Search results for: Vikas Upadhyay

Authors: Dileep G., Akash Singh, Dalchand Ahirwar, Arkadeep Ghosh, Ashutosh Purohit, Gaurav Guleria, Kshatriya Om Prashant, Pushkar Patel, Saksham Kumar, Vanshaj Nathani, Vikas Dangi, Shubhajit Roy Chowdhury, Varun Dutt

Abstract:

Transcranial direct current stimulation (tDCS) has shown promise as a novel approach to enhance cognitive performance and provide therapeutic benefits for various brain disorders. However, the exact underlying brain mechanisms are not fully understood. We conducted a study to examine the brain's functional changes when subjected to simultaneous tDCS and music (Indian classical raga). During the study, participants in the experimental group underwent a 20-minute session of tDCS at two mA while listening to music (raga) for a duration of seven days. In contrast, the control group received a sham stimulation for two minutes at two mA over the same seven-day period. The objective was to examine whether repetitive tDCS could lead to the formation of additional functional connections between the medial prefrontal cortex (the stimulated area) and the auditory cortex in comparison to a sham stimulation group. In this study, 26 participants (5 female) underwent pre- and post-intervention scans, where changes were compared after one week of either tDCS or sham stimulation in conjunction with music. The study revealed significant effects of tDCS on functional connectivity between the stimulated area and the auditory cortex. The combination of tDCS applied over the mPFC and music resulted in newly formed connections. Based on our findings, it can be inferred that applying anodal tDCS over the mPFC enhances functional connectivity between the stimulated area and the auditory cortex when compared to the effects observed with sham stimulation.

Keywords: fNIRS, tDCS, neuroplasticity, music

Procedia PDF Downloads 36

Authors: Garg Ramneesh, Uppal Sanjeev, Mittal Rajinder, Shah Sheerin, Jain Vikas, Singla Bhupinder

Abstract:

Introduction: Despite advances in trauma care, a classification system for soft tissue injuries of the face still needs to be objectively defined. Aim: To develop a classification system for soft tissue injuries of the face; that is objective, easy to remember, reproducible, universally applicable, aids in surgical management and helps to develop a structured data that can be used for future use. Material and Methods: This classification system includes those patients that need surgical management of facial injuries. Associated underlying bony fractures have been intentionally excluded. Depending upon the severity of soft tissue injury, these can be graded from 0 to IV (O-Abrasions, I-lacerations, II-Avulsion injuries with no skin loss, III-Avulsion injuries with skin loss that would need graft or flap cover, and IV-complex injuries). Anatomically, the face has been divided into three zones (Zone 1/2/3), as per aesthetic subunits. Zone 1e stands for injury of eyebrows; Zones 2 a/b/c stand for nose, upper eyelid and lower eyelid respectively; Zones 3 a/b/c stand for upper lip, lower lip and cheek respectively. Suffices R and L stand for right or left involved side, B for presence of foreign body like glass or pellets, C for extensive contamination and D for depth which can be graded as D 1/2/3 if depth is still fat, muscle or bone respectively. I is for damage to facial nerve or parotid duct. Results and conclusions: This classification system is easy to remember, clinically applicable and would help in standardization of surgical management of soft tissue injuries of face. Certain inherent limitations of this classification system are inability to classify sutured wounds, hematomas and injuries along or against Langer’s lines.

Keywords: soft tissue injuries, face, avulsion, classification

Procedia PDF Downloads 356

Authors: Suraj Amrutkar, R. Gowri, Asma Khan, Nazam Khan, Vikas Mahajan, Manpreet Kour And Bharti Deshmukh

Abstract:

Herbal additives are rich in vitamin C, A and other biological active compounds and may act as surrogate source to subdue heat stress in chicken. Among various herbal additives such as rough lemon (Citrus Jambhiri Lush) juice, amla (Emblica officinalis) juice and aloe vera (Aloe barbadensis miller) gel are easily available during summer (stress period) and also cost less as comparison to synthetic feed additives in market. In order to analyze the performance by supplementation of rough lemon juice, amla juice and aloe vera gel in broiler under heat stress conditions. Study was carried out with a random distribution of day old straight run chicks (240 No.) in to four treatment group (n=60) was done. All the groups were given basal diet (Maize-Soya based; T0) was same for all the groups with supplementation of rough lemon juice (T1), amla juice (T2) and aloe vera (T3) @ 2% in drinking water. Experiment trial lasted for 42 days during heat stress period (June-July) with minimum THI (78.2) and Maximum THI (88.02). Feed and water were offered ad-libitum throughout the trial. Results revealed significantly higher (P<0.05) body weight in T3 and T2, followed by T1 and least in T0 at 42 days of age. The overall mean of Feed conversion ratio of various treatment T0, T1, T2 andT3 were 2.16, 1.98, 1.89 and 1.82, respectively. The mortality percentage in various treatment, T0, T1, T2 and T3, were 6.67, 3.33, 0.0 and 1.67, respectively. pH value, PCV (%), Sodium (mmol/L) and Potassium (mmol/L) was higher in T3 than rest of the groups. HL ratio is significantly lower (P<0.05) in T3, T2 followed by T1 than T0 at 42 days of age. It may be inferred that amongst these phyto-additives, aloe vera leads in alleviating heat stress in broiler in an economical way, followed by amla and rough lemon.

Keywords: rough lemon, amla, aloe vera, heat stress, broiler

Procedia PDF Downloads 51

Authors: Gaurav D. Sonawane, Vikas G. Sargade

Abstract:

The present investigation is a study of the effect of advanced Physical Vapor Deposition (PVD) coatings on cutting temperature residual stresses and surface roughness during Duplex Stainless Steel (DSS) 2205 turning. Austenite stabilizers like nickel, manganese, and molybdenum reduced the cost of DSS. Surface Integrity (SI) plays an important role in determining corrosion resistance and fatigue life. Resistance to various types of corrosion makes DSS suitable for applications with critical environments like Heat exchangers, Desalination plants, Seawater pipes and Marine components. However, lower thermal conductivity, poor chip control and non-uniform tool wear make DSS very difficult to machine. Cemented carbide tools (M grade) were used to turn DSS in a dry environment. AlTiN and AlTiCrN coatings were deposited using advanced PVD High Pulse Impulse Magnetron Sputtering (HiPIMS) technique. Experiments were conducted with cutting speed of 100 m/min, 140 m/min and 180 m/min. A constant feed and depth of cut of 0.18 mm/rev and 0.8 mm were used, respectively. AlTiCrN coated tools followed by AlTiN coated tools outperformed uncoated tools due to properties like lower thermal conductivity, higher adhesion strength and hardness. Residual stresses were found to be compressive for all the tools used for dry turning, increasing the fatigue life of the machined component. Higher cutting temperatures were observed for coated tools due to its lower thermal conductivity, which results in very less tool wear than uncoated tools. Surface roughness with uncoated tools was found to be three times higher than coated tools due to lower coefficient of friction of coating used.

Keywords: cutting temperature, DSS2205, dry turning, HiPIMS, surface integrity

Procedia PDF Downloads 98

Authors: Yongjiang Zhang, Kallol Barai, Umesh R. Hodeghatta, Trang Tran, Vikas Dhiman

Abstract:

Detecting water stress on crops early and accurately is crucial to minimize its impact. This study aims to measure water stress in wild blueberry crops non-destructively by analyzing proximal hyperspectral data. The data collection took place in the summer growing season of 2022. A drought experiment was conducted on wild blueberries in the randomized block design in the greenhouse, incorporating various genotypes and irrigation treatments. Hyperspectral data ( spectral range: 400-1000 nm) using a handheld spectroradiometer and leaf water potential data using a pressure chamber were collected from wild blueberry plants. Machine learning techniques, including multiple regression analysis and random forest models, were employed to predict leaf water potential (MPa). We explored the optimal wavelength bands for simple differences (RY1-R Y2), simple ratios (RY1/RY2), and normalized differences (|RY1-R Y2|/ (RY1-R Y2)). NDWI ((R857 - R1241)/(R857 + R1241)), SD (R2188 – R2245), and SR (R1752 / R1756) emerged as top predictors for predicting leaf water potential, significantly contributing to the highest model performance. The base learner models achieved an R-squared value of approximately 0.81, indicating their capacity to explain 81% of the variance. Research is underway to develop a neural vegetation index (NVI) that automates the process of index development by searching for specific wavelengths in the space ratio of linear functions of reflectance. The NVI framework could work across species and predict different physiological parameters.

Keywords: hyperspectral reflectance, water potential, spectral indices, machine learning, wild blueberries, optimal bands

Procedia PDF Downloads 37

Authors: Sobhy A. El-Sohaimy, Mohamed G. Shehata, Ashwani Mathur, Amira G. Darwish, Nourhan M. Abd El-Aziz, Pammi Gauba, Pooja Upadhyay

Abstract:

Sea buckthorn is a temperate bush plant native to Asian and European countries, explored across the world in traditional medicine to treat various diseases due to the presence of an exceptionally high content of phenolics, flavonoids and antioxidants. In addition to the evaluation of nutrients and active compounds, the focus of the present work was to assess the optimal levels for L. plantarum RM1 growth by applying response surface methodology (RSM), and to determine the impact of juice fermentation on antioxidant, anti-hypertension and anticancer activity, as well as on organoleptic properties. Sea buckthorn berries were shown to contain good fiber content (6.55%, 25 DV%), high quality of protein (3.12%, 6.24 DV%) containing: histidine, valine, threonine, leucine and lysine (with AAS 24.32, 23.66, 23.09, 23.05 and 21.71%, respectively), and 4.45% sugar that pro- vides only 79 calories. Potassium was shown to be the abundant mineral content (793.43%, 22.66 DV), followed by copper and phosphorus (21.81 and 11.07 DV%, respectively). Sea buckthorn juice exhibited a rich phenolic, flavonoid and carotenoid content (283.58, 118.42 and 6.5 mg/g, respec- tively), in addition to a high content of vitamin C (322.33 mg/g). The HPLC profile indicated that benzoic acid is the dominant phenolic compound in sea buckthorn berries (3825.90 mg/kg). Antiox- idant potentials (DPPH and ABTS) of sea buckthorn showed higher inhibition than ascorbic acid. Antimicrobial potentials were most pronounced against Escherichia coli BA12296 (17.46 mm). The probiotic growth was 8.5 log cfu/mL, with juice concentration, inoculum size and temperature as the main contributors to probiotic growth with a 95% confidence level. Fermentation of sea buck- thorn juice with L. plantarum RM1 enhanced the functional phenolic and flavonoid content, as well as antioxidant and antimicrobial activities. The fermentation with L. plantarum RM1 enhanced the anti-hypertension and anticancer properties of the sea buckthorn juice and gained consumers’ sensorial overall acceptance.

Keywords: sea buckthorn juice, L. plantarum RM1, fermentation, antioxidant, antimicrobial, angiotensin converting enzyme inhibition

Procedia PDF Downloads 50

Authors: Diptimayee Nayak, V. Upadhyay

Abstract:

This paper posits the attempt of conservation and the idea of protected areas from the Marxian primitive accumulation to the politics of sustainability. Using field survey data and secondary literature, this paper analyses an Indian wildlife sanctuary, the Bhitarkanika, Odisha and finds how the hegemony of power among different management regimes attempted for conservation and the present protected area management regime attempted to imbibe the policy of ecotourism for achieving sustainability. The paper contends that the current policy of ecotourism in protected areas acts as a veil for the local deprived people, to avoid many legal conflicts like property rights, livelihood, and man-wildlife issues. Moreover, opening the scope to accumulate on the part of tour operators, the policy of ecotourism establishes a nexus between the profit holders/tour operators (the capitalists) and the power hegemony on the part of management authorities. The sustainability attempt of ecotourism may lead to private benefits maximising the profit accumulation and can expand and continue, showing the bulk of employment generation of local people at petty odd jobs, grabbing a lion share! Positing ecotourism as a capitalist project as against the general assumption of one of the drivers of sustainable development, the paper shows that ecotourism in practice may end up ruining the very social-environmental set up, leading to unsustainability related to waste management, equality, culture, relationship and above all polarised private accumulators in absence of sound mechanism. The paper ends with the caveat that while shopping for neoliberal conservation, the conservators found ecotourism as a product without finalising the hallmark of mechanism/ institutions with appropriate modus operandii to check/guard the quality assurance/standard of ecotourism for sustainability. The paper proposes sound structural and institutional mechanism of ecotourism to be developed to harness sustainability in the local economy as well as in conservation.

Keywords: conservation, ecotourism, Marxian capitalism, protected areas, sustainability

Procedia PDF Downloads 135

Authors: Swati Srivastava, Ashish Kumar Upadhyay

Abstract:

Background: According to United Nation Children’s Fund, it has been estimated that worldwide about 165 million children were stunted in 2012 and India alone accounts for 38% of global burden of stunting. In terms of incidence, India is home of more than 60 million stunted children worldwide. Our study aims to examine the effect of pregnancy intention and maternal postnatal depressive symptoms on early childhood stunting in India. We hypothesized that effect of pregnancy intention and postnatal maternal depressive symptoms were mediated by social support. Methods: We used data from first wave of Young Lives Study India. Out of 2011 children recruited in original cohort, 1833 children had complete information on pregnancy intention, maternal depression and other variables. A series of multivariate logistic regression model were used to examine the effect of pregnancy intention and postnatal depressive symptoms on early childhood stunting. Results: Bivariate result indicates that a higher percent of children born after unintended pregnancy (40%) were stunted than children of intended pregnancy (26%). Likewise, proportion of stunted children was also higher among women of high postnatal depressive symptoms (35%) than low level of depression (24%). Results of multivariate logistic regression model indicate that children born after unintended pregnancy were significantly more likely to be stunted than children born after intended pregnancy (Coefficient: 1.70, CI: 1.17, 2.48). Likewise, early childhood stunting was also associated with maternal postnatal depressive symptoms among women (Coefficient: 1.48, CI: 1.16, 1.88). The effect of pregnancy intention and postnatal depressive symptoms on early childhood stunting remains unchanged after controlling for social support and other variables. Conclusions: The findings of this study provide conclusive evidence regarding consequences of pregnancy intention and postnatal depressive symptoms on early childhood stunting in India. Therefore, there is need to identify the women with unintended pregnancy and incorporate the promotion of mental health into their national reproductive and child health programme.

Keywords: pregnancy intention, postnatal depressive symptoms, social support, childhood stunting, young lives study, India

Procedia PDF Downloads 265

Authors: Rutuja Upadhyay, Anurag Mehra

Abstract:

Solid food foams/cellular foods are colloidal systems which impart structure, texture and mouthfeel to many food products such as bread, cakes, ice-cream, meringues, etc. Their heterogeneous morphology makes the quantification of structure/mechanical relationships complex. The porous structure of solid food foams is highly influenced by the processing conditions, ingredient composition, and their interactions. Sensory perceptions of food foams are dependent on bubble size, shape, orientation, quantity and distribution and determines the texture of foamed foods. The state and structure of the solid matrix control the deformation behavior of the food, such as elasticity/plasticity or fracture, which in turn has an effect on the force-deformation curves. The obvious step in obtaining the relationship between the mechanical properties and the porous structure is to quantify them simultaneously. Here, we attempt to research food foams such as bread dough, baked bread and steamed rice cakes to determine the link between ingredients and the corresponding effect of each of them on the rheology, microstructure, bubble size and texture of the final product. Dynamic rheometry (SAOS), confocal laser scanning microscopy, flatbed scanning, image analysis and texture profile analysis (TPA) has been used to characterize the foods studied. In all the above systems, there was a common observation that when the mean bubble diameter is smaller, the product becomes harder as evidenced by the increase in storage and loss modulus (G′, G″), whereas when the mean bubble diameter is large the product is softer with decrease in moduli values (G′, G″). Also, the bubble size distribution affects texture of foods. It was found that bread doughs with hydrocolloids (xanthan gum, alginate) aid a more uniform bubble size distribution. Bread baking experiments were done to study the rheological changes and mechanisms involved in the structural transition of dough to crumb. Steamed rice cakes with xanthan gum (XG) addition at 0.1% concentration resulted in lower hardness with a narrower pore size distribution and larger mean pore diameter. Thus, control of bubble size could be an important parameter defining final food texture.

Keywords: food foams, rheology, microstructure, texture

Procedia PDF Downloads 307

Authors: I. Upadhyaya, K. Arsi, A. M. Donoghue, C. N. Coon, M. Schlumbohm, M. N. Riaz, M. B. Farnell, A. Upadhyay, A. J. Davis, D. J. Donoghue

Abstract:

Methionine, a sulfur containing amino acid, is essential for healthy poultry production. Synthetic methionine is commonly used as a supplement in conventional poultry. However, for organic poultry, a natural, cost effective source of methionine that can replace synthetic methionine is unavailable. Invasive Asian carp (AC) are a potential natural methionine source; however, there is no proven technology to utilize this fish methionine. Commercially available rendering is environmentally challenging due to the offensive smell produced during production. We explored extrusion technology as a potential cost effective alternative to fish rendering. We also determined the amino acid composition, digestible amino acids and total metabolizable energy (TMEn) for the extruded AC fish meal. Dry extrusion of AC was carried out by mixing the fish with soybean meal (SBM) in a 1:1 proportion to reduce high moisture in the fishmeal using an Insta Pro Jr. dry extruder followed by drying and grinding of the product. To determine the digestible amino acids and TMEn of the extruded product, a colony of cecectomized Bovans White Roosters was used. Adult roosters (48 weeks of age) were fasted for 30 h and tube fed 35 grams of 3 treatments: (1) extruded AC fish meal, (2) SBM and (3) corn. Excreta from each individual bird was collected for the next 48 h. An additional 10 unfed roosters served as endogenous controls. The gross energy and protein content of the feces from the treatments were determined to calculate the TMEn. Fecal samples and treatment feeds were analyzed for amino acid content and percent digestible amino acid. Results from the analysis suggested that addition of Asian carp increased the methionine content of SBM from 0.63 to 0.83%. Also, the digestibility of amino acid and the TMEn values were greater for the AC meal with SBM than SBM alone. The dry extruded AC meal analysis is indicative that the product can replace SBM alone and enhance natural methionine in a standard poultry ration. The results from feed formulation using different concentrations of the AC fish meal depict a potential diet which can supplement the required methionine content in organic poultry production.

Keywords: Asian carp, extrusion, natural methionine, organic poultry

Procedia PDF Downloads 182

Authors: Vaidehi Murarka, Sneha Mehta, Dishant Upadhyay

Abstract:

Our project topic is “Alphabet Recognition using pixel probability distribution”. The project uses techniques of Image Processing and Machine Learning in Computer Vision. Alphabet recognition is the mechanical or electronic translation of scanned images of handwritten, typewritten or printed text into machine-encoded text. It is widely used to convert books and documents into electronic files etc. Alphabet Recognition based OCR application is sometimes used in signature recognition which is used in bank and other high security buildings. One of the popular mobile applications includes reading a visiting card and directly storing it to the contacts. OCR's are known to be used in radar systems for reading speeders license plates and lots of other things. The implementation of our project has been done using Visual Studio and Open CV (Open Source Computer Vision). Our algorithm is based on Neural Networks (machine learning). The project was implemented in three modules: (1) Training: This module aims “Database Generation”. Database was generated using two methods: (a) Run-time generation included database generation at compilation time using inbuilt fonts of OpenCV library. Human intervention is not necessary for generating this database. (b) Contour–detection: ‘jpeg’ template containing different fonts of an alphabet is converted to the weighted matrix using specialized functions (contour detection and blob detection) of OpenCV. The main advantage of this type of database generation is that the algorithm becomes self-learning and the final database requires little memory to be stored (119kb precisely). (2) Preprocessing: Input image is pre-processed using image processing concepts such as adaptive thresholding, binarizing, dilating etc. and is made ready for segmentation. “Segmentation” includes extraction of lines, words, and letters from the processed text image. (3) Testing and prediction: The extracted letters are classified and predicted using the neural networks algorithm. The algorithm recognizes an alphabet based on certain mathematical parameters calculated using the database and weight matrix of the segmented image.

Keywords: contour-detection, neural networks, pre-processing, recognition coefficient, runtime-template generation, segmentation, weight matrix

Procedia PDF Downloads 355

Authors: Ramesh Adsul, Vikas Minchekar

Abstract:

The present study attempts to explore the differences in academic achievement and psychological well being and its components – satisfaction, efficiency, sociability, mental health, interpersonal relations in low and moderate level of hemoglobin of college female students. It also tries to find out how hemoglobin, psychological well –being and academic achievement correlate to each other. For this study 200 (100 low hemoglobin level and 100 moderate hemoglobin level) college female students were selected by random sampling method. This sample is collected from the project ‘Health awareness and hemoglobin improvement programme’, which is being collaboratively conducted by ‘Akshyabhasha, MESA, U.S.A. and Smt. M.G. Kanya Mahavidyalaya, Sangli, Maharashtra, India. Psychological Well-Being Scale was used to collect the data. Students’ academic achievement was collected through college record, and hemoglobin level of female students was collected from project record. Data was analyzed by using independent ‘t’ test and Pearson’s correlation coefficient. The finding of the study revealed significant differences between low hemoglobin and moderate hemoglobin groups regarding efficiency and mental health. No significant difference was observed on satisfaction, sociability and interpersonal relations. It is also found that there is significant difference between low hemoglobin and moderate hemoglobin groups on academic achievement. The study revealed positive correlation between hemoglobin and academic achievement and psychological well-being and academic achievement. Moderate hemoglobin level create more efficiency, better mental health and good academic achievement in female students. One could say that there is significant role hemoglobin plays in psychological well being and academic achievement of college female students. Anemia is widely prevalent in all the states if India among all age groups. In India, college girls contribute major portion of population. It has been reported that 80% female population has hemoglobin deficiency, due to illiteracy of female, family structure, status of women, diet habits, gender discrimination and various superstitions. The deficiency of hemoglobin affects physical and mental health, general behavior and academic performance of students. This study is useful to educational managements, counselors, parents, students and Government also. In the development of personality physical as well as psychological health is essential. This research findings will create awareness about physical and mental health among people and society.

Keywords: academic achievement, college female students, hemoglobin, psychological well-being

Procedia PDF Downloads 266

Authors: Vikas Kumar

Abstract:

Portable batteries are reliable source of mobile energy to power smart wearable electronics, medical devices, communications, and others internet of thing (IoT) devices. There is a continuous increase in demand for thinner, more flexible battery with high energy density and reliability to meet the requirement. For a flexible battery, factors that affect these properties are the stability of current collectors, electrode materials and their interfaces with the corrosive electrolytes. State-of-the-art conventional and flexible batteries utilise carbon as an electrode and current collectors which cause high internal resistance (~100 ohms) and limit the peak current to ~1mA. This makes them unsuitable for a wide range of applications. Replacing the carbon parts with metallic components would reduce the internal resistance (and hence reduce parasitic loss), but significantly increases the risk of corrosion due to galvanic interactions within the battery. To overcome these challenges, low cost electroplated nickel (Ni) on copper (Cu) was studied as a potential anode current collector for a zinc-manganese oxide primary battery with different concentration of NH4Cl/ZnCl2 electrolyte. Using electrical impedance spectroscopy (EIS), we monitored the open circuit potential (OCP) of electroplated nickel (different thicknesses) in different concentration of electrolytes to optimise the thickness of Ni coating. Our results show that electroless Ni coating suffer excessive corrosion in these electrolytes. Corrosion rates of Ni coatings for different concentrations of electrolytes have been calculated with Tafel analysis. These results suggest that for electroplated Ni, channelling and/or open porosity is a major issue, which was confirmed by morphological analysis. These channels are an easy pathway for electrolyte to penetrate thorough Ni to corrode the Ni/Cu interface completely. We further investigated the incorporation of a special printed graphene layer on Ni to provide corrosion protection in this corrosive electrolyte medium. We find that the incorporation of printed graphene layer provides the corrosion protection to the Ni and enhances the chemical bonding between the active materials and current collector and also decreases the overall internal resistance of the battery system.

Keywords: corrosion, electrical impedance spectroscopy, flexible battery, graphene, metal current collector

Procedia PDF Downloads 101

Authors: Vikas Teotia, Sanjay Malhotra, Elina Mishra, Prashant Kumar, R. R. Singh, Priti Ukarde, P. P. Marathe, Y. S. Mayya

Abstract:

Bhabha Atomic Research Centre, Trombay is developing low energy high intensity Proton Accelerator (LEHIPA) as pre-injector for 1 GeV proton accelerator for accelerator driven sub-critical reactor system (ADSS). LEHIPA consists of RFQ (Radio Frequency Quadrupole) and DTL (Drift Tube Linac) as major accelerating structures. DTL is RF resonator operating in TM010 mode and provides longitudinal E-field for acceleration of charged particles. The RF design of drift tubes of DTL was carried out to maximize the shunt impedance; this demands the diameter of drift tubes (DTs) to be as low as possible. The width of the DT is however determined by the particle β and trade-off between a transit time factor and effective accelerating voltage in the DT gap. The array of Drift Tubes inside DTL shields the accelerating particle from decelerating RF phase and provides transverse focusing to the charged particles which otherwise tends to diverge due to Columbic repulsions and due to transverse e-field at entry of DTs. The magnetic lenses housed inside DTS controls the transverse emittance of the beam. Quadrupole magnets are preferred over solenoid magnets due to relative high focusing strength of former over later. The availability of small volume inside DTs for housing magnetic quadrupoles has motivated the usage of permanent magnet quadrupoles rather than Electromagnetic Quadrupoles (EMQ). This provides another advantage as joule heating is avoided which would have added thermal loaded in the continuous cycle accelerator. The beam dynamics requires uniformity of integral magnetic gradient to be better than ±0.5% with the nominal value of 2.05 tesla. The paper describes the magnetic design of the PMQ using Sm2Co17 rare earth permanent magnets. The paper discusses the results of five pre-series prototype fabrications and qualification of their prototype permanent magnet quadrupoles and a full scale DT developed with embedded PMQs. The paper discusses the magnetic pole design for optimizing integral Gdl uniformity and the value of higher order multipoles. A novel but simple method of tuning the integral Gdl is discussed.

Keywords: DTL, focusing, PMQ, proton, rate earth magnets

Procedia PDF Downloads 437

Authors: Hemant Upadhyay, Tarun Kumar Kundu

Abstract:

It is utmost important for a blast furnace operator to understand the mechanisms governing the liquid flow, accumulation, drainage and heat transfer between various phases in blast furnace hearth for a stable and efficient blast furnace operation. Abnormal drainage behavior may lead to high liquid build up in the hearth. Operational problems such as pressurization, low wind intake, and lower material descent rates, normally be encountered if the liquid levels in the hearth exceed a critical limit when Hearth coke and Deadman start to float. Similarly, hot metal temperature is an important parameter to be controlled in the BF operation; it should be kept at an optimal level to obtain desired product quality and a stable BF performance. It is not possible to carry out any direct measurement of above due to the hostile conditions in the hearth with chemically aggressive hot liquids. The objective here is to develop a mathematical model to simulate the variation in hot metal / slag accumulation and temperature during the tapping of the blast furnace based on the computed drainage rate, production rate, mass balance, heat transfer between metal and slag, metal and solids, slag and solids as well as among the various zones of metal and slag itself. For modeling purpose, the BF hearth is considered as a pressurized vessel, filled with solid coke particles. Liquids trickle down in hearth from top and accumulate in voids between the coke particles which are assumed thermally saturated. A set of generic mass balance equations gives the amount of metal and slag intake in hearth. A small drainage (tap hole) is situated at the bottom of the hearth and flow rate of liquids from tap hole is computed taking in account the amount of both the phases accumulated their level in hearth, pressure from gases in the furnace and erosion behaviors of tap hole itself. Heat transfer equations provide the exchange of heat between various layers of liquid metal and slag, and heat loss to cooling system through refractories. Based on all that information a dynamic simulation is carried out which provides real time information of liquids accumulation in hearth before and during tapping, drainage rate and its variation, predicts critical event timings during tapping and expected tapping temperature of metal and slag on preset time intervals. The model is in use at JSPL, India BF-II and its output is regularly cross-checked with actual tapping data, which are in good agreement.

Keywords: blast furnace, hearth, deadman, hotmetal

Procedia PDF Downloads 154

Authors: Vikas S. Minchekar

Abstract:

The eyewitness is a crucial source of evidence in the criminal judicial system. However, rely on the reminiscence of an eyewitness especially intoxicated eyewitness is not always judicious. It might lead to some serious consequences. Day by day, alcohol-related crimes or the criminal incidences in bars, nightclubs, and restaurants are increasing rapidly. Tackling such cases is very complicated to any investigation officers. The people in that incidents are violated due to the alcohol consumption hence, their ability to identify the suspects or recall these phenomena is affected. The studies on the effects of alcohol consumption on motor activities such as driving and surgeries have received much attention. However, the effect of alcohol intoxication on memory has received little attention from the psychology, law, forensic and criminology scholars across the world. In the Indian context, the published articles on this issue are equal to none up to present day. This field experiment investigation aimed at to finding out the effect of alcohol consumption on identification accuracy in lineups. Forty adult, social drinkers, and twenty sober adults were randomly recruited for the study. The sober adults were assigned into 'placebo' beverage group while social drinkers were divided into two group e. g. 'low dose' of alcohol (0.2 g/kg) and 'high dose' of alcohol (0.8 g/kg). The social drinkers were divided in such a way that their level of blood-alcohol concentration (BAC) will become different. After administering the beverages for the placebo group and liquor to the social drinkers for 40 to 50 minutes of the period, the five-minute video clip of mock crime is shown to all in a group of four to five members. After the exposure of video, clip subjects were given 10 portraits and asked them to recognize whether they are involved in mock crime or not. Moreover, they were also asked to describe the incident. The subjects were given two opportunities to recognize the portraits and to describe the events; the first opportunity is given immediately after the video clip and the second was 24 hours later. The obtained data were analyzed by one-way ANOVA and Scheffe’s posthoc multiple comparison tests. The results indicated that the 'high dose' group is remarkably different from the 'placebo' and 'low dose' groups. But, the 'placebo' and 'low dose' groups are equally performed. The subjects in a 'high dose' group recognized only 20% faces correctly while the subjects in a 'placebo' and 'low dose' groups are recognized 90 %. This study implied that the intoxicated witnesses are less accurate to recognize the suspects and also less capable of describing the incidents where crime has taken place. Moreover, this study does not assert that intoxicated eyewitness is generally less trustworthy than their sober counterparts.

Keywords: intoxicated eyewitness, memory, social drinkers, lineups

Procedia PDF Downloads 237

Authors: Rajni Singh, Rakesh Mishra, Mukunda Upadhyay

Abstract:

India is among the nations born out of partition that led to one of the greatest forced migrations that marked the past century. The Indian subcontinent got partitioned into two nation-states, namely India and Pakistan. This led to an unexampled mass displacement of people accounting for about 20 million in the subcontinent as a whole. This exemplifies the socio-political version of displacement, but there are other identified reasons leading to human displacement viz., natural calamities, development projects and people-trafficking and smuggling. Although forced migrations are rare in incidence, they are mostly region-specific and a very less percentage of population appears to be affected by it. However, when this percentage is transcripted in terms of volume, the real impact created by such migration can be realized. Forced migration is thus an issue related to the lives of many people and requires to be addressed with proper intervention. Forced or involuntary migration decimates peoples' assets while taking from them their most basic resources and makes them migrate without planning and intention. This in most cases proves to be a burden on the destination resources. Thus, the question related to their security concerns arise profoundly with regard to the protection and safeguards to these migrants who need help at the place of destination. This brings the human security dimension of forced migration into picture. The present study is an analysis of a sample of 1501 persons by NSSO in India (National Sample Survey Organisation), which identifies three reasons for forced migration- natural disaster, social/political problem and displacement by development projects. It was observed that, of the total forced migrants, about 4/5th comprised of the internally displaced persons. However, there was a huge inflow of such migrants to the country from across the borders also, the major contributing countries being Bangladesh, Pakistan, Sri Lanka, Gulf countries and Nepal. Among the three reasons for involuntary migration, social and political problem is the most prominent in displacing huge masses of population; it is also the reason where the share of international migrants to that of internally displaced is higher compared to the other two factors /reasons. Second to political and social problems, natural calamities displaced a high portion of the involuntary migrants. The present paper examines the factors which increase people's vulnerability to forced migration. On perusing the background characteristics of the migrants it was seen that those who were economically weak and socially fragile are more susceptible to migration. Therefore, getting an insight about this fragile group of society is required so that government policies can benefit these in the most efficient and targeted manner.

Keywords: involuntary migration, displacement, natural disaster, social and political problem

Procedia PDF Downloads 327

Authors: Pramit Garg, Vikas Kumar

Abstract:

In December 2015, all the members of the United Nations Framework Convention on Climate Change (UNFCCC) unanimously adopted the historic Paris Agreement. As per the convention, 197 countries have followed the guidelines of the agreement and have agreed to reduce the use of fossil fuels and also reduce the carbon emission to reach net carbon neutrality by 2050 and reduce the global temperature by 2°C by the year 2100. Globally, transport accounts for 23% of the energy-related CO2 that feeds global warming. Decarbonization of the transport sector is an essential step towards achieving India’s nationally determined contributions and net zero emissions by 2050. Metro rail systems are playing a vital role in the decarbonization of the transport sector as they create metro cities for the “21st-century world” that could ensure “mobility, connectivity, productivity, safety and sustainability” for the populace. Metro rail was introduced in Delhi in 2002 to decarbonize Delhi-National Capital Region and to provide a sustainable mode of public transportation. Metro Rail Projects significantly contribute to pollution reduction and are thus a prerequisite for sustainable development. The Delhi Metro is the 1ˢᵗ metro system in the world to earn carbon credits from Clean Development Mechanism (CDM) projects registered under United Nations Framework Convention on Climate Change. A good Metro Project with reasonable network coverage attracts a modal shift from various private modes and hence fewer vehicles on the road, thus restraining the pollution at the source. The absence of Greenhouse Gas emissions from the vehicle of modal shift passengers and lower emissions due to decongested roads contribute to the reduction in Green House Gas emissions and hence overall reduction in atmospheric pollution. The reduction in emission during the horizon year 2002 to 2019 has been estimated using emission standards and deterioration factor(s) for different categories of vehicles. Presently, our results indicate that the Delhi Metro system has reduced approximately 17.3% of motorized trips by road resulting in an emission reduction significantly. Overall, Delhi Metro, with an immediate catchment area of 17% of the National Capital Territory of Delhi (NCTD), is helping today to reduce 387 tonnes of emissions per day and 141.2 ktonnes of emissions yearly. The findings indicate that the Metro rail system is driving cities towards a more livable environment.

Keywords: Delhi metro, GHG emission, sustainable public transport, urban transport

Procedia PDF Downloads 95

Authors: Rakesh Mishra, Rajni Singh, Mukunda Upadhyay

Abstract:

Since the last few decades, the prima facie of development has shifted towards the working population in India. There has been a paradigm shift in the development approach with the realization that the present demographic dividend has to be harnessed for sustainable development. Rapid urbanization and improved socioeconomic characteristics experienced within its territory has catalyzed various forms of migration into it, resulting in massive transference of workforce between its states. Workforce in any country plays a very crucial role in deciding development of both the places, from where they have out-migrated and the place they are residing currently. In India, people are found to be migrating from relatively less developed states to a well urbanized and developed state for satisfying their neediness. Linking migration to HDI at place of destination, the regression coefficient (β ̂) shows affirmative association between them, because higher the HDI of the place would be, higher would be chance of earning and hence likeliness of the migrants would be more to choose that place as a new destination and vice versa. So the push factor is compromised by the cost of rearing and provides negative impulse on the in migrants letting down their numbers to metro cities or megacities of the states but increasing their mobility to the suburban areas and vice versa. The main objective of the study is to check the role of migration in deciding the dividend of the place of destination as well as people at the place of their usual residence with special focus to highly urban states in India. Idealized scenario of Indian migrants refers to some new theories in making. On analyzing the demographic dividend of the places we got to know that Uttar Pradesh provides maximum dividend to Maharashtra, West Bengal and Delhi, and the demographic divided of migrants are quite comparable to the native’s shares in the demographic dividend in these places. On analyzing the data from National Sample Survey 64th round and Census of India-2001, we have observed that for males in rural areas, the share of unemployed person declined by 9 percentage points (from 45% before migration to 36 % after migration) and for females in rural areas the decline was nearly 12 percentage points (from 79% before migration to 67% after migration. It has been observed that the shares of unemployed males in both rural and urban areas, which were significant before migration, got reduced after migration while the share of unemployed females in the rural as well as in the urban areas remained almost negligible both for before and after migration. So increase in the number of employed after migration provides an indication of changes in the associated cofactors like health and education of the place of destination and arithmetically to the place from where they have migrated out. This paper presents the evidence on the patterns of prevailing migration dynamics and corresponding demographic benefits in India and its states, examines trends and effects, and discusses plausible explanations.

Keywords: migration, demographic shift, human development index, multilevel analysis

Procedia PDF Downloads 361

Authors: Vikas Kumar, Kailash Chandra, Kaomud Tyagi

Abstract:

The insect order Thysanoptera includes small insects commonly called thrips. As insect vectors, only thrips are capable of Tospoviruses transmission (genus Tospovirus, family Bunyaviridae) affecting various crops. Currently, fifteen species of subfamily Thripinae (Thripidae) have been reported as vectors for tospoviruses. Frankliniella schultzei, which is reported as act as a vector for at least five tospovirses, have been suspected to be a species complex with more than one species. It is one of the historical unresolved issues where, two species namely, F. schultzei Trybom and F. sulphurea Schmutz were erected from South Africa and Srilanaka respectively. These two species were considered to be valid until 1968 when sulphurea was treated as colour morph (pale form) and synonymised under schultzei (dark form) However, these two have been considered as valid species by some of the thrips workers. Parallel studies have indicated that brown form of schultzei is a vector for tospoviruses while yellow form is a non-vector. However, recent studies have shown that yellow populations have also been documented as vectors. In view of all these facts, it is highly important to have a clear understanding whether these colour forms represent true species or merely different populations with different vector carrying capacities and whether there is some hidden diversity in 'Frankliniella schultzei species complex'. In this study, we aim to study the 'Frankliniella schultzei species complex' with molecular spectacles with DNA data from India and Australia and Africa. A total of fifty-five specimens was collected from diverse locations in India and Australia. We generated molecular data using partial fragments of mitochondrial cytochrome c oxidase I gene (mtCOI) and 28S rRNA gene. For COI dataset, there were seventy-four sequences, out of which data on fifty-five was generated in the current study and others were retrieved from NCBI. All the four different tree construction methods: neighbor-joining, maximum parsimony, maximum likelihood and Bayesian analysis, yielded the same tree topology and produced five cryptic species with high genetic divergence. For, rDNA, there were forty-five sequences, out of which data on thirty-nine was generated in the current study and others were retrieved from NCBI. The four tree building methods yielded four cryptic species with high bootstrap support value/posterior probability. Here we could not retrieve one cryptic species from South Africa as we could not generate data on rDNA from South Africa and sequence for rDNA from African region were not available in the database. The results of multiple species delimitation methods (barcode index numbers, automatic barcode gap discovery, general mixed Yule-coalescent, and Poisson-tree-processes) also supported the phylogenetic data and produced 5 and 4 Molecular Operational Taxonomic Units (MOTUs) for mtCOI and 28S dataset respectively. These results of our study indicate the likelihood that F. sulphurea may be a valid species, however, more morphological and molecular data is required on specimens from type localities of these two species and comparison with type specimens.

Keywords: DNA barcoding, species complex, thrips, species delimitation

Procedia PDF Downloads 102

Authors: Kaomud Tyagi, Rajasree Chakraborty, Shantanu Kundu, Devkant Singha, Kailash Chandra, Vikas Kumar

Abstract:

The melon thrips, Thrips palmi is a serious pest of a wide range of agriculture crops and also act as vectors for plant viruses (genus Tospovirus, family Bunyaviridae). More molecular data on this species is required to understand the cryptic speciation and evolutionary affiliations. Mitochondrial genomes have been widely used in phylogenetic and evolutionary studies in insect. So far, mitogenomes of five thrips species (Anaphothrips obscurus, Frankliniella intonsa, Frankliniella occidentalis, Scirtothrips dorsalis and Thrips imaginis) is available in the GenBank database. In this study, we sequenced the first complete mitogenome T. palmi and compared it with available thrips mitogenomes. We assembled the mitogenome from the whole genome sequencing data generated using Illumina Hiseq2500. Annotation was performed using MITOS web-server to estimate the location of protein coding genes (PCGs), transfer RNA (tRNAs), ribosomal RNAs (rRNAs) and their secondary structures. The boundaries of PCGs and rRNAs was confirmed manually in NCBI. Phylogenetic analyses were performed using the 13 PCGs data using maximum likelihood (ML) in PAUP, and Bayesian inference (BI) in MrBayes 3.2. The complete mitogenome of T. palmi was 15,333 base pairs (bp), which was greater than the genomes of A. obscurus (14,890bp), F. intonsa (15,215 bp), F. occidentalis (14,889 bp) and S. dorsalis South Asia strain (SA1) (14,283 bp), but smaller than the genomes of T. imaginis (15,407 bp) and S. dorsalis East Asia strain (EA1) (15,343bp). Like in other thrips species, the mitochondrial genome of T. palmi was represented by 37 genes, including 13 PCGs, large and small ribosomal RNA (rrnL and rrnS) genes, 22 transfer RNA (tRNAs) genes (with one extra gene for trn-Serine) and two A+T-rich control regions (CR1 and CR2). Thirty one genes were observed on heavy (H) strand and six genes on the light (L) strand. The six tRNA genes (trnG,trnK, trnY, trnW, trnF, and trnH) were found to be conserved in all thrips species mitogenomes in their locations relative to a protein-coding or rRNA gene upstream or downstream. The gene arrangements of T. palmi is very close to T. imaginis except the rearrangements in tRNAs genes: trnR (arginine), and trnE (glutamic acid) were found to be located between cox3 and CR2 in T. imaginis which were translocated between atp6 and CR1 in T. palmi; trnL1 (Leucine) and trnS1(Serine) were located between atp6 and CR1 in T. imaginis which were translocated between cox3 and CR2 in T. palmi. The location of CR1 upstream of nad5 gene was suggested to be ancestral condition of the thrips species in subfamily Thripinae, was also observed in T. palmi. Both the Maximum likelihood (ML) and Bayesian Inference (BI) phylogenetic trees generated resulted in similar topologies. The T. palmi was clustered with T. imaginis. We concluded that more molecular data on the diverse thrips species from different hierarchical level is needed, to understand the phylogenetic and evolutionary relationships among them.

Keywords: thrips, comparative mitogenomics, gene rearrangements, phylogenetic analysis

Procedia PDF Downloads 137

Authors: Mandeep Singh Azad.Dibyendu Chakraborty, Vikas Vohra

Abstract:

Introduction: Poonch is one of the remotest districts of the Jammu and Kashmir (UT) and situated on international borders. This native poultry population in these areas is quite hardy and thrives well in adverse climatic conditions. Till date, no local breed from this area (Jammu Province) has been characterized thus present study was undertaken with the main objectives of molecular characterization of ChB6 gene in local native chicken of Poonch region located at international borders between India and Pakistan. The chicken B-cell marker (ChB6) gene has been proposed as a candidate gene in regulating B-cell development. Material and Method: RNA was isolated by Blood RNA Purification Kit (HiPura) and Trizol method from whole blood samples. Positive PCR products with size 1110 bp were selected for further purification, sequencing and analysis. The amplified PCR product was sequenced by Sangers dideoxy chain termination method. The obtained sequence of ChB6 gene of Poonchi chicken were compared by MEGAX software. BioEdit software was used to construct phylogenic tree, and Neighbor Joining method was used to infer evolutionary history. In order to compute evolutionary distance Maximum Composite Likelihood method was used. Results: The positively amplified samples of ChB6 genes were then subjected to Sanger sequencing with “Primer Walking. The sequences were then analyzed using MEGA X and BioEdit software. The sequence results were compared with other reported sequence from different breed of chicken and with other species obtained from the NCBI (National Center for Biotechnology Information). ClustalW method using MEGA X software was used for multiple sequence alignment. The sequence results of ChB6 gene of Poonchi chicken was compared with Centrocercus urophasianus, G. gallus mRNA for B6.1 protein, G. gallus mRNA for B6.2, G. gallus mRNA for B6.3, Gallus gallus B6.1, Halichoeres bivittatus, Miniopterus fuliginosus Ferringtonia patagonica, Tympanuchus phasianellus. The genetic distances were 0.2720, 0.0000, 0.0245, 0.0212, 0.0147, 1.6461, 2.2394, 2.0070 and 0.2363 for ChB6 gene of Poonchi chicken sequence with other sequences in the present study respectively. Sequencing results showed variations between different species. It was observed that AT content were higher then GC content for ChB6 gene. The lower AT content suggests less thermostable. It was observed that there was no sequence difference within the Poonchi population for ChB6 gene. The high homology within chicken population indicates the conservation of ChB6 gene. The maximum difference was observed with Miniopterus fuliginosus (Eastern bent-wing bat) followed by Ferringtonia patagonica and Halichoeres bivittatus. Conclusion: Genetic variation is the essential component for genetic improvement. The results of immune related gene Chb6 shows between population genetic variability. Therefore, further association studies of this gene with some prevalent diseases in large population would be helpful to identify disease resistant/ susceptible genotypes in the indigenous chicken population.

Keywords: ChB6, sequencing, ClustalW, genetic distance, poonchi chicken, SNP

Procedia PDF Downloads 34

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

Abstract:

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

Procedia PDF Downloads 481

Authors: Claire Harrison, Raajit K. Rampal, Vikas Gupta, Srdan Verstovsek, Moshe Talpaz, Jean-Jacques Kiladjian, Ruben Mesa, Andrew Kuykendall, Alessandro Vannucchi, Francesca Palandri, Sebastian Grosicki, Timothy Devos, Eric Jourdan, Marielle J. Wondergem, Haifa Kathrin Al-Ali, Veronika Buxhofer-Ausch, Alberto Alvarez-Larrán, Sanjay Akhani, Rafael Muñoz-Carerras, Yury Sheykin, Gozde Colak, Morgan Harris, John Mascarenhas

Abstract:

Myelofibrosis (MF) is characterized by bone marrow fibrosis, anemia, splenomegaly and constitutional symptoms. Progressive bone marrow fibrosis results from aberrant megakaryopoeisis and expression of proinflammatory cytokines, both of which are heavily influenced by bromodomain and extraterminal domain (BET)-mediated gene regulation and lead to myeloproliferation and cytopenias. Pelabresib (CPI-0610) is an oral small-molecule investigational inhibitor of BET protein bromodomains currently being developed for the treatment of patients with MF. It is designed to downregulate BET target genes and modify nuclear factor kappa B (NF-κB) signaling. MANIFEST-2 was initiated based on data from Arm 3 of the ongoing Phase 2 MANIFEST study (NCT02158858), which is evaluating the combination of pelabresib and ruxolitinib in Janus kinase inhibitor (JAKi) treatment-naïve patients with MF. Primary endpoint analyses showed splenic and symptom responses in 68% and 56% of 84 enrolled patients, respectively. MANIFEST-2 (NCT04603495) is a global, Phase 3, randomized, double-blind, active-control study of pelabresib and ruxolitinib versus placebo and ruxolitinib in JAKi treatment-naïve patients with primary MF, post-polycythemia vera MF or post-essential thrombocythemia MF. The aim of this study is to evaluate the efficacy and safety of pelabresib in combination with ruxolitinib. Here we report updates from a recent protocol amendment. The MANIFEST-2 study schema is shown in Figure 1. Key eligibility criteria include a Dynamic International Prognostic Scoring System (DIPSS) score of Intermediate-1 or higher, platelet count ≥100 × 10^9/L, spleen volume ≥450 cc by computerized tomography or magnetic resonance imaging, ≥2 symptoms with an average score ≥3 or a Total Symptom Score (TSS) of ≥10 using the Myelofibrosis Symptom Assessment Form v4.0, peripheral blast count <5% and Eastern Cooperative Oncology Group performance status ≤2. Patient randomization will be stratified by DIPSS risk category (Intermediate-1 vs Intermediate-2 vs High), platelet count (>200 × 10^9/L vs 100–200 × 10^9/L) and spleen volume (≥1800 cm^3 vs <1800 cm^3). Double-blind treatment (pelabresib or matching placebo) will be administered once daily for 14 consecutive days, followed by a 7 day break, which is considered one cycle of treatment. Ruxolitinib will be administered twice daily for all 21 days of the cycle. The primary endpoint is SVR35 response (≥35% reduction in spleen volume from baseline) at Week 24, and the key secondary endpoint is TSS50 response (≥50% reduction in TSS from baseline) at Week 24. Other secondary endpoints include safety, pharmacokinetics, changes in bone marrow fibrosis, duration of SVR35 response, duration of TSS50 response, progression-free survival, overall survival, conversion from transfusion dependence to independence and rate of red blood cell transfusion for the first 24 weeks. Study recruitment is ongoing; 400 patients (200 per arm) from North America, Europe, Asia and Australia will be enrolled. The study opened for enrollment in November 2020. MANIFEST-2 was initiated based on data from the ongoing Phase 2 MANIFEST study with the aim of assessing the efficacy and safety of pelabresib and ruxolitinib in JAKi treatment-naïve patients with MF. MANIFEST-2 is currently open for enrollment.

Keywords: CPI-0610, JAKi treatment-naïve, MANIFEST-2, myelofibrosis, pelabresib

Procedia PDF Downloads 147