ detection and removal, completeness, patterns of missing values and checks the accuracy of the data with the help of cluster’s position. At the end, the statistical analysis has been done on the clusters formed as the result of DBSCAN, and consistency is evaluated through Coefficient of Variation (CoV).

Keywords: clustering, data quality, DBSCAN, and Internet of things (IoT)

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Authors: Saurabh Sharma

Abstract:

Introduction: The case study deals with the ground stabilisation of Nabi Karim Metro Station in Delhi, India, wherein an extremely complex geology was encountered while excavating the tunnelling shaft for launching Tunnel Boring Machine. The borelog investigation and the Seismic Refraction Technique (SRT) indicated towards the presence of an extremely hard rocky mass from a depth of 3-4 m itself, and accordingly, the Geotechnical Interpretation Report (GIR) concluded the presence of Grade-IV rock from 3m onwards and presence of Grade-III and better rock from 5-6m onwards. Accordingly, it was planned to retain the ground by providing secant piles all around the launching shaft and then excavating the shaft vertically after leaving a berm of 1.5m to prevent secant piles from getting exposed. To retain the side slopes, rock bolting with shotcreting and wire meshing were proposed, which is a normal practice in such strata. However, with the increase in depth of excavation, the rock quality kept on decreasing at an unexpected and surprising pace, with the Grade-III rock mass at 5-6 m converting to conglomerate formation at the depth of 15m. This worsening of geology from high grade rock to slushy conglomerate formation can never be predicted and came as a surprise to even the best geotechnical engineers. Since the excavation had already been cut down vertically to manage the shaft size, the execution was continued with enhanced cautions to stabilise the side slopes. But, when the shaft work was about to finish, a collapse was encountered on one side of the excavation shaft. This collapse was unexpected and surprising since all measures to stabilise the side slopes had been taken after face mapping, and the grid size, diameter, and depth of the rockbolts had already been readjusted to accommodate rock fractures. The above scenario was baffling even to the best geologists and geotechnical engineers, and it was decided that any further slope stabilisation scheme shall have to be designed in such a way to ensure safe completion of works. Accordingly, following revisions to excavation scheme were made: The excavation would be carried while maintaining a slope based on type of soil/rock. The rock bolt type was changed from SN rockbolts to Self Drilling type anchor. The grid size of the bolts changed on real time assessment. the excavation carried out by implementing a ‘Bench Release Approach’. Aggressive Real Time Instrumentation Scheme. Discussion: The above case Study again asserts vitality of correct interpretation of the geological strata and the need of real time revisions of the construction schemes based on the actual site data. The excavation is successfully being done with the above revised scheme, and further details of the Revised Slope Stabilisation Scheme, Instrumentation Schemes, Monitoring results, along with the actual site photographs, shall form the part of the final Paper.

Keywords: unconfined compressive strength (ucs), rock mass rating (rmr), rock bolts, self drilling anchors, face mapping of rock, secant pile, shotcrete

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Authors: Reshma Raskar-Phule, Makarand Landge, Saurabh Singh, Vijay Singh, Jash Saparia, Shivam Tripathi

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For any construction project, slope calculations are necessary in order to evaluate constructability on the site, such as the slope of parking lots, sidewalks, and ramps, the slope of sanitary sewer lines, slope of roads and highways. When slopes and grades are to be determined, designers are concerned with establishing proper slopes and grades for their projects to assess cut and fill volume calculations and determine inverts of pipes. There are several established instruments commonly used to determine slopes, such as Dumpy level, Abney level or Hand Level, Inclinometer, Tacheometer, Henry method, etc., and surveyors are very familiar with the use of these instruments to calculate slopes. However, they have some other drawbacks which cannot be neglected while major surveying works. Firstly, it requires expert surveyors and skilled staff. The accessibility, visibility, and accommodation to remote hilly terrain with these instruments and surveying teams are difficult. Also, determination of gentle slopes in case of road and sewer drainage constructions in congested urban places with these instruments is not easy. This paper aims to develop a method that requires minimum field work, minimum instruments, no high-end technology or instruments or software, and low cost. It requires basic and handy surveying accessories like a plane table with a fixed weighing machine, standard weights, alidade, tripod, and ranging rods should be able to determine the terrain slope in congested areas as well as in remote hilly terrain. Also, being simple and easy to understand and perform the people of that local rural area can be easily trained for the proposed method. The idea for the proposed method is based on the principle of resolution of weight components. When any object of standard weight ‘W’ is placed on an inclined surface with a weighing machine below it, then its cosine component of weight is presently measured by that weighing machine. The slope can be determined from the relation between the true or actual weight and the apparent weight. A proper procedure is to be followed, which includes site location, centering and sighting work, fixing the whole set at the identified station, and finally taking the readings. A set of experiments for slope determination, mild and moderate slopes, are carried out by the proposed method and by the theodolite instrument in a controlled environment, on the college campus, and uncontrolled environment actual site. The slopes determined by the proposed method were compared with those determined by the established instruments. For example, it was observed that for the same distances for mild slope, the difference in the slope obtained by the proposed method and by the established method ranges from 4’ for a distance of 8m to 2o15’20” for a distance of 16m for an uncontrolled environment. Thus, for mild slopes, the proposed method is suitable for a distance of 8m to 10m. The correlation between the proposed method and the established method shows a good correlation of 0.91 to 0.99 for various combinations, mild and moderate slope, with the controlled and uncontrolled environment.

Keywords: surveying, plane table, weight component, slope determination, hilly terrain, construction

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Authors: Kuldeep Rawat, Michael O'Shea, Maureen McGough

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The paper will discuss a National Institute of Justice (NIJ) funded project to provide cost-effective aviation technologies and research to support counter-poaching operations related to endangered, protected, and/or regulated wildlife. The goal of this project is to provide cost-effective aviation technology and research support to Kenya Wildlife Service (KWS) in their counter-poaching efforts. In pursuit of this goal, Elizabeth City State University (ECSU) is assisting the National Institute of Justice (NIJ) in enhancing the Kenya Wildlife Service’s aviation technology and related capacity to meet its counter-poaching mission. Poaching, at its core, is systemic as poachers go to the most extreme lengths to kill high target species such as elephant and rhino. These high target wildlife species live in underdeveloped or impoverished nations, where poachers find fewer barriers to their operations. In Kenya, with fifty-nine (59) parks and reserves, spread over an area of 225,830 square miles (584,897 square kilometers) adequate surveillance on the ground is next to impossible. Cost-effective aviation surveillance technologies, based on a comprehensive needs assessment and operational evaluation, are needed to curb poaching and effectively prevent wildlife trafficking. As one of the premier law enforcement Air Wings in East Africa, KWS plays a crucial role in Kenya, not only in counter-poaching and wildlife conservation efforts, but in aerial surveillance, counterterrorism and national security efforts as well. While the Air Wing has done, a remarkable job conducting aerial patrols with limited resources, additional aircraft and upgraded technology should significantly advance the Air Wing’s ability to achieve its wildlife protection mission. The project includes: (i) Needs Assessment of the KWS Air Wing, to include the identification of resources, current and prospective capacity, operational challenges and priority goals for expansion, (ii) Acquisition of Low-Cost Aviation Technology to meet priority needs, and (iii) Operational Evaluation of technology performance, with a focus on implementation and effectiveness. The Needs Assessment reflects the priorities identified through two site visits to the KWS Air Wing in Nairobi, Kenya, as well as field visits to multiple national parks receiving aerial support and interviewing/surveying KWS Air wing pilots and leadership. Needs Assessment identified some immediate technology needs that includes, GPS with upgrades, including weather application, Night flying capabilities, to include runway lights and night vision technology, Cameras and surveillance equipment, Flight tracking system and/or Emergency Position Indicating Radio Beacon, Lightweight ballistic-resistant body armor, and medical equipment, to include a customized stretcher and standard medical evacuation equipment. Results of this assessment, along with significant input from the KWS Air Wing, will guide the second phase of this project: technology acquisition. Acquired technology will then be evaluated in the field, with a focus on implementation and effectiveness. Results will ultimately be translated for any rural or tribal law enforcement agencies with comparable aerial surveillance missions and operational environments, and jurisdictional challenges, seeking to implement low-cost aviation technology. Results from Needs Assessment phase, including survey results and our ongoing technology acquisition and baseline operational evaluation will be discussed in the paper.

Keywords: aerial surveillance mission, aviation technology, counter-poaching, wildlife protection

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Authors: Aastha Arora, Vikas Bhuria, Saurabh Singh, Uma Pathak, Shweta Mathur, Puja P. Hazari, Rajat Sandhir, Ravi Soni, Anant N. Bhatt, Bilikere S. Dwarakanath

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Radiotherapy is an effective curative and palliative option for patients with thoracic malignancies. However, lung injury, comprising of pneumonitis and fibrosis, remains a significant clin¬ical complication of thoracic radiation, thus making it a dose-limiting factor. Also, injury to the lung is often reported as part of multi-organ failure in victims of accidental radiation exposures. Radiation induced inflammatory response in the lung, characterized by leukocyte infiltration and vascular changes, is an important contributing factor for the injury. Therefore, countermeasure agents to attenuate radiation induced inflammatory response are considered as an important approach to prevent chronic lung damage. Although Amifostine, the widely used, FDA approved radio-protector, has been found to reduce the radiation induced pneumonitis during radiation therapy of non-small cell lung carcinoma, its application during mass and field exposure is limited due to associated toxicity and ineffectiveness with the oral administration. The amifostine analogue (DRDE-30) overcomes this limitation as it is orally effective in reducing the mortality of whole body irradiated mice. The current study was undertaken to investigate the potential of DRDE-30 to ameliorate radiation induced lung damage. DRDE-30 was administered intra-peritoneally, 30 minutes prior to 13.5 Gy thoracic (60Co-gamma) radiation in C57BL/6 mice. Broncheo- alveolar lavage fluid (BALF) and lung tissues were harvested at 12 and 24 weeks post irradiation for studying inflammatory and fibrotic markers. Lactate dehydrogenase (LDH) leakage, leukocyte count and protein content in BALF were used as parameters to evaluate lung vascular permeability. Inflammatory cell signaling (p38 phosphorylation) and anti-oxidant status (MnSOD and Catalase level) was assessed by Western blot, while X-ray CT scan, H & E staining and trichrome staining were done to study the lung architecture and collagen deposition. Irradiation of the lung increased the total protein content, LDH leakage and total leukocyte count in the BALF, reflecting endothelial barrier dysfunction. These disruptive effects were significantly abolished by DRDE-30, which appear to be linked to the DRDE-30 mediated abrogation of activation of the redox-sensitive pro- inflammatory signaling cascade, the MAPK pathway. Concurrent administration of DRDE-30 with radiation inhibited radiation-induced oxidative stress by strengthening the anti-oxidant defense system and abrogated p38 mitogen-activated protein kinase activation, which was associated with reduced vascular leak and macrophage recruitment to the lungs. Histopathological examination (by H & E staining) of the lung showed radiation-induced inflammation of the lungs, characterized by cellular infiltration, interstitial oedema, alveolar wall thickening, perivascular fibrosis and obstruction of alveolar spaces, which were all reduced by pre-administration of DRDE-30. Structural analysis with X-ray CT indicated lung architecture (linked to the degree of opacity) comparable to un-irradiated mice that correlated well with the lung morphology and reduced collagen deposition. Reduction in the radiation-induced inflammation and fibrosis brought about by DRDE-30 resulted in a profound increase in animal survival (72 % in the combination vs 24% with radiation) observed at the end of 24 weeks following irradiation. These findings establish the potential of the Amifostine analogue, DRDE-30, in reducing radiation induced pulmonary injury by attenuating the inflammatory and fibrotic responses.

Keywords: amifostine, fibrosis, inflammation, lung injury radiation

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