Search results for: Vikas Dangi
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 55

Search results for: Vikas Dangi

25 Development and Characterization of Site Specific Peptide Conjugated Polymeric Nanoparticles for Efficient Delivery of Paclitaxel

Authors: Madhu Gupta, Vikas Sharma, Suresh P. Vyas

Abstract:

CD13 receptors are abundantly overexpressed in tumor cells as well as in neovasculature. The CD13 receptors were selected as a targeted site and polymeric nanoparticles (NPs) as a targeted delivery system. By combining these, a cyclic NGR (cNGR) peptide ligand was coupled on the terminal end of polyethylene glycol-b-poly(lactic-co-glycolic acid) (PEG-b-PLGA) and prepared the dual targeted-NPs (cNGR-PEG-PTX-NPs) to enhance the intracellular delivery of anticancer drug to tumor cells and tumor endothelial cells via ligand-receptor interaction. In-vitro cytotoxicity studies confirmed that the presence of cNGR enhanced the cytotoxic efficiency by 2.8 folds in Human Umbilical Vein Endothelial (HUVEC) cells, while cytotoxicity was improved by 2.6 folds in human fibrosarcoma (HT-1080) cells as compared to non-specific stealth NPs. Compared with other tested NPs, cNGR-PEG-PTX-NPs revealed more cytotoxicity by inducing more apoptosis and higher intracellular uptake. The tumor volume inhibition rate was 59.7% in case of cNGR-PEG-PTX-NPs that was comparatively more with other formulations, indicating that cNGR-PEG-PTX-NPs could more effectively inhibit tumor growth. As a consequence, the cNGR-PEG-PTX-NPs play a key role in enhancing tumor therapeutic efficiency for treatment of CD13 receptor specific solid tumor.

Keywords: cyclic NGR, CD13 receptor, targeted polymeric NPs, solid tumor, intracellular delivery

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24 Analysis of Stall Angle Delay in Airfoil Coupled with Spinning Cylinder

Authors: N. Kiran, S. A. Vikas, Yatish Chandra, S. Srinivasan

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Several Centuries ago, the aerodynamic studies on rotating cylinders and spheres have started. From the observation, the rotation of a cylinder has a remarkable effect on the aerodynamic characteristics is noticed. In case of airfoils as the angle of attack increases, the drag increases with reduction in lift i.e at the critical angle of attack. If at this point a strong impulse is imparted to the boundary layer by means of a spinning cylinder, the re-energisation of boundary layer is achieved and hence delaying the boundary layer separation and stalling characteristics. Analysis of aerodynamic effects spinning cylinder either at leading edge or at trailing edge of the airfoil is carried in the past, the positioning of cylinder close to trailing edge and its effects in delaying the stall are yet to be analyzed in depth. This paper aim is to understand the combined aerodynamic effects of coupling the spinning cylinder with the airfoil closer to the Trailing edge, by considering different spin ratio of the cylinder, its location and geometrical parameters in relation to the chord of the airfoil. From the analysis, it was observed that the spinning cylinder speed of rotation and location had a impact on stalling characteristics for a prescribed free stream condition. The results predicted through CFD analysis and experimental analysis showed a raise in aerodynamic efficiency and as the spin ratio increases, increase in stalling angle of attack is noticed when compared to the airfoil without spinning cylinder.

Keywords: aerodynamics, airfoil, spinning cylinder, stalling

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23 Modeling Slow Crack Growth under Thermal and Chemical Effects for Fitness Predictions of High-Density Polyethylene Material

Authors: Luis Marquez, Ge Zhu, Vikas Srivastava

Abstract:

High-density polyethylene (HDPE) is one of the most commonly used thermoplastic polymer materials for water and gas pipelines. Slow crack growth failure is a well-known phenomenon in high-density polyethylene material and causes brittle failure well below the yield point with no obvious sign. The failure of transportation pipelines can cause catastrophic environmental and economic consequences. Using the non-destructive testing method to predict slow crack growth failure behavior is the primary preventative measurement employed by the pipeline industry but is often costly and time-consuming. Phenomenological slow crack growth models are useful to predict the slow crack growth behavior in the polymer material due to their ability to evaluate slow crack growth under different temperature and loading conditions. We developed a quantitative method to assess the slow crack growth behavior in the high-density polyethylene pipeline material under different thermal conditions based on existing physics-based phenomenological models. We are also working on developing an experimental protocol and quantitative model that can address slow crack growth behavior under different chemical exposure conditions to improve the safety, reliability, and resilience of HDPE-based pipeline infrastructure.

Keywords: mechanics of materials, physics-based modeling, civil engineering, fracture mechanics

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22 The Impact of Smartphone Applications on Consumer Attitude towards Brands

Authors: Nikita Bharadia, Vikas Gupta, Sushant Koshy

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Mobile phone applications (“apps”) have generated substantial interest among marketers and researchers because of the developments in the smartphone technology and the availability of affordable phones to a large number of consumers. Apps are enabling brands to engage with consumers at any time and any place. This study utilizes a pre-test/post-test experimental design to determine if apps can have a persuasive impact on the consumer attitude towards the brand and her purchase intention. The study also tests the impact of informational vs. interactive style of apps on categories with high and low level of involvement. The results show that for high involvement brands, consumers have a predetermined brand image and apps that satisfy consumer needs through an interactive interface can increase purchase intention. For low involvement brands, while informational apps do not create substantial engagement, interactive apps can increase consumer focus on the brand and establish personal connect with the consumers. This has a positive impact in the attitude towards the brand. These results suggest that understanding how to maximize the consumer interaction with mobile phone apps will be a key topic of future research. This research indicates that managers need to evaluate the how apps can solve consumer needs before investing resources towards digital marketing campaign for their brands, following the global trend to capitalize on the digital platforms.

Keywords: App execution style, high and low involvement categories, mobile marketing, smartphone applications

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21 Comparative Study of Non-Identical Firearms with Priority to Repair Subject to Inspection

Authors: A. S. Grewal, R. S. Sangwan, Dharambir, Vikas Dhanda

Abstract:

The purpose of this paper is to develop and analyze two reliability models for a system of non-identical firearms – one is standard firearm (called as original unit) and the other is a country-made firearm (called as duplicate /substandard unit). There is a single server who comes immediately to do inspection and repair whenever needed. On the failure of standard firearm, the server inspects the operative country-made firearm to see whether the unit is capable of performing the desired function well or not. If country-made firearm is not capable to do so, the operation of the system is stopped and server starts repair of the standard firearms immediately. However, no inspection is done at the failure of the country-made firearm as the country-made firearm alone is capable of performing the given task well. In model I, priority to repair the standard firearm is given in case system fails completely and country-made firearm is already under repair, whereas in model II there is no such priority. The failure and repair times of each unit are assumed to be independent and uncorrelated random variables. The distributions of failure time of the units are taken as negative exponential while that of repair and inspection times are general. By using semi-Markov process and regenerative point technique some econo-reliability measures are obtained. Graphs are plotted to compare the MTSF (mean time to system failure), availability and profit of the models for a particular case.

Keywords: non-identical firearms, inspection, priority to repair, semi-Markov process, regenerative point

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20 Surface Nanostructure Developed by Ultrasonic Shot Peening and Its Effect on Low Cycle Fatigue Life of the IN718 Superalloy

Authors: Sanjeev Kumar, Vikas Kumar

Abstract:

Inconel 718 (IN718) is a high strength nickel-based superalloy designed for high-temperature applications up to 650 °C. It is widely used in gas turbines of jet engines and related aerospace applications because of its good mechanical properties and structural stability at elevated temperatures. Because of good performance ratio and excellent process capability, this alloy has been used predominantly for aeronautic engine components like compressor disc and compressor blade. The main precipitates that contribute to high-temperature strength of IN718 are γʹ Ni₃(Al, Ti) and mainly γʹʹ (Ni₃ Nb). Various processes have been used for modification of the surface of components, such as Laser Shock Peening (LSP), Conventional Shot Peening (SP) and Ultrasonic Shot Peening (USP) to induce compressive residual stress (CRS) and development of fine-grained structure in the surface region. Surface nanostructure by ultrasonic shot peening is a novel methodology of surface modification to improve the overall performance of structural components. Surface nanostructure was developed on the peak aged IN718 superalloy using USP and its effect was studied on low cycle fatigue (LCF) life. Nanostructure of ~ 49 to 73 nm was developed in the surface region of the alloy by USP. The gage section of LCF samples was USPed for 5 minutes at a constant frequency of 20 kHz using StressVoyager to modify the surface. Strain controlled cyclic tests were performed for non-USPed and USPed samples at ±Δεt/2 from ±0.50% to ±1.0% at strain rate (ė) 1×10⁻³ s⁻¹ under reversal loading (R=‒1) at room temperature. The fatigue life of the USPed specimens was found to be more than that of the non-USPed ones. LCF life of the USPed specimen at Δεt/2=±0.50% was enhanced by more than twice of the non-USPed specimen.

Keywords: IN718 superalloy, nanostructure, USP, LCF life

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19 Enhancing National Integrity through Teaching Secular Perspectives in Medieval Indian History Curricula: A Secular Paradigms

Authors: Deepak Deshpande, Vikas Minchekar

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Day by day in modern India communal forces became stronger and stronger. Each and every caste group trying to show their strength through massive marches. Such kind of marches or ralliesruinous national integrity in India. To test this assumption present investigation has been carried out. This research was undertaken by using survey techniques. The study has been carried out in two phases. In the first stage, the students’ attitudes were collected while in the second phase the views of the members of the historical association were collected. The social dominance orientation scale and sources of social dominance inventory have been administered on 200 college students belonging to Maratha caste. Analyzed data revealed ahigh level of social dominance in Maratha caste students. Approximately, 80 percent students have reported that they have learned such dominance from the medieval history. The other sources disappear very less prominent. These results and present Indian social situation have been communicated with the members of the historical association of India. The majority members of this association agreed with this reality. The consensus also received on that Maratha caste person experiencing dominance due to the misinterpretation of the King Shivaji Empire; synchronize by politicians. The survey monkey app was used through electronic mail to collect the views on ‘The attitude towards the modification of curricula questionnaire’. The maximum number of members of the historical association agreed to employ to teach the medieval Indian history accordingly the secular perspectives.

Keywords: social dominance orientation, secular perceptive, national integrity, Maratha caste and medieval Indian history

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18 Osteoprotective Effect of Lawsonia inermis

Authors: Suraj Muke, Vikas Mankumare, Sadhana Sathaye

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Osteoporosis is the most common metabolic bone disease which affects an estimated 25 million people worldwide, leading to 1 million fractures, 40,000 annual deaths and health costs of billions of dollars. It is estimated that about 80% of total osteoporosis patients are women, amongst which majority are above the age of 45 years. Postmenopausal osteoporosis is associated with lack of intestinal calcium absorption, increasing pro-oxidant and inflammatory mediators. Lawsonia inermis is a biennial dicotyledonous herbaceous shrub is reported to possess a high flavonoid, high phenolic and Inhibitors of osteoclastogenesis like Daphneside and Daphnorin. The present study aimed to screen osteoprotective effect of methanolic extract of Lawsonia inermis (LIM) in rat model along with its antioxidant activity. LIM shows phenolic content 146.3Milligrams of Gallic acid equivalent present per gram of extract and 19.8 Milligrams of rutin per gram of extract of Total flavonoid content with IC50 value 42.99μg/ml. bilateral ovariectomized rat model in which Healthy female wistar rats were used for screening. Treatment with LIM was carried out using graded doses of 25mg/kg, 50mg/kg and 100mg/kg for period of 28 days. The negative control group comprised of ovariectomized rats along with saline treatment for four weeks whereas sham operated rats were used as positive control.LIM showed a decrease in bone turnover by preventing loss of urinary calcium and phosphorous moreover it decreased the alkaline phosphatase levels and loss of bone density is prevented by LIM suggesting decrease in osteoclast activity.

Keywords: antioxidant, osteoclast, osteoporosis, ovariectomized

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17 Temporal Transformation of Built-up Area and its Impact on Urban Flooding in Hyderabad, India

Authors: Subbarao Pichuka, Amar Balakrishna Tej, Vikas Vemula

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In recent years, the frequency and intensity of urban floods have increased due to climate change all over the world provoking a significant loss in terms of human lives and property. This study investigates the effect of Land Use and Land Cover (LULC) changes and population growth on the urban environmental conditions in the Indian metropolitan city namely Hyderabad. The centennial built-up area data have been downloaded from the Global Human Settlement Layer (GHSL) web portal for various periods (1975 to 2014). The ArcGIS version 10.8 software is employed to convert the GHSL data into shape files and also to calculate the amount of built-up area in the study locations. The decadal population data are obtained from the Census from 1971 to 2011 and forecasted for the required years (1975 and 2014) utilizing the Geometric Increase Method. Next, the analysis has been carried out with respect to the increase in population and the corresponding rise in the built-up area. Further the effects of extreme rainfall events, which exacerbate urban flooding have also been reviewed. Results demonstrate that the population growth was the primary cause of the increase in impervious surfaces in the urban regions. It in turn leads to the intensification of surface runoff and thereby leads to Urban flooding. The built-up area has been doubled from 1975 to 2014 and the population growth has been observed between 109.24% to 400% for the past four decades (1971 to 2014) in the study area (Hyderabad). Overall, this study provides the hindsight on the current urban flooding scenarios, and the findings of this study can be used in the future planning of cities.

Keywords: urban LULC change, urban flooding, GHSL built-up data, climate change, ArcGIS

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16 Double Liposomes Based Dual Drug Delivery System for Effective Eradication of Helicobacter pylori

Authors: Yuvraj Singh Dangi, Brajesh Kumar Tiwari, Ashok Kumar Jain, Kamta Prasad Namdeo

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The potential use of liposomes as drug carriers by i.v. injection is limited by their low stability in blood stream. Firstly, phospholipid exchange and transfer to lipoproteins, mainly HDL destabilizes and disintegrates liposomes with subsequent loss of content. To avoid the pain associated with injection and to obtain better patient compliance studies concerning various dosage forms, have been developed. Conventional liposomes (unilamellar and multilamellar) have certain drawbacks like low entrapment efficiency, stability and release of drug after single breach in external membrane, have led to the new type of liposomal systems. The challenge has been successfully met in the form of Double Liposomes (DL). DL is a recently developed type of liposome, consisting of smaller liposomes enveloped in lipid bilayers. The outer lipid layer of DL can protect inner liposomes against various enzymes, therefore DL was thought to be more effective than ordinary liposomes. This concept was also supported by in vitro release characteristics i.e. DL formation inhibited the release of drugs encapsulated in inner liposomes. DL consists of several small liposomes encapsulated in large liposomes, i.e., multivesicular vesicles (MVV), therefore, DL should be discriminated from ordinary classification of multilamellar vesicles (MLV), large unilamellar vesicles (LUV), small unilamellar vesicles (SUV). However, for these liposomes, the volume of inner phase is small and loading volume of water-soluble drugs is low. In the present study, the potential of phosphatidylethanolamine (PE) lipid anchored double liposomes (DL) to incorporate two drugs in a single system is exploited as a tool to augment the H. pylori eradication rate. Preparation of DL involves two steps, first formation of primary (inner) liposomes by thin film hydration method containing one drug, then addition of suspension of inner liposomes on thin film of lipid containing the other drug. The success of formation of DL was characterized by optical and transmission electron microscopy. Quantitation of DL-bacterial interaction was evaluated in terms of percent growth inhibition (%GI) on reference strain of H. pylori ATCC 26695. To confirm specific binding efficacy of DL to H. pylori PE surface receptor we performed an agglutination assay. Agglutination in DL treated H. pylori suspension suggested selectivity of DL towards the PE surface receptor of H. pylori. Monotherapy is generally not recommended for treatment of a H. pylori infection due to the danger of development of resistance and unacceptably low eradication rates. Therefore, combination therapy with amoxicillin trihydrate (AMOX) as anti-H. pylori agent and ranitidine bismuth citrate (RBC) as antisecretory agent were selected for the study with an expectation that this dual-drug delivery approach will exert acceptable anti-H. pylori activity.

Keywords: Helicobacter pylorI, amoxicillin trihydrate, Ranitidine Bismuth citrate, phosphatidylethanolamine, multi vesicular systems

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15 Classification System for Soft Tissue Injuries of Face: Bringing Objectiveness to Injury Severity

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

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14 Effect of Supplementation of Rough Lemon Juice, Amla Juice and Aloe Vera Gel on Physio-biochemical and Hematological Parameters of Broiler Chicken During Summer Season

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

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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

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13 Studies on the Characterization and Machinability of Duplex Stainless Steel 2205 during Dry Turning

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

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12 Using Hyperspectral Sensor and Machine Learning to Predict Water Potentials of Wild Blueberries during Drought Treatment

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

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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

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11 The Role of Hemoglobin in Psychological Well Being and Academic Achievement of College Female Students

Authors: Ramesh Adsul, Vikas Minchekar

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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

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10 Flexible Current Collectors for Printed Primary Batteries

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

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9 Design and Development of Permanent Magnet Quadrupoles for Low Energy High Intensity Proton Accelerator

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

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8 [Keynote Talk]: The Intoxicated Eyewitness: Effect of Alcohol Consumption on Identification Accuracy in Lineup

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

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7 Delhi Metro: A Race towards Zero Emission

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

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6 One Species into Five: Nucleo-Mito Barcoding Reveals Cryptic Species in 'Frankliniella Schultzei Complex': Vector for Tospoviruses

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

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5 Forest Fire Burnt Area Assessment in a Part of West Himalayan Region Using Differenced Normalized Burnt Ratio and Neural Network Approach

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

Abstract:

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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4 The First Complete Mitochondrial Genome of Melon Thrips, Thrips palmi (Thripinae: Thysanoptera): Vector for Tospoviruses

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

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3 Molecular Characterization of Chicken B Cell Marker (ChB6) in Native Chicken of Poonch Region from International Borders of India and Pakistan

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

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2 Amifostine Analogue, Drde-30, Attenuates Radiation-Induced Lung Injury in Mice

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

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1 MANIFEST-2, a Global, Phase 3, Randomized, Double-Blind, Active-Control Study of Pelabresib (CPI-0610) and Ruxolitinib vs. Placebo and Ruxolitinib in JAK Inhibitor-Naïve Myelofibrosis Patients

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

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