Search results for: Mahesh N. Varma
Commenced in January 2007
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Edition: International
Paper Count: 73

Search results for: Mahesh N. Varma

43 Three-Dimensional, Non-Linear Finite Element Analysis of Bullet Penetration through Thin AISI 4340 Steel Target Plate

Authors: Abhishek Soni, A. Kumaraswamy, M. S. Mahesh

Abstract:

Bullet penetration in steel plate is investigated with the help of three-dimensional, non-linear, transient, dynamic, finite elements analysis using explicit time integration code LSDYNA. The effect of large strain, strain-rate and temperature at very high velocity regime was studied from number of simulations of semi-spherical nose shape bullet penetration through single layered circular plate with 2 mm thickness at impact velocities of 500, 1000, and 1500 m/s with the help of Johnson Cook material model. Mie-Gruneisen equation of state is used in conjunction with Johnson Cook material model to determine pressure-volume relationship at various points of interests. Two material models viz. Plastic-Kinematic and Johnson- Cook resulted in different deformation patterns in steel plate. It is observed from the simulation results that the velocity drop and loss of kinetic energy occurred very quickly up to perforation of plate, after that the change in velocity and changes in kinetic energy are negligibly small. The physics behind this kind of behaviour is presented in the paper.

Keywords: AISI 4340 steel, ballistic impact simulation, bullet penetration, non-linear FEM

Procedia PDF Downloads 177
42 Numerical Investigation of Static and Dynamic Responses of Fiber Reinforced Sand

Authors: Sandeep Kumar, Mahesh Kumar Jat, Rajib Sarkar

Abstract:

Soil reinforced with randomly distributed fibers is an attractive means to improve the performance of soil in a cost effective manner. Static and dynamic characterization of fiber reinforced soil have become important to evaluate adequate performance for all classes of geotechnical engineering problems. Present study investigates the behaviour of fiber reinforced cohesionless soil through numerical simulation of triaxial specimen. The numerical model has been validated with the existing literature of laboratory triaxial compression testing. A parametric study has been done to find out optimum fiber content for shear resistance. Cyclic triaxial testing has been simulated and the stress-strain response of fiber-reinforced sand has been examined considering different combination of fiber contents. Shear modulus values and damping values of fiber-reinforced sand are evaluated. It has been observed from results that for 1.0 percent fiber content shear modulus increased 2.28 times and damping ratio decreased 4.6 times. The influence of amplitude of cyclic strain, confining pressure and frequency of loading on the dynamic properties of fiber reinforced sand has been investigated and presented.

Keywords: damping, fiber reinforced soil, numerical modelling, shear modulus

Procedia PDF Downloads 249
41 Sitagliptin-AntiCD4 Mab Conjugated T Cell Targeting Therapy for the Effective Treatment of Type I Diabetes

Authors: T. Mahesh, M. K. Samanta

Abstract:

Antibody dug conjugate (ADC’s) concept is a less explored and more trustable for the treatment of Type 1 diabetes (T1D). T1D is thought to arise from selective immunologically mediated destruction of the insulin- producing β-cells in the pancreatic islets of Langerhans with consequent insulin deficiency. It is evident that type 1 diabetes can be conquered, by 1) to stop immune destruction of βcells, 2) to replace or regenerate β-cells, and 3) to preserve β-cell function and mass. Many studies found that the regulatory T cells (Tregs) are crucial for the maintenance of immunological tolerance. Immune tolerance is liable for the activation of the Th1 response. The important role of Th1 response in pathology of T1D entails the depletion of CD4+ T cells, which initiated the use of anti-CD4 monoclonal antibodies (mAbs) against CD4+ T cells to interfere with induction of T1D.Insulin is regulated by Glucagon-Like Peptide-1 hormone (GLP-1) which also stimulates β-cells proliferation as the half-life of GLP-1 harmone is less due to rapid degradation by DPP-IV enzyme an alternative DPP-IV-inhibitors can increase the half-life of GLP-1 through which it conquers the replacement and reserve β-cells mass. Thus in the present study Anti-CD4 mAb was conjugated with Sitagliptin which is a DPP-IV inhibitor Drug loaded in Nanoparticles through Sulfo-MBS cross-linkers. The above study can be an effective approach for treatment to overcome the Passive subcutaneous insulin therapy.

Keywords: antibody drug conjugates, anti-CD4 Mab, DPP IV inhibitors, GLP-1

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40 Serial Position Curves under Compressively Expanding and Contracting Schedules of Presentation

Authors: Priya Varma, Denis John McKeown

Abstract:

Psychological time, unlike physical time, is believed to be ‘compressive’ in the sense that the mental representations of a series of events may be internally arranged with ever decreasing inter-event spacing (looking back from the most recently encoded event). If this is true, the record within immediate memory of recent events is severely temporally distorted. Although this notion of temporal distortion of the memory record is captured within some theoretical accounts of human forgetting, notably temporal distinctiveness accounts, the way in which the fundamental nature of the distortion underpins memory and forgetting broadly is barely recognised or at least directly investigated. Our intention here was to manipulate the spacing of items for recall in order to ‘reverse’ this supposed natural compression within the encoding of the items. In Experiment 1 three schedules of presentation (expanding, contracting and fixed irregular temporal spacing) were created using logarithmic spacing of the words for both free and serial recall conditions. The results of recall of lists of 7 words showed statistically significant benefits of temporal isolation, and more excitingly the contracting word series (which we may think of as reversing the natural compression within the mental representation of the word list) showed best performance. Experiment 2 tested for effects of active verbal rehearsal in the recall task; this reduced but did not remove the benefits of our temporal scheduling manipulation. Finally, a third experiment used the same design but with Chinese characters as memoranda, in a further attempt to subvert possible verbal maintenance of items. One change to the design here was to introduce a probe item following the sequence of items and record response times to this probe. Together the outcomes of the experiments broadly support the notion of temporal compression within immediate memory.

Keywords: memory, serial position curves, temporal isolation, temporal schedules

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39 Gene Expression Profile Reveals Breast Cancer Proliferation and Metastasis

Authors: Nandhana Vivek, Bhaskar Gogoi, Ayyavu Mahesh

Abstract:

Breast cancer metastasis plays a key role in cancer progression and fatality. The present study examines the potential causes of metastasis in breast cancer by investigating the novel interactions between genes and their pathways. The gene expression profile of GSE99394, GSE1246464, and GSE103865 was downloaded from the GEO data repository to analyze the differentially expressed genes (DEGs). Protein-protein interactions, target factor interactions, pathways and gene relationships, and functional enrichment networks were investigated. The proliferation pathway was shown to be highly expressed in breast cancer progression and metastasis in all three datasets. Gene Ontology analysis revealed 11 DEGs as gene targets to control breast cancer metastasis: LYN, DLGAP5, CXCR4, CDC6, NANOG, IFI30, TXP2, AGTR1, MKI67, and FTH1. Upon studying the function, genomic and proteomic data, and pathway involvement of the target genes, DLGAP5 proved to be a promising candidate due to it being highly differentially expressed in all datasets. The study takes a unique perspective on the avenues through which DLGAP5 promotes metastasis. The current investigation helps pave the way in understanding the role DLGAP5 plays in metastasis, which leads to an increased incidence of death among breast cancer patients.

Keywords: genomics, metastasis, microarray, cancer

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38 Isolation and Identification of Cytotoxic Compounds from Fruticose Lichen Roccella montagnei, and It’s in Silico Docking Study against CDK-10

Authors: Tripti Mishra, Shipra Shukla, Sanjeev Meena, , Ruchi Singh, Mahesh Pal, D. K. Upreti, Dipak Datta

Abstract:

Roccella montagnei belongs to lichen family Roccelleceae growing luxuriantly along the coastal regions of India. As Roccella has been shown to be bioactive, we prepared methanolic extract and assessed its anticancer potential. The methanolic extract showed significant in vitro cytotoxic activity against four human cancer cell lines such as Colon (DLD-1, SW-620), Breast (MCF-7), Head and Neck (FaDu). This prompted us to isolate bioactive compounds through column chromatography. Two compounds Roccellic acid and Everninic acid have been isolated, out of which Everninic acid is reported for the first time. Both the compounds have been tested for in vitro cytotoxic activity in which Roccellic acid showed strong anticancer activity as compared to the Everninic acid. CDK-10 (Cyclin-dependent kinase) contributes to proliferation of cancer cells, and aberrant activity of these kinases has been reported in a wide variety of human cancers. These kinases, therefore, constitute biomarkers of proliferation and attractive pharmacological targets for the development of anticancer therapeutics. Therefore both the isolated compounds were tested for in silico molecular docking study against CDK-10 isomer enzyme to support the cytotoxic activity.

Keywords: cytotoxic activity, everninic acid, roccellic acid, R. montagnei

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37 In-Silico Evaluation and Antihyperglycemic Potential of Leucas Cephalotes

Authors: Anjali Verma, Mahesh Pal, Veena Pande, Dalip Kumar Upreti

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The present study is carried out to explore the anti-hyperglycemic activity of Leucas cephalotes plant parts. A fruit, leaves, stems, and roots part of the Leucas cephalotes has been extracted in ethanol and have been evaluated for anti-hyperglycemic activity. The present study indicated that, ethanolic extract of fruit and leaves have shown significant α- amylase inhibitory activity with IC50 value of 92.86 ± 0.89 μg/mL and 98.09 ± 0.69 μg/mL respectively. Two known compounds β-sitosterol and lupeol were isolated from ethanolic extract of L. cephalotes leaves and were subjected to anti-hyperglycemic activity. Lupeol shows the best activity with IC50 55.73 ± 0.47 μg/mL and the results were verified by docking study of these compounds with mammalian α-amylase was carried out on its active site. It was concluded from the study that β-sitosterol and lupeol form one H-bond interactions with the active site residues either Asp212 or Thr21. The estimated free energy binding of β-sitosterol was found to be -9.47 kcal mol-1 with an estimated inhibition constant (Ki) of 558.94 nmol whereas the estimated free energy binding of lupeol was -11.73 kcal mol-1 with an estimated inhibition constant (Ki) of 476.71pmmol. The present study clearly showed that lupeol is more potent in comparison to β-sitosterol. The study indicates that L. cephalotes have significant potential to inhibit α-amylase enzyme.

Keywords: alpha-amylase, beta-sitosterol, hyperglycemia, lupeol

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36 Instrumentation for Engine Start Cycle Characterization at Cold Weather High Altitude Condition

Authors: Amit Kumar Gupta, Rohit Vashistha, G. P. Ravishankar, Mahesh P. Padwale

Abstract:

A cold soaked gas turbine engine have known starting problems in high altitude and low temperature conditions. The high altitude results in lower ambient temperature, pressure, and density. Soaking at low temperature leads to higher oil viscosity, increasing the engine starter system torque requirement. Also, low temperature soaks results in a cold compressor rotor and casing. Since the thermal mass of rotor is higher than casing, casing expands faster, thereby, increasing the blade-casing tip clearance. The low pressure flow over the compressor blade coupled with the secondary flow through the compressor tip clearance during start result in stall inception. The present study discusses engine instrumentation required for capturing the stall inception event. The engine fan exit and combustion chamber were instrumented with dynamic pressure probes to capture the pressure characteristic and clamp-on current meter on primary igniter cable to capture ignition event during start cycle. The experiment was carried out at 10500 Ft. pressure altitude and -15°C ambient temperature. The high pressure compressor stall events were recorded during the starts.

Keywords: compressor inlet, dynamic pressure probe, engine start cycle, flight test instrumentation

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35 Sulfate Reducing Bacteria Based Bio-Electrochemical System: Towards Sustainable Landfill Leachate and Solid Waste Treatment

Authors: K. Sushma Varma, Rajesh Singh

Abstract:

Non-engineered landfills cause serious environmental damage due to toxic emissions and mobilization of persistent pollutants, organic and inorganic contaminants, as well as soluble metal ions. The available treatment technologies for landfill leachate and solid waste are not effective from an economic, environmental, and social standpoint. The present study assesses the potential of the bioelectrochemical system (BES) integrated with sulfate-reducing bacteria (SRB) in the sustainable treatment and decontamination of landfill wastes. For this purpose, solid waste and landfill leachate collected from different landfill sites were evaluated for long-term treatment using the integrated SRB-BES anaerobic designed bioreactors after pre-treatment. Based on periodic gas composition analysis, physicochemical characterization of the leachate and solid waste, and metal concentration determination, the present system demonstrated significant improvement in volumetric hydrogen production by suppressing methanogenesis. High reduction percentages of Be, Cr, Pb, Cd, Sb, Ni, Cr, COD, and sTOC removal were observed. This mineralization can be attributed to the synergistic effect of ammonia-assisted pre-treatment complexation and microbial sulphide formation. Despite being amended with 0.1N ammonia, the treated leachate level of NO³⁻ was found to be reduced along with SO₄²⁻. This integrated SRB-BES system can be recommended as an eco-friendly solution for landfill reclamation. The BES-treated solid waste was evidently more stabilized, as shown by a five-fold increase in surface area, and potentially useful for leachate immobilization and bio-fortification of agricultural fields. The vector arrangement and magnitude showed similar treatment with differences in magnitudes for both leachate and solid waste. These findings support the efficacy of SRB-BES in the treatment of landfill leachate and solid waste sustainably, inching a step closer to our sustainable development goals. It utilizes low-cost treatment, and anaerobic SRB adapted to landfill sites. This technology may prove to be a sustainable treatment strategy upon scaling up as its outcomes are two-pronged: landfill waste treatment and energy recovery.

Keywords: bio-electrochemical system, leachate /solid waste treatment, landfill leachate, sulfate-reducing bacteria

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34 Assessment of Heavy Metal Concentrations in Tunas Caught from Lakshweep Islands, India

Authors: Mahesh Kumar Farejiya, Anil Kumar Dikshit

Abstract:

The toxic metal contamination and their biomagnification in marine fishes is a serious public health concern specially, in the coastal areas and the small islands. In the present study, concentration of toxic heavy metals like zinc (Zn), cadmium (Cd), lead (Pb), nickel (Ni), cobalt (Co), chromium (Cr) and mercury (Hg) were determined in the tissues of tunas (T. albacores) caught from the area near to Lakshdweep Islands. The heavy metals are one of the indicators for the marine water pollution. Geochemical weathering, industrialization, agriculture run off, fishing, shipping and oil spills are the major pollutants. The presence of heavy toxic metals in the near coastal water fishes at both western coast and eastern coast of India has been well established. The present study was conducted assuming that the distant island will not have the metals presence in a way it is at the near main land coast. However, our study shows that there is a significant amount of the toxic metals present in the tissues of tuna samples. The gill, lever and flash samples were collected in waters around Lakshdweep Islands. They were analyzed using ICP–AES for the toxic metals after microwave digestion. The concentrations of the toxic metals were found in all fish samples and the general trend of presence was in decreasing order as Zn > Al > Cd > Pb > Cr > Ni > Hg. The amount of metals was found to higher in fish having more weight.

Keywords: toxic metals, marine tuna fish, bioaccumulation, biomagnifications

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33 Simulation of the Flow in Bilayer Coextrusion Dies with Gradually Changing Calibrator Profiles

Authors: Mahesh Gupta

Abstract:

The main goal in the design of a die for extrusion of a complex profile is to obtain a uniform velocity at the die exit. If the velocity at the exit of an extrusion die is not uniform, the shape of the extrudate profile can change significantly after the polymer exits the die. To rectify the extrudate distortion caused by non-uniform exit velocity, calibrators and sizers are often installed along the extrudate cooling system. Furthermore, the profile shape in calibrators and sizers is sometimes gradually changed to intentionally deform the extrudate to the required final product shape. This is exploited to simplify extrusion die design, because a relatively simple profile at the die exit can be modified to obtain a more complex profile by deforming it in calibrators or sizers. The gradual change in the shape of calibrator or sizer profiles can also be used to extrude slightly different profiles from the same die. In the present work, a combined flow, thermal and structural analysis is used to accurately predict distortion of extrudate profile after the polymer leaves a die. Simulations of the flow and extrudate deformation in two different bilayer coextrusion dies with gradually changing profile shape in successive calibrators and sizers will be presented. The effect of non-uniform exit velocity, cooling shrinkage and shape of sizer profiles on extrudate deformation is included in the simulation. The predicted extrudate shape and layer structure is found to match accurately with those in a coextruded product.

Keywords: coextrusion, extrusion die design, finite element method, polymers

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32 Identification and Characterization of Enterobacter cloacae, New Soft Rot Causing Pathogen of Radish in India

Authors: B. S. Chandrashekar, M. K. Prasannakumar, P. Buela Parivallal, Sahana N. Banakar, Swathi S. Patil, H. B. Mahesh, D. Pramesh

Abstract:

Bacterial soft rot is one of the most often seen diseases in many plant species globally, resulting in considerable yield loss. Radish roots with dark water-soaked lesions, maceration of tissue, and a foul odour were collected in the Kolar region, India. Two isolates were obtained from rotted samples that demonstrated morphologically unpigmented, white mucoid convex colonies on nutrient agar medium. The isolated bacteria (RDH1 and RDH3) were gram-negative, rod-shaped bacteria with biochemically distinct characteristics similar to the type culture of Enterobacter cloacae ATCC13047 and Bergy's handbook of determinative bacteriology. The 16s rRNA gene was used to identify Enterobacter species. On carrot, potato, tomato, chilli, bell pepper, knolkhol, cauliflower, cabbage, and cucumber slices, the Koch′s postulates were fulfilled, and the pathogen was also pathogenic on radish, cauliflower, and cabbage seedlings were grown in a glasshouse. After 36 hours, both isolates exhibited a hypersensitive sensitivity to Nicotianatabacum. Semi-quantitative analysis revealed that cell wall degrading enzymes (CWDEs) such as pectin lyase, polygalacturonase, and cellulase (p=1.4e09) contributed to pathogenicity, whereas isolates produced biofilms (p=4.3e-11) that help in host adhesion. This is the first report in India of radish soft rot caused by E. cloacae.

Keywords: soft rot, enterobacter cloacae, 16S rRNA, nicotiana tabacum, and pathogenicity

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31 Phyto-Assisted Synthesis of Magnesium Oxide Nanoparticles: Characterization and Applications

Authors: Surendra Kumar Gautam, Mahesh Dhungana

Abstract:

Magnesium oxide nanoparticles (MgO NPs) are less toxic to humans and the environment as compared to other metal oxide nanoparticles. Various conventional chemical and physical methods are used for synthesis whose toxicity level is high and highly expensive. As the best alternative, phyto-assisted synthesis has emerged, which uses extracts from plant parts for the synthesis of nanoparticles. Here, we report the synthesis of MgO nanoparticles with the assistance of beetroot extract and leaf extract of P. guajava and A. adenophora. The synthesized MgO NPs were characterized by X-ray diffraction (XRD), Fourier transforms infrared spectroscopy (FTIR), and UV-visible spectroscopy. X-ray analysis for the broadening of peaks was used to evaluate the crystallite size and lattice strain using Debye-Scherer and Williamson–Hall method. The results of crystallite size obtained by both methods are in close proximity. The crystallite size obtained by the Williamson-Hall method seems more accurate, with values being 8.1 nm and 13.2 nm for beetroot MgO NPs and P. guajava MgO NPs, respectively. The FT-IR spectroscopy revealed the dominance of chemical bonds as well as functional groups on MgO NPs surfaces. The UV-visible absorption spectra of MgO NPs were found to be 310 nm, 315 nm, and 315 nm for beetroot, P. guajava, and A. adenophora leaf extract, respectively. Among the three samples, beetroot-mediated MgO NPs were effective antibacterial against both gram-positive and Gram-negative bacteria. In addition, synthesized MgO NPs also show significant antioxidant efficacy against 1,1-diphenyl-2-picrylhydrazyl radical. Further, beetroot MgO NPs showed the highest photocatalytic activity of about 91% in comparison with other samples.

Keywords: MgO NPs, XRD, FTIR, antibacterial, antioxidant and photocatalytic activity

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30 Environmental Effects on Coconut Coir Fiber Epoxy Composites Having TiO₂ as Filler

Authors: Srikanth Korla, Mahesh Sharnangat

Abstract:

Composite materials are being widely used in Aerospace, Naval, Defence and other branches of engineering applications. Studies on natural fibers is another emerging research area as they are available in abundance, and also due to their eco-friendly in nature. India being one of the major producer of coir, there is always a scope to study the possibilities of exploring coir as reinforment, and with different combinations of other elements of the composite. In present investigation effort is made to utilize properties possessed by natural fiber and make them enable with polymer/epoxy resin. In natural fiber coconut coir is used as reinforcement fiber in epoxy resin with varying weight percentages of fiber and filler material. Titanium dioxide powder (TiO2) is used as filler material with varying weight percentage including 0%, 2% and 4% are considered for experimentation. Environmental effects on the performance of the composite plate are also studied and presented in this project work; Moisture absorption test for composite specimens is conducted using different solvents including Kerosene, Mineral Water and Saline Water, and its absorption capacity is evaluated. Analysis is carried out in different combinations of Coir as fiber and TiO2 as filler material, and the best suitable composite material considering the strength and environmental effects is identified in this work. Therefore, the significant combination of the composite material is with following composition: 2% TiO2 powder 15% of coir fibre and 83% epoxy, under unique mechanical and environmental conditions considered in the work.

Keywords: composite materials, moisture test, filler material, natural fibre composites

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29 Prognosis of Patients with COVID-19 and Hematologic Malignancies

Authors: Elizabeth Behrens, Anne Timmermann, Alexander Yerkan, Joshua Thomas, Deborah Katz, Agne Paner, Melissa Larson, Shivi Jain, Seo-Hyun Kim, Celalettin Ustun, Ankur Varma, Parameswaran Venugopal, Jamile Shammo

Abstract:

Coronavirus Disease-2019 (COVID-19) causes persistent concern for poor outcomes in vulnerable populations. Patients with hematologic malignancies (HM) have been found to have higher COVID-19 case fatality rates compared to those without malignancy. While cytopenias are common in patients with HM, especially in those undergoing chemotherapy treatment, hemoglobin (Hgb) and platelet count have not yet been studied, to our best knowledge, as potential prognostic indicators for patients with HM and COVID-19. The goal of this study is to identify factors that may increase the risk of mortality in patients with HM and COVID-19. In this single-center, retrospective, observational study, 65 patients with HM and laboratory confirmed COVID-19 were identified between March 2020 and January 2021. Information on demographics, laboratory data the day of COVID-19 diagnosis, and prognosis was extracted from the electronic medical record (EMR), chart reviewed, and analyzed using the statistical software SAS version 9.4. Chi-square testing was used for categorical variable analyses. Risk factors associated with mortality were established by logistic regression models. Non-Hodgkin lymphoma (37%), chronic lymphocytic leukemia (20%), and plasma cell dyscrasia (15%) were the most common HM. Higher Hgb level upon COVID-19 diagnosis was related to decreased mortality, odd ratio=0.704 (95% confidence interval [CI]: 0.511-0.969; P = .0263). Platelet count the day of COVID-19 diagnosis was lower in patients who ultimately died (mean 127 ± 72K/uL, n=10) compared to patients who survived (mean 197 ±92K/uL, n=55) (P=.0258). Female sex was related to decreased mortality, odd ratio=0.143 (95% confidence interval [CI]: 0.026-0.785; P = .0353). There was no mortality difference between the patients who were on treatment for HM the day of COVID-19 diagnosis compared to those who were not (P=1.000). Lower Hgb and male sex are independent risk factors associated with increased mortality of HM patients with COVID-19. Clinicians should be especially attentive to patients with HM and COVID-19 who present with cytopenias. Larger multi-center studies are urgently needed to further investigate the impact of anemia, thrombocytopenia, and demographics on outcomes of patients with hematologic malignancies diagnosed with COVID-19.

Keywords: anemia, COVID-19, hematologic malignancy, prognosis

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28 A Precision Medicine Approach to Sickle Cell Disease by Targeting the Adhesion Interactome

Authors: Anthara Vivek, Manisha Shukla, Mahesh Narayan, Prakash Narayan

Abstract:

Sickle cell disease disproportionately affects sub-Saharan Africa and certain tribal populaces in India and has consequently drawn little intertest from Pharma. In sickle cell patients, adhesion of erythrocytes or reticulocytes to one another and the vessel wall results in painful ischemic episodes with few, if any, effective treatments for vaso-occlusive crises. Identification of disease-associated adhesion markers on erythrocytes or reticulocytes might inform the use of more effective therapies against vaso-occlusive crises. Increased expression of one or more of bcam, itga4, cd44, cd47, rap1a, vcam1, or icam4 has been reported in sickle cell subjects. Using the miRNet ontology knowledgebase, peripheral blood interactomes were generated by seeding various combinations of the afore-referenced mRNA. These interactomes yielded an array of miR targets. As examples, targeting hsa-miR-155-5p can potentially neutralize the rap1a-bcam-cd44-itga4-vcam1 erythrocyte/reticulocyte adhesion interactome whereas targeting hsa-miRs-103a-3p or 107 can potentially neutralize adhesion in cells overexpressing icam4-cd47-bcam-itga4-cd36. AM3380 (MIRacle™) is an off-the shelf hsa-miR-155-5p agomiR that can potentially neutralize the rap1a-bcam-cd44-itga4-vcam1 signaling axis. Phlebotomy coupled with transcriptomics represents a potentially feasible and effective precision medicine strategy to mitigate vaso-occlusive crises in sickle cell patients.

Keywords: adhesion, interactome, precision, medicine

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27 Effect of Gas Boundary Layer on the Stability of a Radially Expanding Liquid Sheet

Authors: Soumya Kedia, Puja Agarwala, Mahesh Tirumkudulu

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Linear stability analysis is performed for a radially expanding liquid sheet in the presence of a gas medium. A liquid sheet can break up because of the aerodynamic effect as well as its thinning. However, the study of the aforementioned effects is usually done separately as the formulation becomes complicated and is difficult to solve. Present work combines both, aerodynamic effect and thinning effect, ignoring the non-linearity in the system. This is done by taking into account the formation of the gas boundary layer whilst neglecting viscosity in the liquid phase. Axisymmetric flow is assumed for simplicity. Base state analysis results in a Blasius-type system which can be solved numerically. Perturbation theory is then applied to study the stability of the liquid sheet, where the gas-liquid interface is subjected to small deformations. The linear model derived here can be applied to investigate the instability for sinuous as well as varicose modes, where the former represents displacement in the centerline of the sheet and the latter represents modulation in sheet thickness. Temporal instability analysis is performed for sinuous modes, which are significantly more unstable than varicose modes, for a fixed radial distance implying local stability analysis. The growth rates, measured for fixed wavenumbers, predicated by the present model are significantly lower than those obtained by the inviscid Kelvin-Helmholtz instability and compare better with experimental results. Thus, the present theory gives better insight into understanding the stability of a thin liquid sheet.

Keywords: boundary layer, gas-liquid interface, linear stability, thin liquid sheet

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26 Switching Studies on Ge15In5Te56Ag24 Thin Films

Authors: Diptoshi Roy, G. Sreevidya Varma, S. Asokan, Chandasree Das

Abstract:

Germanium Telluride based quaternary thin film switching devices with composition Ge15In5Te56Ag24, have been deposited in sandwich geometry on glass substrate with aluminum as top and bottom electrodes. The bulk glassy form of the said composition is prepared by melt quenching technique. In this technique, appropriate quantity of elements with high purity are taken in a quartz ampoule and sealed under a vacuum of 10-5 mbar. Then, it is allowed to rotate in a horizontal rotary furnace for 36 hours to ensure homogeneity of the melt. After that, the ampoule is quenched into a mixture of ice - water and NaOH to get the bulk ingot of the sample. The sample is then coated on a glass substrate using flash evaporation technique at a vacuum level of 10-6 mbar. The XRD report reveals the amorphous nature of the thin film sample and Energy - Dispersive X-ray Analysis (EDAX) confirms that the film retains the same chemical composition as that of the base sample. Electrical switching behavior of the device is studied with the help of Keithley (2410c) source-measure unit interfaced with Lab VIEW 7 (National Instruments). Switching studies, mainly SET (changing the state of the material from amorphous to crystalline) operation is conducted on the thin film form of the sample. This device is found to manifest memory switching as the device remains 'ON' even after the removal of the electric field. Also it is found that amorphous Ge15In5Te56Ag24 thin film unveils clean memory type of electrical switching behavior which can be justified by the absence of fluctuation in the I-V characteristics. The I-V characteristic also reveals that the switching is faster in this sample as no data points could be seen in the negative resistance region during the transition to on state and this leads to the conclusion of fast phase change during SET process. Scanning Electron Microscopy (SEM) studies are performed on the chosen sample to study the structural changes at the time of switching. SEM studies on the switched Ge15In5Te56Ag24 sample has shown some morphological changes at the place of switching wherein it can be explained that a conducting crystalline channel is formed in the device when the device switches from high resistance to low resistance state. From these studies it can be concluded that the material may find its application in fast switching Non-Volatile Phase Change Memory (PCM) Devices.

Keywords: Chalcogenides, Vapor deposition, Electrical switching, PCM.

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25 Fungal Diversity and Bioprospecting of Termite-Associated Fungi from Nothern-Western Ghats of India

Authors: Gajanan V. Mane, Rashmi More, Mahesh S. Sonawane, Tushar Lodha, Rohit Sharma

Abstract:

The diversity of fungi isolated from two different termite species viz., Odontoterms assmuthi and O. abesus was investigated by dilution- plate method, combined with morphological characteristics and sequencing of internal transcribed spacer region. In total, ninety-six fungi were isolated and purified, out of which 69 isolates were obtained from O. assmuthi belonging to 18 genera and 31 species, whereas 27 isolates were obtained from O. abesus belonging to 15 genera and 17 species. The fungal strains were screened for laccase, amylase, cellulase and pectinase enzymes production. Twenty-seven strains were positive for laccase, 59 strains were positive for amylase, 71 strains were positive for cellulase and 72 strains were positive for pectinase enzymes. The antimicrobial activities of the isolated fungi were tested by the dual plate culture method against standard pathogens. Bioactive secondary metabolites were identified by HPLC and LCMS. Four isolates viz., Penicillium goetzii MG 57, Epicoccum sp. MG 39, Penicillium tanzanicum MG 30, Aspergillus polyporicola MG 54, showed positive antimicrobial activity against standard pathogens, Streptococcus pneumonia MCC 2425, Staphylococcus aureus MCC 2408, Pseudomonas aeruginosa MCC 2080, Escherichia coli MCC 2412, Enterococcus faecalis MCC 2409, Klebsiella pneumonia MCC 2451, Micrococcus luteus MCC 2155 and Candida albicans MCC 1151. In conclusion, the study showed that the insect gut harbor fungal diversity, which is futuristic with biotechnological potential and could be a good source of enzymes and antibiotics.

Keywords: termites, fungi, its, enzyme, antimicrobial activity

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24 Insights and Observation for Optimum Work Roll Cooling in Flat Hot Mills: A Case Study on Shape Defect Elimination

Authors: Uday S. Goel, G. Senthil Kumar, Biswajit Ghosh, V. V. Mahashabde, Dhirendra Kumar, H. Manjunath, Ritesh Kumar, Mahesh Bhagwat, Subodh Pandey

Abstract:

Tata Steel Bhushan Steel Ltd.(TSBSL)’s Hot Mill at Angul , Orissa , India, was facing shape issues in Hot Rolled (HR) coils. This was resulting in a defect called as ‘Ridge’, which was appearing in subsequent cold rolling operations at various cold mills (CRM) and external customers. A collaborative project was undertaken to resolve this issue. One of the reasons identified was the strange drop in thermal crown after rolling of 20-25 coils in the finishing mill (FM ) schedule. On the shop floor, it was observed that work roll temperatures in the FM after rolling were very high and non uniform across the work roll barrel. Jammed work roll cooling nozzles, insufficient roll bite lubrication and inadequate roll cooling water quality were found to be the main reasons. Regular checking was initiated to check roll cooling nozzles health, and quick replacement done if found jammed was implemented. Improvements on roll lubrication, especially flow rates, was done. Usage of anti-peeling headers and inter stand descaling was enhanced. A subsequent project was also taken up for improving the quality of roll cooling water. Encouraging results were obtained from the project with a reduction in rejection due to ridge at CRM’s by almost 95% of the pre project start levels. Poor profile occurrence of HR coils at HSM was also reduced from a high of 32% in May’19 to <1% since Apr’20.

Keywords: hot rolling flat, shape, ridge, work roll, roll cooling nozzle, lubrication

Procedia PDF Downloads 56
23 Contribution of NLRP3 Inflammasome to the Protective Effect of 5,14-HEDGE, A 20-HETE Mimetic, against LPS-Induced Septic Shock in Rats

Authors: Bahar Tunctan, Sefika Pinar Kucukkavruk, Meryem Temiz-Resitoglu, Demet Sinem Guden, Ayse Nihal Sari, Seyhan Sahan-Firat, Mahesh P. Paudyal, John R. Falck, Kafait U. Malik

Abstract:

We hypothesized that 20-hydroxyeicosatetraenoic acid (20-HETE) mimetics such as N-(20-hydroxyeicosa-5[Z],14[Z]-dienoyl)glycine (5,14-HEDGE) may be beneficial for preventing mortality due to inflammation induced by lipopolysaccharide (LPS). This study aims to assess the effect of 5,14-HEDGE on the LPS-induced changes in nucleotide binding domain and leucine-rich repeat protein 3 (NLRP3)/apoptosis-associated speck-like protein containing a caspase activation and recruitment domain (ASC)/pro-caspase-1 inflammasome. Rats were injected with saline (4 ml/kg) or LPS (10 mg/kg) at time 0. Blood pressure and heart rate were measured using a tail-cuff device. 5,14-HEDGE (30 mg/kg) was administered to rats 1 h after injection of saline or LPS. The rats were sacrificed 4 h after saline or LPS injection and kidney, heart, thoracic aorta, and superior mesenteric artery were isolated for measurement of caspase-1/11 p20, NLRP3, ASC, and β-actin proteins as well as interleukin-1β (IL-1β) levels. Blood pressure decreased by 33 mmHg and heart rate increased by 63 bpm in the LPS-treated rats. In the LPS-treated rats, tissue protein expression of caspase-1/11 p20, NLRP3, and ASC in addition to IL-1β levels were increased. 5,14-HEDGE prevented the LPS-induced changes. Our findings suggest that inhibition of renal, cardiac, and vascular formation/activity of NLRP3/ASC/pro-caspase-1 inflammasome involved in the protective effect of 5,14-HEDGE on LPS-induced septic shock in rats. This work was financially supported by the Mersin University (2015-AP3-1343) and USPHS NIH (PO1 HL034300).

Keywords: 5, 14-HEDGE, lipopolysaccharide, NLRP3, inflammasome, septic shock

Procedia PDF Downloads 270
22 Assessment of Land Use Land Cover Change-Induced Climatic Effects

Authors: Mahesh K. Jat, Ankan Jana, Mahender Choudhary

Abstract:

Rapid population and economic growth resulted in changes in large-scale land use land cover (LULC) changes. Changes in the biophysical properties of the Earth's surface and its impact on climate are of primary concern nowadays. Different approaches, ranging from location-based relationships or modelling earth surface - atmospheric interaction through modelling techniques like surface energy balance (SEB) are used in the recent past to examine the relationship between changes in Earth surface land cover and climatic characteristics like temperature and precipitation. A remote sensing-based model i.e., Surface Energy Balance Algorithm for Land (SEBAL), has been used to estimate the surface heat fluxes over Mahi Bajaj Sagar catchment (India) from 2001 to 2020. Landsat ETM and OLI satellite data are used to model the SEB of the area. Changes in observed precipitation and temperature, obtained from India Meteorological Department (IMD) have been correlated with changes in surface heat fluxes to understand the relative contributions of LULC change in changing these climatic variables. Results indicate a noticeable impact of LULC changes on climatic variables, which are aligned with respective changes in SEB components. Results suggest that precipitation increases at a rate of 20 mm/year. The maximum and minimum temperature decreases and increases at 0.007 ℃ /year and 0.02 ℃ /year, respectively. The average temperature increases at 0.009 ℃ /year. Changes in latent heat flux and sensible heat flux positively correlate with precipitation and temperature, respectively. Variation in surface heat fluxes influences the climate parameters and is an adequate reason for climate change. So, SEB modelling is helpful to understand the LULC change and its impact on climate.

Keywords: LULC, sensible heat flux, latent heat flux, SEBAL, landsat, precipitation, temperature

Procedia PDF Downloads 90
21 Antioxidant, Antibacterial and Functional Group Analysis of Ethanolic Extract of Hylocereus undatus and Garcinia indica by Using Fourier Transform Infrared Spectroscopy

Authors: Ajay Krishnamurthy, Mariyappan Mahesh Kumar, Sellamuthu Periyar Selvam

Abstract:

Fruits are considered as functional foods due to the presence of various bioactive compounds available such as polyphenols, which are beneficial to health when consumed as part of our diet. The primary objective of this study was to analyze the various functional groups present in ethanolic extracts of Hylocereus undatus and Garcinia indica and also measure their antibacterial and antioxidant potential respectively thereby affirming its nutraceutical potential. To fulfill our objective, a Fourier - transform Infrared Spectroscopy (FTIR) was conducted for functional group analysis, Total Phenolic Content and DPPH free radical scavenging activity for measuring it anti-oxidant potential and agar-well diffusion assay for antibacterial potential. On careful observation and analysis of the spectrum it was found that both the fruit extracts contain similar compounds viz. Phenols, Alkanes, Alkenes, Aldehydes, Ketones, Carboxylic Acid and Amines. Total phenolic content of H.undatus and G.indica was estimated to be (26.85 ± 1.84 mg GAE/100g) and (32.84 ± 1.63 mg GAE/100g) respectively which corresponds to an inhibition of 84% and 81% respectively. H.undatus shows an inhibition of (3.4 ± 2.1mm) in gram-positive and (4.2 ± 2.24mm) in gram-negative organism on the other hand G.indica shows (2.1 ± 0.98mm) in gram-positive and (3.1 ± 1.44mm) in gram negative. The presence of such diverse compounds in the fruits helps us to understand the necessity for the inclusion of fruits in our daily diet and also helps the pharmaceutical industry in realizing the importance of exotic fruits as a potential nutraceutical.

Keywords: DPPH, fourier-transform infrared spectroscopy (FTIR), Hylocereus undatus, Garcinia indica

Procedia PDF Downloads 150
20 Comparati̇ve Study of Pi̇xel and Object-Based Image Classificati̇on Techni̇ques for Extracti̇on of Land Use/Land Cover Informati̇on

Authors: Mahesh Kumar Jat, Manisha Choudhary

Abstract:

Rapid population and economic growth resulted in changes in large-scale land use land cover (LULC) changes. Changes in the biophysical properties of the Earth's surface and its impact on climate are of primary concern nowadays. Different approaches, ranging from location-based relationships or modelling earth surface - atmospheric interaction through modelling techniques like surface energy balance (SEB) have been used in the recent past to examine the relationship between changes in Earth surface land cover and climatic characteristics like temperature and precipitation. A remote sensing-based model i.e., Surface Energy Balance Algorithm for Land (SEBAL), has been used to estimate the surface heat fluxes over Mahi Bajaj Sagar catchment (India) from 2001 to 2020. Landsat ETM and OLI satellite data are used to model the SEB of the area. Changes in observed precipitation and temperature, obtained from India Meteorological Department (IMD) have been correlated with changes in surface heat fluxes to understand the relative contributions of LULC change in changing these climatic variables. Results indicate a noticeable impact of LULC changes on climatic variables, which are aligned with respective changes in SEB components. Results suggest that precipitation increases at a rate of 20 mm/year. The maximum and minimum temperature decreases and increases at 0.007 ℃ /year and 0.02 ℃ /year, respectively. The average temperature increases at 0.009 ℃ /year. Changes in latent heat flux and sensible heat flux positively correlate with precipitation and temperature, respectively. Variation in surface heat fluxes influences the climate parameters and is an adequate reason for climate change. So, SEB modelling is helpful to understand the LULC change and its impact on climate.

Keywords: remote sensing, GIS, object based, classification

Procedia PDF Downloads 92
19 Action Potential of Lateral Geniculate Neurons at Low Threshold Currents: Simulation Study

Authors: Faris Tarlochan, Siva Mahesh Tangutooru

Abstract:

Lateral Geniculate Nucleus (LGN) is the relay center in the visual pathway as it receives most of the input information from retinal ganglion cells (RGC) and sends to visual cortex. Low threshold calcium currents (IT) at the membrane are the unique indicator to characterize this firing functionality of the LGN neurons gained by the RGC input. According to the LGN functional requirements such as functional mapping of RGC to LGN, the morphologies of the LGN neurons were developed. During the neurological disorders like glaucoma, the mapping between RGC and LGN is disconnected and hence stimulating LGN electrically using deep brain electrodes can restore the functionalities of LGN. A computational model was developed for simulating the LGN neurons with three predominant morphologies, each representing different functional mapping of RGC to LGN. The firings of action potentials at LGN neuron due to IT were characterized by varying the stimulation parameters, morphological parameters and orientation. A wide range of stimulation parameters (stimulus amplitude, duration and frequency) represents the various strengths of the electrical stimulation with different morphological parameters (soma size, dendrites size and structure). The orientation (0-1800) of LGN neuron with respect to the stimulating electrode represents the angle at which the extracellular deep brain stimulation towards LGN neuron is performed. A reduced dendrite structure was used in the model using Bush–Sejnowski algorithm to decrease the computational time while conserving its input resistance and total surface area. The major finding is that an input potential of 0.4 V is required to produce the action potential in the LGN neuron which is placed at 100 µm distance from the electrode. From this study, it can be concluded that the neuroprostheses under design would need to consider the capability of inducing at least 0.4V to produce action potentials in LGN.

Keywords: Lateral Geniculate Nucleus, visual cortex, finite element, glaucoma, neuroprostheses

Procedia PDF Downloads 251
18 Efficient Video Compression Technique Using Convolutional Neural Networks and Generative Adversarial Network

Authors: P. Karthick, K. Mahesh

Abstract:

Video has become an increasingly significant component of our digital everyday contact. With the advancement of greater contents and shows of the resolution, its significant volume poses serious obstacles to the objective of receiving, distributing, compressing, and revealing video content of high quality. In this paper, we propose the primary beginning to complete a deep video compression model that jointly upgrades all video compression components. The video compression method involves splitting the video into frames, comparing the images using convolutional neural networks (CNN) to remove duplicates, repeating the single image instead of the duplicate images by recognizing and detecting minute changes using generative adversarial network (GAN) and recorded with long short-term memory (LSTM). Instead of the complete image, the small changes generated using GAN are substituted, which helps in frame level compression. Pixel wise comparison is performed using K-nearest neighbours (KNN) over the frame, clustered with K-means, and singular value decomposition (SVD) is applied for each and every frame in the video for all three color channels [Red, Green, Blue] to decrease the dimension of the utility matrix [R, G, B] by extracting its latent factors. Video frames are packed with parameters with the aid of a codec and converted to video format, and the results are compared with the original video. Repeated experiments on several videos with different sizes, duration, frames per second (FPS), and quality results demonstrate a significant resampling rate. On average, the result produced had approximately a 10% deviation in quality and more than 50% in size when compared with the original video.

Keywords: video compression, K-means clustering, convolutional neural network, generative adversarial network, singular value decomposition, pixel visualization, stochastic gradient descent, frame per second extraction, RGB channel extraction, self-detection and deciding system

Procedia PDF Downloads 161
17 Anti-Obesity Activity of Garcinia xanthochymus: Biochemical Characterization and In vivo Studies in High Fat Diet-Rat Model

Authors: Mahesh M. Patil, K. A. Anu-Appaiah

Abstract:

Overweight and obesity is a serious medical problem, increasing in prevalence, and affecting millions worldwide. Investigators have been trying from decades to articulate the burden of obesity and related risk factors. To answer this problem, we suggest a new therapeutic anti-obesity compounds from Garcinia xanthochymus fruit. However, there is little published scientific information on non-hydroxycitric acid Garcinia species. Our findings include biochemical characterization of the fruit; in vivo toxicity and bio-efficacy study of G. xanthochymus in high fat diet wistar rat model. We observed that Garcinia pericarp is a rich source of organic acids, polyphenols, mono- (40.63%) and poly-unsaturated fatty acids (16.45%; omega-3: 10.02%). Toxicological studies have showed that Garcinia is safe and had no observed adverse effect level up to 400 mg/kg/day. Body weight and food intake was significantly (P<0.05) reduced in oral gavage treated rats (sonicated Garcinia powder) in 13 weeks. Subcutaneous fat was significantly (P<0.05) reduced in Garcinia treated rats. Hepatocytes significantly (p<0.05) overexpressed sterol regulatory element binding protein 2, liver X receptor- α, liver X receptor- β, lipoprotein lipase and monoacylglycerol lipase. Fatty acid binding protein 1 and peroxisome proliferator activated receptor- α were down regulated as assessed by real time qPCR. Currently our research is focused on the adipocyte obesity related gene expressions, effect of Garcinia on 3T3-adipocyte cell lines and high fat diet induced mice model. This in vivo pre-clinical data suggests that G. xanthochymus may have clinical utility for the treatment of obesity. However, further studies are required to establish its potency.

Keywords: Garcinia xanthochymus, anti-obesity, high fat diet, real time qPCR

Procedia PDF Downloads 230
16 Consumers Perception of Slogans/ Taglines: A Study of Higher Education Sector in India

Authors: Puja Mahesh

Abstract:

Purpose: A good slogan captures the essence of your brand's promised consumer benefit in one short phrase. A good slogan conjures up positive imagery about your business or your product. A good slogan has the element of immediacy. Immediacy does not necessarily mean that the slogan will inspire consumers to run right out and buy your product. It does mean, however, that your slogan has an immediate cognitive impact. It forces your audience to "stop-and-think" after exposure as a necessary first step toward remembering your slogan promise. A good slogan is memorable and durability. When your slogan promise is occupying prime real estate in the consumer's subconscious, it aids in recall and activates preference for your brand when you want it -when consumers are ready to buy. The objective of current study is to understand the consumer perception of slogans/taglines of higher education sector in India. Design/Methodology/Approach: Survey of 500 consumers (largely comprising of youth) will be done using questionnaire. Universities and institutes will be chosen on the basis of various streams and Credible Rankings. The perception will be taken from the respondents on the basis of scale. Findings: Catchy phrases, rhymes, music, jingles, avatars (visual representations) and unique imagery are just a few of the mnemonic clutter-busting tactics commonly used in slogans to stand apart from the competition and to aid in memory recall. The study will reveal whether it is true that catchy phrases, rhymes, music, jingles, avatars (visual representations) and unique imagery across disciplines and universities help in building stronger brands. It will also be found whether consumers pay more attention to reputation of University/ College or brand identity. Originality/Value: Researcher has not come across any study of Consumer Perception of Slogans/Taglines of Higher Education Brands in India. Also, it would be interesting to understand Consumer Perception of various colleges/streams particularly Management colleges who invest a lot of time in branding exercise.

Keywords: consumer perception, higher education, slogans, taglines

Procedia PDF Downloads 385
15 Comparison of Multivariate Adaptive Regression Splines and Random Forest Regression in Predicting Forced Expiratory Volume in One Second

Authors: P. V. Pramila , V. Mahesh

Abstract:

Pulmonary Function Tests are important non-invasive diagnostic tests to assess respiratory impairments and provides quantifiable measures of lung function. Spirometry is the most frequently used measure of lung function and plays an essential role in the diagnosis and management of pulmonary diseases. However, the test requires considerable patient effort and cooperation, markedly related to the age of patients esulting in incomplete data sets. This paper presents, a nonlinear model built using Multivariate adaptive regression splines and Random forest regression model to predict the missing spirometric features. Random forest based feature selection is used to enhance both the generalization capability and the model interpretability. In the present study, flow-volume data are recorded for N= 198 subjects. The ranked order of feature importance index calculated by the random forests model shows that the spirometric features FVC, FEF 25, PEF,FEF 25-75, FEF50, and the demographic parameter height are the important descriptors. A comparison of performance assessment of both models prove that, the prediction ability of MARS with the `top two ranked features namely the FVC and FEF 25 is higher, yielding a model fit of R2= 0.96 and R2= 0.99 for normal and abnormal subjects. The Root Mean Square Error analysis of the RF model and the MARS model also shows that the latter is capable of predicting the missing values of FEV1 with a notably lower error value of 0.0191 (normal subjects) and 0.0106 (abnormal subjects). It is concluded that combining feature selection with a prediction model provides a minimum subset of predominant features to train the model, yielding better prediction performance. This analysis can assist clinicians with a intelligence support system in the medical diagnosis and improvement of clinical care.

Keywords: FEV, multivariate adaptive regression splines pulmonary function test, random forest

Procedia PDF Downloads 276
14 Polymeric Micelles Based on Block Copolymer α-Tocopherol Succinate-g-Carboxymethyl Chitosan for Tamoxifen Delivery

Authors: Sunil K. Jena, Sanjaya K. Samal, Mahesh Chand, Abhay T. Sangamwar

Abstract:

Tamoxifen (TMX) and its analogues are approved as a first line therapy for the treatment of estrogen receptor-positive tumors. However, clinical development of TMX has been hampered by its low bioavailability and severe hepatotoxicity. Herein, we attempt to design a new drug delivery vehicle that could enhance the pharmacokinetic performance of TMX. Initially, high-molecular weight carboxymethyl chitosan was hydrolyzed to low-molecular weight carboxymethyl chitosan (LMW CMC) with hydrogen peroxide under the catalysis of phosphotungstic acid. Amphiphilic block copolymers of LMW CMC were synthesized via amidation reaction between the carboxyl group of α-tocopherol succinate (TS) and an amine group of LMW CMC. These amphiphilic block copolymers were self-assembled to nanosize core-shell-structural micelles in the aqueous medium. The critical micelle concentration (CMC) decreased with the increasing substitution of TS on LMW CMC, which ranged from 1.58 × 10-6 to 7.94 × 10-8 g/mL. Maximum TMX loading up to 8.08 ± 0.98% was achieved with Cmc-TS4.5 (TMX/Cmc-TS4.5 with 1:8 weight ratio). Both blank and TMX-loaded polymeric micelles (TMX-PM) of Cmc-TS4.5 exhibits spherical shape with the particle size below 200 nm. TMX-PM has been found to be stable in the gastrointestinal conditions and released only 44.5% of the total drug content by the first 72 h in simulated gastric fluid (SGF), pH 1.2. However, the presence of pepsin does not significantly increased the TMX release in SGF, pH 1.2, released only about 46.2% by the first 72 h suggesting its inability to cleave the peptide bond. In contrast, the release of TMX from TMX-PM4.5 in SIF, pH 6.8 (without pancreatin) was slow and sustained, released only about 10.43% of the total drug content within the first 30 min and nearly about 12.41% by the first 72 h. The presence of pancreatin in SIF, pH 6.8 led to an improvement in drug release. About 28.09% of incorporated TMX was released in the presence of pancreatin in 72 h. A cytotoxicity study demonstrated that TMX-PM exhibited time-delayed cytotoxicity in human MCF-7 breast cancer cells. Pharmacokinetic studies on Sprague-Dawley rats revealed a remarkable increase in oral bioavailability (1.87-fold) with significant (p < 0.0001) enhancement in AUC0-72 h, t1/2 and MRT of TMX-PM4.5 than that of TMX-suspension. Thus, the results suggested that CMC-TS micelles are a promising carrier for TMX delivery.

Keywords: carboxymethyl chitosan, d-α-tocopherol succinate, pharmacokinetic, polymeric micelles, tamoxifen

Procedia PDF Downloads 309